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Tas E, Flint A, Libman I, Muzumdar R, Ou X, Williams DK, Børsheim E, Diaz EC. The association between hepatic steatosis, vitamin D status, and insulin resistance in adolescents with obesity. OBESITY PILLARS 2025; 14:100173. [PMID: 40206184 PMCID: PMC11979404 DOI: 10.1016/j.obpill.2025.100173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/15/2025] [Accepted: 03/16/2025] [Indexed: 04/11/2025]
Abstract
Introduction Epidemiological studies suggest an inverse relationship between circulating 25-hydroxy-vitamin D [25(OH)D] levels and insulin resistance (IR), yet interventional studies have yielded inconsistent findings. This study examined the relationship between changes in vitamin D status and markers of IR in adolescents, with a focus on the modifying effect of liver fat. Methods A post-hoc analysis was performed using data from 44 adolescents participating in a 6-month observational study evaluating biomarkers of hepatosteatosis. Participants were categorized into two groups based on vitamin D status at the end of the observation period: those whose vitamin D levels increased or remained sufficient (VDI, n = 22) and those whose levels decreased or remained insufficient/deficient (VDD, n = 22). Liver fat percentage was measured using magnetic resonance imaging (MRI) fat-fraction, and IR was assessed using the updated Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR) and the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL). Results Across the cohort, liver fat was positively associated with HOMA2-IR (β = 0.08, p = 0.023). The association between changes in vitamin D status and HOMA2-IR trajectories was modified by liver fat but only in Hispanic adolescents (β = -0.18, p < 0.001). Among Hispanic adolescents in the VDD group, HOMA-IR worsened, particularly at higher levels of liver fat. In non-Hispanic adolescents, HOMA-IR increased in the VDD group (β = 0.65, p = 0.033) compared to the VDI group, independent of baseline liver fat. Across the cohort, changes in vitamin D status interacted with liver fat to influence TG/HDL trajectories (β = 0.20, p = 0.034). Conclusions The metabolic response to changes in vitamin D status in adolescents with IR may vary based on racial and ethnic differences and liver fat status. These findings underscore the importance of considering liver fat and racial/ethnic background in vitamin D and metabolic health studies. Future research with more extensive and diverse cohorts spanning the fatty liver disease spectrum is needed to clarify these relationships.
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Affiliation(s)
- Emir Tas
- UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA
- Center for Childhood Obesity Prevention, Arkansas Children's Research Institute, 13 Children's Way, Little Rock, AR, 72202, USA
| | - Amanda Flint
- UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA
| | - Ingrid Libman
- UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA
| | - Radhika Muzumdar
- UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA
| | - Xiawei Ou
- Arkansas Children's Research Institute, 13 Children's Way, Little Rock, AR, 72202, USA
- Arkansas Children's Nutrition Center, 15 Children's Way, Little Rock, AR, 72202, USA
- Department of Radiology and Pediatrics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR, 72205, USA
| | - David K. Williams
- Arkansas Children's Nutrition Center, 15 Children's Way, Little Rock, AR, 72202, USA
- Department of Biostatistics, University of Arkansas Medical Sciences, 4301 West Markham Street, Little Rock, AR, 72205, USA
| | - Elisabet Børsheim
- Center for Childhood Obesity Prevention, Arkansas Children's Research Institute, 13 Children's Way, Little Rock, AR, 72202, USA
- Arkansas Children's Nutrition Center, 15 Children's Way, Little Rock, AR, 72202, USA
- Department of Pediatrics, University of Arkansas Medical Sciences, 4301 West Markham Street, Little Rock, AR, 72205, USA
| | - Eva C. Diaz
- Center for Childhood Obesity Prevention, Arkansas Children's Research Institute, 13 Children's Way, Little Rock, AR, 72202, USA
- Arkansas Children's Nutrition Center, 15 Children's Way, Little Rock, AR, 72202, USA
- Department of Pediatrics, University of Arkansas Medical Sciences, 4301 West Markham Street, Little Rock, AR, 72205, USA
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Kim NH, Kang JH. Serum 25(OH)D Levels and Risk of Nonalcoholic Fatty Liver Disease in Nonobese and Lean Individuals. Yonsei Med J 2025; 66:269-276. [PMID: 40288898 PMCID: PMC12041399 DOI: 10.3349/ymj.2024.0065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 10/06/2024] [Accepted: 10/08/2024] [Indexed: 04/29/2025] Open
Abstract
PURPOSE The impact of vitamin D deficiency on nonalcoholic fatty liver disease (NAFLD) risk in individuals without obesity or insulin resistance has not been thoroughly evaluated. We aimed to identify whether low serum levels of 25(OH)D independently contribute to NAFLD risk in nonobese or lean individuals. MATERIALS AND METHODS This study analyzed 241208 asymptomatic health check-up examinees who had abdominal ultrasonography. NAFLD risk was evaluated based on obesity status and serum 25(OH)D levels. RESULTS The overall NAFLD prevalence was 25.5%. Among the 178630 nonobese and 126909 lean participants, the prevalence rates were 13.4% and 6.7%, respectively. The multivariable adjusted odds ratios (ORs) [95% confidence intervals (CI)] for the prevalence of NAFLD, comparing serum 25(OH)D levels of 10-19 and ≥20 ng/mL with <10 ng/mL, were 0.96 (0.93-0.99) and 0.80 (0.77-0.83), respectively. Among nonobese participants, the corresponding adjusted ORs (95% CI) were 0.94 (0.90-0.99) and 0.77 (0.73-0.81), respectively. Similar results were observed among lean participants, with those having a 25(OH)D level of ≥20 ng/mL demonstrating a significantly lower odds of NAFLD (adjusted OR, 0.76; 95% CI, 0.70-0.83). Moreover, these results were consistent even among nonobese and lean individuals who showed no signs of insulin resistance. CONCLUSION Insufficient 25(OH)D levels independently increased the risk of NAFLD, suggesting its role in the NAFLD pathogenesis, regardless of obesity or insulin resistance status. Considering the established relationship between vitamin D deficiency and nonobese/lean NAFLD, maintaining adequate 25(OH)D levels may aid in preventing the development of NAFLD, even among nonobese or lean individuals.
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Affiliation(s)
- Nam Hee Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hun Kang
- Department of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
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Hao Z, Lu Y, Hao Y, Luo Y, Wu K, Zhu C, Shi P, Zhu F, Lin Y, Zeng X. Fungal mycobiome dysbiosis in choledocholithiasis concurrent with cholangitis. J Gastroenterol 2025; 60:340-355. [PMID: 39604579 DOI: 10.1007/s00535-024-02183-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND The gut mycobiome might have an important influence on the pathogenesis of choledocholithiasis concurrent with cholangitis (CC). The aim of this study was to characterize the fungal mycobiome profiles, explore the correlation and equilibrium of gut interkingdom network among bacteria-fungi-metabolites triangle in CCs. METHODS In a retrospective case-control study, we recruited patients with CC (n = 25) and healthy controls (HCs) (n = 25) respectively to analyze the gut fungal dysbiosis. Metagenomic sequencing was employed to characterize the gut mycobiome profiles, and liquid chromatography/mass spectrometry (LC/MS) analysis was used to quantify the metabolites composition. RESULTS The Shannon index displayed a reduction in fungal α-diversity in CCs compared to HCs (p = 0.041), and the overall fungal composition differed significantly between two groups. The dominant 7 fungi species with the remarkable altered abundance were identified (LDA score > 3.0, p < 0.05), including CC-enriched Aspergillus_niger and CC-depleted fungi Saccharomyces_boulardii. In addition, the correlations between CC-related fungi and clinical variables in CCs were analyzed. Moreover, the increased abundance ratio of Basidiomycota-to-Ascomycota and a dense linkage of bacteria-fungi interkingdom network in CCs were demonstrated. Finally, we identified 30 markedly altered metabolites in CCs (VIP > 1.0 and p < 0.05), including low level of acetate and butyrate, and the deeper understanding on the complexity of bacteria-fungi-metabolites triangle involving bile inflammation was verified. CONCLUSION Our investigation demonstrated a distinct gut fungal dysbiosis in CCs and proposed that, beyond bacteria, the more attention should be paid to significantly potential influence of fungi and bacteria-fungi-metabolites triangle interkingdom interactions on pathogenesis of CC.
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Affiliation(s)
- Zhiyuan Hao
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yiting Lu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yarong Hao
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yuanyuan Luo
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Kaiming Wu
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Changpeng Zhu
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Peimei Shi
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Feng Zhu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China
| | - Yong Lin
- Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China.
| | - Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.
- Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China.
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Sitar ME, Donmez Cakil Y, Ipek BO, Altıner N, Aydin MS, Gunal H, Atamis AD, Karadeniz A. Experimental Vitamin D Deficiency in Rats: Clinical Chemistry, Histopathological, and Immunological Evaluation. Cureus 2024; 16:e67490. [PMID: 39310506 PMCID: PMC11416068 DOI: 10.7759/cureus.67490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2024] [Indexed: 09/25/2024] Open
Abstract
BACKGROUND Vitamin D deficiency is a significant global health concern. Experimental models are essential to elucidate the biochemical, histopathological, and immunological consequences of this deficiency. This study established a vitamin D deficiency rat model to mimic insufficient vitamin D intake and examine the resulting health impacts, particularly on liver, kidney, and immune functions. MATERIALS AND METHODS Sprague-Dawley male rats were randomly assigned to two groups. The control group received a standard rodent diet, while the experimental group was fed a modified diet with reduced vitamin D for three months. Analyses included serum vitamin D levels, clinical chemistry, renal and liver histopathology, and blood immunophenotyping and cytokine analysis for both the control (n=7) and experimental (n=7) groups. RESULTS Serum vitamin D 25-OH levels were threefold lower in the experimental group (p < 0.001), indicating the induction of vitamin D deficiency. No significant differences in weight gain were observed between the groups. All clinical chemistry parameters remained within reference ranges. However, the experimental group showed significant declines in triglycerides (TG, p=0.0441), alkaline phosphatase (ALP, p=0.0021), and alanine aminotransferase (ALT, p=0.0002). Histopathology revealed normal liver and kidney architecture in the control group, while the experimental group exhibited hepatic cord deterioration, severe vacuolization in the liver, and edema and dilatation in the renal cortex tubular epithelium. Immunophenotyping analysis of lymphocyte subsets and assessment of serum cytokines did not reveal any differences between the two groups. CONCLUSION A vitamin D deficiency model without complications such as obesity, parathyroid issues, or mortality was established in rats. This method could be applied in specific disease experimental models.
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Affiliation(s)
- Mustafa Erinc Sitar
- Department of Medical Biochemistry, Maltepe University Faculty of Medicine, Istanbul, TUR
| | - Yaprak Donmez Cakil
- Department of Histology and Embryology, Maltepe University Faculty of Medicine, Istanbul, TUR
| | - Belkiz Ongen Ipek
- Department of Medical Biochemistry, Maltepe University Faculty of Medicine, Istanbul, TUR
| | - Necdet Altıner
- Experimental Animals Research and Application Center, Maltepe University, Istanbul, TUR
| | - Mehmet Serif Aydin
- Regenerative and Restorative Medicine Research Center, Istanbul Medipol University, Istanbul, TUR
| | - Hakan Gunal
- Department of Medical Biochemistry, Maltepe University Faculty of Medicine, Istanbul, TUR
| | - Ali Diyar Atamis
- Department of Medical Biochemistry, Maltepe University Faculty of Medicine, Istanbul, TUR
| | - Aslı Karadeniz
- Department of Infectious Diseases, Maltepe University Faculty of Medicine, Istanbul, TUR
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Ullah A, Singla RK, Batool Z, Cao D, Shen B. Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases). Rev Endocr Metab Disord 2024; 25:783-803. [PMID: 38709387 DOI: 10.1007/s11154-024-09884-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/01/2024] [Indexed: 05/07/2024]
Abstract
Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.
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Affiliation(s)
- Amin Ullah
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Rajeev K Singla
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- School of Pharmaceutical Sciences, Lovely Professional University, 144411, Phagwara, Punjab, India
| | - Zahra Batool
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Cao
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Bairong Shen
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
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Aggeletopoulou I, Tsounis EP, Triantos C. Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights. Int J Mol Sci 2024; 25:4901. [PMID: 38732118 PMCID: PMC11084591 DOI: 10.3390/ijms25094901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.
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Affiliation(s)
| | | | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
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Tyczyńska M, Hunek G, Szczasny M, Brachet A, Januszewski J, Forma A, Portincasa P, Flieger J, Baj J. Supplementation of Micro- and Macronutrients-A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2024; 25:4916. [PMID: 38732128 PMCID: PMC11085010 DOI: 10.3390/ijms25094916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/28/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro- and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter.
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Affiliation(s)
- Magdalena Tyczyńska
- Department of Correct, Clinical and Imaging Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland;
| | - Gabriela Hunek
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Martyna Szczasny
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| | - Adam Brachet
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Jacek Januszewski
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Jolanta Flieger
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland;
| | - Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
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Lee SB, Jin MH, Yoon JH. The contribution of vitamin D insufficiency to the onset of steatotic liver disease among individuals with metabolic dysfunction. Sci Rep 2024; 14:6714. [PMID: 38509247 PMCID: PMC10954610 DOI: 10.1038/s41598-024-57380-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 03/18/2024] [Indexed: 03/22/2024] Open
Abstract
The interplay between fatty liver disease (FLD) and metabolic dysfunction has given rise to the concept of metabolic associated fatty liver disease (MAFLD). With vitamin D insufficiency frequently co-occurring with FLD and linked to metabolic abnormalities, this study investigates the potential role of vitamin D in the development of MAFLD. In this cross-sectional analysis, 22,476 participants with baseline metabolic dysfunction and known serum 25-OH-vitamin D3 levels were examined. The fatty liver index (FLI) was utilized to predict FLD, dividing subjects into MAFLD and non-MAFLD groups. Further stratification by vitamin D levels (sufficient vs. insufficient) and gender provided a detailed assessment through binary logistic regression to determine the association of vitamin D status with MAFLD incidence. Vitamin D insufficiency correlated with a higher MAFLD incidence in metabolically impaired individuals. Post-adjustment, the correlation was stronger (men: aOR = 1.32, 95% CI = 1.22-1.43, P < 0.001; women: aOR = 1.53, 95% CI = 1.18-1.98, P = 0.001). Lower serum 25-OH-vitamin D3 levels were found in MAFLD patients across genders (men: P = 0.003; women: P = 0.014), with a higher prevalence of insufficiency in MAFLD cases (men: P = 0.007; women: P = 0.003). The vitamin D-MAFLD link was stable across subgroups and using varying FLI criteria. Our findings indicate a clear association between vitamin D insufficiency and increased MAFLD incidence, underscoring the potential of vitamin D as an anti-lipogenic and anti-fibrotic agent.
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Affiliation(s)
- Su-Bin Lee
- Department of Pharmacy, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Mi Hyeon Jin
- Department of Research Support, Samsung Changwon Hospital, School of Medicine, Sungkyunkwan University, Changwon, Korea
| | - Jeong-Hyun Yoon
- College of Pharmacy and Research Institute for Drug Development, Pusan National University, 2, Busandaehak-ro, 63 Beon-gil, Geumjeong-gu, Busan, 46241, South Korea.
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Liu Y, Qin X, Chen T, Chen M, Wu L, He B. Exploring the interactions between metabolic dysfunction-associated fatty liver disease and micronutrients: from molecular mechanisms to clinical applications. Front Nutr 2024; 11:1344924. [PMID: 38549744 PMCID: PMC10973017 DOI: 10.3389/fnut.2024.1344924] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 03/05/2024] [Indexed: 01/06/2025] Open
Abstract
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition's progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD's pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.
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Affiliation(s)
- Yuan Liu
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Xiang Qin
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Tianzhu Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Mengyao Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Liyan Wu
- Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Beihui He
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
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Li X, Pan C, Ma W, Yang T, Wang C, Han W, Zhang W, Li H, Li Z, Zhao T, Guo XF, Li D. Effects of dietary supplementation of fish oil plus vitamin D 3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial. Food Funct 2024; 15:2616-2627. [PMID: 38356413 DOI: 10.1039/d3fo02319b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.
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Affiliation(s)
- Xueqi Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
- Binzhou Center for Disease Control and Prevention, Binzhou, China
| | - Chi Pan
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Wenjun Ma
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Ting Yang
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Chong Wang
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Weiwei Han
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Wei Zhang
- Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Li
- Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhongxia Li
- Byhealth Institute of Nutrition & Health, Guangzhou, China
| | - Ting Zhao
- Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao-Fei Guo
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Duo Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
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11
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Qian QH, Song YP, Zhang Y, Xue H, Zhang WW, Han Y, Wāng Y, Xu DX. Gestational α-ketoglutarate supplementation ameliorates arsenic-induced hepatic lipid deposition via epigenetic reprogramming of β-oxidation process in female offspring. ENVIRONMENT INTERNATIONAL 2024; 185:108488. [PMID: 38359550 DOI: 10.1016/j.envint.2024.108488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/11/2024] [Accepted: 02/05/2024] [Indexed: 02/17/2024]
Abstract
Inorganic trivalent arsenic (iAsⅢ) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsⅢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsⅢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsⅢ at an environmentally relevant concentration disturbs lipid metabolism and reduces levels of alpha-ketoglutaric acid (α-KG), an important mitochondrial metabolite during the citric acid cycle, in fetal livers. Further, gestational supplementation of α-KG alleviated hepatic lipid deposition caused by early-life exposure to iAsⅢ. This beneficial effect was particularly pronounced in female offspring. α-KG partially restored the β-oxidation process in hepatic tissues by hydroxymethylation modifications of carnitine palmitoyltransferase 1a (Cpt1a) gene during fetal development. Insufficient β-oxidation capacities probably play a crucial role in hepatic lipid deposition in adulthood following in utero arsenite exposure, which can be efficiently counterbalanced by replenishing α-KG. These results suggest that gestational administration of α-KG can ameliorate hepatic lipid deposition caused by iAsⅢ in female adult offspring partially through epigenetic reprogramming of the β-oxidation pathway. Furthermore, α-KG shows potential as an interventive target to mitigate the harmful effects of arsenic-induced hepatic developmental toxicity.
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Affiliation(s)
- Qing-Hua Qian
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China
| | - Ya-Ping Song
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China
| | - Yu Zhang
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China
| | - Hao Xue
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China
| | - Wei-Wei Zhang
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China
| | - Yapeng Han
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China
| | - Yán Wāng
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China.
| | - De-Xiang Xu
- Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, School of Public Health, Anhui Medical University, Hefei 230032, China.
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12
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Zhou C, Zhang Y, Ye Z, He P, Zhang Y, Gan X, Yang S, Liu M, Wu Q, Qin X. Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease. Nutrition 2024; 119:112320. [PMID: 38185094 DOI: 10.1016/j.nut.2023.112320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/27/2023] [Accepted: 11/28/2023] [Indexed: 01/09/2024]
Abstract
OBJECTIVES The prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association. METHODS The study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death. RESULTS During a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84-0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; Pinteraction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (Pinteraction = 0.216). CONCLUSIONS Lower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.
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Affiliation(s)
- Chun Zhou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Yanjun Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Ziliang Ye
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Panpan He
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Yuanyuan Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Xiaoqin Gan
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Sisi Yang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Mengyi Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Qimeng Wu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Xianhui Qin
- Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China.
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Singh A, Buckholz A, Kumar S, Newberry C. Implications of Protein and Sarcopenia in the Prognosis, Treatment, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Nutrients 2024; 16:658. [PMID: 38474786 DOI: 10.3390/nu16050658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 02/22/2024] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open
Abstract
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a common cause of chronic liver disease globally, with prevalence rapidly increasing in parallel with rising rates of obesity and metabolic syndrome. MASLD is defined by the presence of excess fat in the liver, which may induce inflammatory changes and subsequent fibrosis in high-risk patients. Though MASLD occurs frequently, there is still no approved pharmacological treatment, and the mainstay of therapy remains lifestyle modification via dietary changes, enhancement of physical activity, and management of metabolic comorbidities. Most nutrition research and clinical guidance in this disease centers on the reduction in fructose and saturated fat in the diet, although the emerging literature suggests that protein supplementation is important and implicates muscle mass and sarcopenia in disease-related outcomes. This review will assess the current data on these topics, with the goal of defining best practices and identifying research gaps in care.
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Affiliation(s)
- Avneet Singh
- Department of Medicine, Cooper University Hospital, Camden, NJ 08103, USA
| | - Adam Buckholz
- Division of Gastroenterology, Weill Cornell Medical Center, New York, NY 10065, USA
| | - Sonal Kumar
- Division of Gastroenterology, Weill Cornell Medical Center, New York, NY 10065, USA
| | - Carolyn Newberry
- Division of Gastroenterology, Weill Cornell Medical Center, New York, NY 10065, USA
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Zhou Y, Chen Y, Chen F, Li G, Zhou L. Association of serum 25-hydroxyvitamin D concentrations with all-cause and cardiovascular mortality among US adults with prehypertension: a prospective cohort study. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:24. [PMID: 38321509 PMCID: PMC10848370 DOI: 10.1186/s41043-024-00515-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 01/28/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND Prehypertension affects 25-50% of adults worldwide and no prior study has examined the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality risk in individuals with prehypertension. This study aims to investigate the association of serum 25(OH)D concentrations with all-cause and CVD mortality among prehypertensive adults by utilizing data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2014 and linked 2019 mortality file. METHODS We included 4345 prehypertensive adults who participated in the NHANES between 2007 and 2014 and were followed up until 31 December 2019. Weighted Cox proportional hazards models were used with adjustments for multiple covariates to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risks of dying from any cause and CVD. RESULTS During a median follow-up of 8.8 years, 335 deaths from any causes were documented, of which 88 participants died from CVD. Compared with participants with sufficient 25(OH)D (≥ 75 nmol/L), the multivariate-adjusted HRs and 95% CIs for participants with severe deficiency (< 25 nmol/L), moderate deficiency (25-49.9 nmol/L), and insufficient concentrations (50-74.9 nmol/L) of serum 25(OH)D for all-cause death were 2.83 (1.46-5.52), 1.17 (0.74-1.86), and 1.36 (0.93-1.98), respectively. Similarly, the multivariable-adjusted HRs and 95%CIs for CVD death were 4.14 (1.10-15.51), 1.23 (0.46-3.28), and 1.73 (0.96-3.14), respectively. We found that there was a 9% reduction in the risk of death from all causes and a 14% reduction in the risk of death from CVD for every 10 nmol/L increase in serum 25(OH)D concentrations. CONCLUSION Severe serum 25(OH)D deficiency among prehypertensive adults was associated with increased risk of mortality from all causes as well as from CVD. Our work suggests that supplementing with vitamin D may prevent premature death in severely deficient individuals with prehypertension.
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Affiliation(s)
- Yongmei Zhou
- Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yu Chen
- Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Fuli Chen
- Institute of Cardiovascular Diseases and Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Gang Li
- Institute of Cardiovascular Diseases and Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| | - Long Zhou
- Institute of Cardiovascular Diseases and Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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Wi D, Park CY. 1,25-dihydroxyvitamin D 3 affects thapsigargin-induced endoplasmic reticulum stress in 3T3-L1 adipocytes. Nutr Res Pract 2024; 18:1-18. [PMID: 38352211 PMCID: PMC10861344 DOI: 10.4162/nrp.2024.18.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/01/2023] [Accepted: 12/06/2023] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND/OBJECTIVES Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) alleviates ER stress in adipocytes. MATERIALS/METHODS 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS Treatment with 1,25(OH)2D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2D3 treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)2D3 administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2D3 inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS Our data suggest that 1,25(OH)2D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.
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Affiliation(s)
- Dain Wi
- Department of Food & Nutrition, College of Health Science, The University of Suwon, Hwaseong 18323, Korea
| | - Chan Yoon Park
- Department of Food & Nutrition, College of Health Science, The University of Suwon, Hwaseong 18323, Korea
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Kim GH, Jeong HJ, Lee YJ, Park HY, Koo SK, Lim JH. Vitamin D ameliorates age-induced nonalcoholic fatty liver disease by increasing the mitochondrial contact site and cristae organizing system (MICOS) 60 level. Exp Mol Med 2024; 56:142-155. [PMID: 38172593 PMCID: PMC10834941 DOI: 10.1038/s12276-023-01125-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 08/27/2023] [Accepted: 10/04/2023] [Indexed: 01/05/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Despite intensive research, considerable information on NAFLD development remains elusive. In this study, we examined the effects of vitamin D on age-induced NAFLD, especially in connection with mitochondrial abnormalities. We observed the prevention of NAFLD in 22-month-old C57BL/6 mice fed a vitamin D3-supplemented (20,000 IU/kg) diet compared with mice fed a control (1000 IU/kg) diet. We evaluated whether vitamin D3 supplementation enhanced mitochondrial functions. We found that the level of mitochondrial contact site and cristae organizing system (MICOS) 60 (Mic60) level was reduced in aged mice, and this reduction was specifically restored by vitamin D3. In addition, depletion of Immt, the human gene encoding the Mic60 protein, induced changes in gene expression patterns that led to fat accumulation in both HepG2 and primary hepatocytes, and these alterations were effectively prevented by vitamin D3. In addition, silencing of the vitamin D receptor (VDR) decreased the Mic60 levels, which were recovered by vitamin D treatment. To assess whether VDR directly regulates Mic60 levels, we performed chromatin immunoprecipitation and reporter gene analysis. We discovered that VDR directly binds to the Immt 5' promoter region spanning positions -3157 to -2323 and thereby upregulates Mic60. Our study provides the first demonstration that a reduction in Mic60 levels due to aging may be one of the mechanisms underlying the development of aging-associated NAFLD. In addition, vitamin D3 could positively regulate Mic60 expression, and this may be one of the important mechanisms by which vitamin D could ameliorate age-induced NAFLD.
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Affiliation(s)
- Gyu Hee Kim
- Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea
| | - Hyeon-Ju Jeong
- Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea
| | - Yoo Jeong Lee
- Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea
| | - Hyeon Young Park
- Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea
| | - Soo Kyung Koo
- Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea
| | - Joo Hyun Lim
- Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea.
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LIANTO D, DJABIR YY, MUSTAMU BO, ARSYAD A. Vitamin D was Superior to Omega-3 as a Simvastatin Adjuvant in Improving Blood Lipids and Atherogenic Index in Type-I Dyslipidemic Rats. Turk J Pharm Sci 2024; 20:390-396. [PMID: 38256280 PMCID: PMC10803921 DOI: 10.4274/tjps.galenos.2023.56958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 02/01/2023] [Indexed: 02/11/2023]
Abstract
Objectives Adjuvant therapy is often used to optimize the antihyperlipidemic effect of simvastatin. Omega-3 and vitamin D supplementation are recommended as adjuvant therapies to low-intensity statins. This study aimed to compare the effects of vitamin D and omega-3 as adjuvant therapy to simvastatin to improve the lipid profiles and atherogenic index of plasma (AIP) in type-I dyslipidemic rats. Materials and Methods Thirty-six male rats were randomized and divided into six groups: healthy control, dyslipidemic rats with no treatment, and dyslipidemic rats treated with either low-dose simvastatin only or omega-3 or vitamin D at low and high doses. Dyslipidemia was induced with high-fat diets for four weeks, followed by treatment for the next two weeks. Blood samples were withdrawn before and after simvastatin treatment. In addition, aspartate transaminase (AST) and alanine transaminase (ALT) levels were analyzed to assess liver function. Results Administration of a high-fat diet-induced type 1 dyslipidemia and increased ALT levels (p < 0.05). Treatment with low-dose simvastatin did not significantly improve triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc) or non-HDLc levels. When combined with a high-dose vitamin D, simvastatin significantly reduced TG and increased HDLc levels (p < 0.05), thereby improving AIP levels. This improvement was not observed in rats treated with omega-3 or vitamin D at a lower dose. Conclusion We concluded that high-dose vitamin D as an adjuvant to simvastatin therapy was superior to omega-3 in improving TG, HDL, and AIP levels. High-dose vitamin D also improved ALT levels in type-I dyslipidemic rats. This result may be translated in clinics to reduce the risk of coronary syndrome in patients with type-I dyslipidemia.
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Affiliation(s)
- Devy LIANTO
- Hasanuddin University, Faculty of Pharmacy, Graduate Program, Makassar, Indonesia
| | - Yulia Yusrini DJABIR
- Hasanuddin University, Faculty of Pharmacy, Laboratory of Clinical Pharmacy, Makassar, Indonesia
| | | | - Aryadi ARSYAD
- Hasanuddin University, Faculty of Medicine, Department of Physiology, Makassar, Indonesia
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Abdelrahman BA, Hammam OA, El-Khatib AS, Attia YM. The role of vitamin D3 in modulating the interplay between NLRP3 inflammasome and autophagy in NASH. Biochem Biophys Res Commun 2023; 688:149122. [PMID: 37951152 DOI: 10.1016/j.bbrc.2023.149122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/26/2023] [Accepted: 10/15/2023] [Indexed: 11/13/2023]
Abstract
Damage-associated molecular patterns released upon hepatocyte injury ensuing non-alcoholic steatohepatitis (NASH) can stimulate innate immunity by activating NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, thereby triggering pro-inflammatory cascades in the liver. Aberrant NLRP3 activation allied to compromised autophagic clearance of its components contributes to the progression of multiple inflammatory diseases. Such intricate interplay, however, was not fully deciphered in NASH. Prior studies have illuminated the ability of vitamin D3 to temper inflammasome activation in several contexts, prompting us to probe the impact of vitamin D3, particularly its active form, calcitriol (CAL), on NLRP3 overactivation in a high-fat diet (HFD)-based NASH model and its potential dependence on autophagy. Hydroxychloroquine (HCQ), an autophagy inhibitor, was co-administered with CAL to examine the likely modulation of the NLRP3/autophagy crosstalk. Our results showed that treatment with CAL countervailed the histopathological derangement reported in the livers of HFD-fed mice that paralleled a restoration of vitamin D receptor gene expression and reduction in sterol regulatory element binding protein 1c levels. Moreover, p62 was curtailed with CAL treatment indicating autophagy induction. CAL also prompted a reduction in NLRP3, caspase-1, gasdermin D, and IL-18 protein levels along with the apoptosis-associated speck-like protein (ASC) gene expression. Treatment with CAL also reduced IL-1β and caspase-3 immunoreactivities compared to control. Intriguingly, CAL modulatory effects on inflammasome activation were curbed in the group that received HCQ, suggesting a potential autophagy dependency. Accordingly, the current study suggests that CAL was capable of ameliorating NASH via inhibiting NLRP3 inflammasome activation in an autophagy-dependent manner.
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Affiliation(s)
- Basma A Abdelrahman
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
| | - Olfat A Hammam
- Pathology Department, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Aiman S El-Khatib
- Pharmacology Department, Faculty of Pharmacy, Cairo University, Egypt.
| | - Yasmeen M Attia
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
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Abdelrahman BA, El-Khatib AS, Attia YM. Insights into the role of vitamin D in targeting the culprits of non-alcoholic fatty liver disease. Life Sci 2023; 332:122124. [PMID: 37742738 DOI: 10.1016/j.lfs.2023.122124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/12/2023] [Accepted: 09/21/2023] [Indexed: 09/26/2023]
Abstract
Vitamin D (VD) is a secosteroid hormone that is renowned for its crucial role in phospho-calcium homeostasis upon binding to the nuclear vitamin D receptor (VDR). Over and above, the pleiotropic immunomodulatory, anti-inflammatory, and metabolic roles VD plays in different disease settings started to surface in the past few decades. On the other hand, a growing body of evidence suggests a correlation between non-alcoholic fatty liver disease (NAFLD) and its progressive inflammatory form non-alcoholic steatohepatitis (NASH) with vitamin D deficiency (VDD) owing to the former's ingrained link with obesity and metabolic syndrome. Accordingly, a better understanding of the contribution of disrupted VDR signalling to NAFLD incidence and progression would provide further insights into its diagnosis, treatment modalities, and prognosis. This is especially significant as, hitherto, no drug for NAFLD has been approved. This review, therefore, sought to set forth the likely contribution of VDR signalling in NAFLD and how it might influence its multiple drivers.
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Affiliation(s)
- Basma A Abdelrahman
- Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
| | - Aiman S El-Khatib
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Yasmeen M Attia
- Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
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Humbert A, Lefebvre R, Nawrot M, Caussy C, Rieusset J. Calcium signalling in hepatic metabolism: Health and diseases. Cell Calcium 2023; 114:102780. [PMID: 37506596 DOI: 10.1016/j.ceca.2023.102780] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023]
Abstract
The flexibility between the wide array of hepatic functions relies on calcium (Ca2+) signalling. Indeed, Ca2+ is implicated in the control of many intracellular functions as well as intercellular communication. Thus, hepatocytes adapt their Ca2+ signalling depending on their nutritional and hormonal environment, leading to opposite cellular functions, such as glucose storage or synthesis. Interestingly, hepatic metabolic diseases, such as obesity, type 2 diabetes and non-alcoholic fatty liver diseases, are associated with impaired Ca2+ signalling. Here, we present the hepatocytes' toolkit for Ca2+ signalling, complete with regulation systems and signalling pathways activated by nutrients and hormones. We further discuss the current knowledge on the molecular mechanisms leading to alterations of Ca2+ signalling in hepatic metabolic diseases, and review the literature on the clinical impact of Ca2+-targeting therapeutics.
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Affiliation(s)
- Alexandre Humbert
- Laboratoire CarMeN, INSERM U-1060, INRAE U-1397, Université Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France
| | - Rémy Lefebvre
- Laboratoire CarMeN, INSERM U-1060, INRAE U-1397, Université Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France
| | - Margaux Nawrot
- Laboratoire CarMeN, INSERM U-1060, INRAE U-1397, Université Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France
| | - Cyrielle Caussy
- Laboratoire CarMeN, INSERM U-1060, INRAE U-1397, Université Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France; Département Endocrinologie, Diabète et Nutrition, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France
| | - Jennifer Rieusset
- Laboratoire CarMeN, INSERM U-1060, INRAE U-1397, Université Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France.
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Liu J, Song Y, Wang Y, Hong H. Vitamin D/vitamin D receptor pathway in non-alcoholic fatty liver disease. Expert Opin Ther Targets 2023; 27:1145-1157. [PMID: 37861098 DOI: 10.1080/14728222.2023.2274099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 10/18/2023] [Indexed: 10/21/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, but underlying mechanisms are not fully understood. In recent years, a growing body of evidence has emphasized the therapeutic role of vitamin D in NAFLD, but the specific mechanism remains to be investigated. AREAS COVERED This review summarized the roles of vitamin D/VDR (vitamin D receptor) pathway in different types of liver cells (such as hepatocytes, hepatic stellate cells, liver macrophages, T lymphocytes, and other hepatic immune cells) in case of NAFLD. Meanwhile, the effects of pathways in the gut-liver axis, adipose tissue-liver axis, and skeletal muscle-liver axis on the development of NAFLD were further reviewed. Relevant literature was searched on PubMed for the writing of this review. EXPERT OPINION The precise regulation of regional vitamin D/VDR signaling pathway based on cell-specific or tissue-specific function will help clarify the potential mechanism of vitamin D in NAFLD, which may provide new therapeutic targets to improve the safety and efficacy of vitamin D based drugs.
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Affiliation(s)
- Jingqi Liu
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Xiamen Institute of Geriatric Rehabilitation, Department of Geriatrics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Yang Song
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Ye Wang
- Xiamen Institute of Geriatric Rehabilitation, Department of Geriatrics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Huashan Hong
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Zhang Z, Burrows K, Fuller H, Speliotes EK, Abeysekera KWM, Thorne JL, Lewis SJ, Zulyniak MA, Moore JB. Non-Alcoholic Fatty Liver Disease and Vitamin D in the UK Biobank: A Two-Sample Bidirectional Mendelian Randomisation Study. Nutrients 2023; 15:1442. [PMID: 36986172 PMCID: PMC10058870 DOI: 10.3390/nu15061442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/06/2023] [Accepted: 03/13/2023] [Indexed: 03/19/2023] Open
Abstract
Evidence for a role for vitamin D in non-alcoholic fatty liver disease (NAFLD) pathogenesis is conflicting. As Mendelian randomisation (MR) avoids many limitations of conventional observational studies, this two-sample bidirectional MR analysis was conducted to determine the following: (i) whether genetically predicted 25-hydroxyvitamin D [25(OH)D] levels are a risk factor for NAFLD, and (ii) whether genetic risk for NAFLD influences 25(OH)D levels. Single-nucleotide polymorphisms (SNPs) associated with serum 25(OH)D levels were obtained from the European ancestry-derived SUNLIGHT consortium. SNPs associated with NAFLD or NASH (p-value < 1 × 10-5) were extracted from previous studies and supplemented by genome-wide association studies (GWASs) performed in the UK Biobank. These GWASs were done both without (primary analysis) and with (sensitivity analysis) the population-level exclusion of other liver diseases (e.g., alcoholic liver diseases, toxic liver diseases, viral hepatitis, etc.). Subsequently, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic, MR-Egger regression intercept, MR pleiotropy residual sum and outlier (MR-PRESSO) analyses were used to assess pleiotropy. No causal association of genetically predicted serum 25(OH)D (per standard deviation increase) with risk of NAFLD was identified in either the primary analysis: n = 2757 cases, n = 460,161 controls, odds ratio (95% confidence interval): 0.95 (0.76, -1.18), p = 0.614; or the sensitivity analysis. Reciprocally, no causal association was identified between the genetic risk of NAFLD and serum 25(OH)D levels, OR = 1.00 (0.99, 1.02, p = 0.665). In conclusion, this MR analysis found no evidence of an association between serum 25(OH)D levels and NAFLD in a large European cohort.
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Affiliation(s)
- Zixuan Zhang
- School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK
- Department of Medicine, National University of Singapore, Singapore 117549, Singapore
| | - Kimberley Burrows
- Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
| | - Harriett Fuller
- School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK
- Public Health Science Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
| | - Elizabeth K. Speliotes
- Divisions of Gastroenterology, Computational Medicine and Bioinformatics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Kushala W. M. Abeysekera
- Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
| | - James L. Thorne
- School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK
| | - Sarah J. Lewis
- Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
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Rizzo M, Colletti A, Penson PE, Katsiki N, Mikhailidis DP, Toth PP, Gouni-Berthold I, Mancini J, Marais D, Moriarty P, Ruscica M, Sahebkar A, Vinereanu D, Cicero AFG, Banach M, Al-Khnifsawi M, Alnouri F, Amar F, Atanasov AG, Bajraktari G, Banach M, Gouni-Berthold I, Bhaskar S, Bielecka-Dąbrowa A, Bjelakovic B, Bruckert E, Bytyçi I, Cafferata A, Ceska R, Cicero AF, Chlebus K, Collet X, Daccord M, Descamps O, Djuric D, Durst R, Ezhov MV, Fras Z, Gaita D, Gouni-Berthold I, Hernandez AV, Jones SR, Jozwiak J, Kakauridze N, Kallel A, Katsiki N, Khera A, Kostner K, Kubilius R, Latkovskis G, John Mancini G, David Marais A, Martin SS, Martinez JA, Mazidi M, Mikhailidis DP, Mirrakhimov E, Miserez AR, Mitchenko O, Mitkovskaya NP, Moriarty PM, Mohammad Nabavi S, Nair D, Panagiotakos DB, Paragh G, Pella D, Penson PE, Petrulioniene Z, Pirro M, Postadzhiyan A, Puri R, Reda A, Reiner Ž, Radenkovic D, Rakowski M, Riadh J, Richter D, Rizzo M, Ruscica M, Sahebkar A, Serban MC, Shehab AM, Shek AB, Sirtori CR, Stefanutti C, Tomasik T, Toth PP, Viigimaa M, Valdivielso P, Vinereanu D, Vohnout B, von Haehling S, Vrablik M, Wong ND, Yeh HI, Zhisheng J, Zirlik A. Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2023; 189:106679. [PMID: 36764041 DOI: 10.1016/j.phrs.2023.106679] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/11/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
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Affiliation(s)
- Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, Turin, Italy
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, Medical School, University College London (UCL), London, UK
| | - Peter P Toth
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA
| | - Ioanna Gouni-Berthold
- Department of Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany
| | - John Mancini
- Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Marais
- Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
| | - Patrick Moriarty
- Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Dragos Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Arrigo Francesco Giuseppe Cicero
- Hypertension and Cardiovascular disease risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; IRCCS Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
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Yuan S, Larsson SC. Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2023; 21:398-405.e4. [PMID: 35101633 DOI: 10.1016/j.cgh.2022.01.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/12/2022] [Accepted: 01/17/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Affiliation(s)
- Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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Joo SK, Kim W. Interaction between sarcopenia and nonalcoholic fatty liver disease. Clin Mol Hepatol 2023; 29:S68-S78. [PMID: 36472051 PMCID: PMC10029947 DOI: 10.3350/cmh.2022.0358] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Sarcopenia and nonalcoholic fatty liver disease (NAFLD) are common health problems related to aging. Despite the differences in their diagnostic methods, several cross-sectional and longitudinal studies have revealed the close link between sarcopenia and NAFLD. Sarcopenia and NAFLD are linked by several shared pathogenetic mechanisms, including insulin resistance, hormonal imbalance, systemic inflammation, myostatin and adiponectin dysregulation, nutritional deficiencies, and physical inactivity, thus implicating a bidirectional relationship between sarcopenia and NAFLD. However, there is not sufficient data to support a direct causal relationship between sarcopenia and NAFLD. Moreover, it is currently difficult to conclude whether sarcopenia is a risk factor for nonalcoholic steatohepatitis (NASH) or is a consequence of NASH. Therefore, this review intends to touch on the shared common mechanisms and the bidirectional relationship between sarcopenia and NAFLD.
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Affiliation(s)
- Sae Kyung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Efficacy of Submicron Dispersible Free Phytosterols on Non-Alcoholic Fatty Liver Disease: A Pilot Study. J Clin Med 2023; 12:jcm12030979. [PMID: 36769628 PMCID: PMC9918217 DOI: 10.3390/jcm12030979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND No pharmacological treatment is yet approved for non-alcoholic fatty liver disease (NAFLD). Plant sterols have shown healthy properties beyond lowering LDL-cholesterol, including lowering triglycerides and lipoprotein plasma levels. Despite pre-clinical data suggesting their involvement in liver fat control, no clinical study has yet been successful. AIMS Testing a sub-micron, free, phytosterol dispersion efficacy on NAFLD. METHODS A prospective, uncontrolled pilot study was carried out on 26 patients with ≥17.4% liver steatosis quantified by magnetic resonance imaging. Subjects consumed daily a sub-micron dispersion providing 2 g of phytosterols. Liver fat, plasma lipids, lipoproteins, liver enzymes, glycemia, insulinemia, phytosterols, liposoluble vitamins and C-reactive protein were assessed at baseline and after one year of treatment. RESULTS Liver steatosis relative change was -19%, and 27% of patients reduced liver fat by more than 30%. Statistically and clinically significant improvements in plasma triglycerides, HDL-C, VLDL and HDL particle number and C-reactive protein were obtained, despite the rise of aspartate aminotransferase, glycemia and insulinemia. Though phytosterol plasma levels were raised by >30%, no adverse effects were presented, and even vitamin D increased by 23%. CONCLUSIONS Our results are the first evidence in humans of the efficacy of submicron dispersible phytosterols for the treatment of liver steatosis, dyslipidemia and inflammatory status in NAFLD.
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KEÇELİ BAŞARAN M, GÜRKAN O. Analysis of clinical findings and serum micronutrients in pediatric patients with nonalcoholic fatty liver disease. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2023. [DOI: 10.32322/jhsm.1190206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Aim: Serum micronutrient levels play an important role in liver metabolism. This study examines risk factors and diagnostic methods for patients on follow-up due to nonalcoholic fatty liver disease (NAFLD). NAFLD and the control groups were compared for clinical findings, serum ferritin, B12, and vitamin D levels, and their relationship with NAFLD was examined.
Material and Method: Included in the study were 60 NAFLD patients and 66 other children that formed the control group. The two groups were compared in serum lipid profile, aminotransferase, insulin, glucose, and HOMA-IR. Ultrasonography (USG) and Shear wave elastography (SWE) were performed on all patients. Both groups were then analyzed in terms of serum ferritin, B12, and vitamin D levels.
Results: NAFLD and control groups were compared in terms of USG and SWE results. 35% (n=21)of the patients in the NAFLD group had grade 1, 55% (n=33) had grade 2 and 10% (n=6) had grade 3 adiposity. HOMA-IR and insulin levels were higher in the NAFLD group (p=0.02; p=0.001). While the serum ferritin level of the patients in the NAFLD group was higher than the control group (p=0.001); the B12 level was lower (p=0.006). In terms of vitamin D, there was no difference (p=0.368).
Conclusion: It is essential to identify risk factors in children on follow-up due to NAFLD. USG and liver function tests remain the first option in the diagnosis and screening of NAFLD in children. Serum ferritin, B12, and vitamin D levels of children on follow-up due to NAFLD should be analyzed in consideration of liver fattening.
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Affiliation(s)
- Meryem KEÇELİ BAŞARAN
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL BAŞAKŞEHİR ÇAM VE SAKURA ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, ÇOCUK SAĞLIĞI VE HASTALIKLARI ANABİLİM DALI
| | - Okan GÜRKAN
- İSTANBUL GAZİOSMANPAŞA TAKSİM EĞİTİM VE ARAŞTIRMA HASTANESİ, RADYOLOJİ
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Manoppo JIC, Pateda V, Prayogo C, Langi FLFG, Nurkolis F, Tsopmo A. Relationships of 25-hydroxyvitamin D levels and non-alcoholic fatty liver disease in obese children: A possible strategy to promote early screening of NAFLD. Front Nutr 2022; 9:1025396. [PMID: 36407527 PMCID: PMC9667029 DOI: 10.3389/fnut.2022.1025396] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/11/2022] [Indexed: 09/29/2023] Open
Affiliation(s)
- Jeanette Irene Christiene Manoppo
- Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Department of Pediatrics, Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | - Vivekenanda Pateda
- Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Department of Pediatrics, Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | - Cindy Prayogo
- Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Department of Pediatrics, Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | | | - Fahrul Nurkolis
- Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga Yogyakarta), Yogyakarta, Indonesia
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Kolieb E, Maher SA, Shalaby MN, Alsuhaibani AM, Alharthi A, Hassan WA, El-Sayed K. Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:13740. [PMID: 36360622 PMCID: PMC9656563 DOI: 10.3390/ijerph192113740] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 11/05/2022]
Abstract
The prevalence of obesity has risen in the last decades, and it has caused massive health burdens on people's health, especially metabolic and cardiovascular issues. The risk of vitamin D insufficiency is increased by obesity, because adipose tissue alters both the requirements for and bioavailability of vitamin D. Exercise training is acknowledged as having a significant and long-term influence on body weight control; the favorable impact of exercise on obesity and obesity-related co-morbidities has been demonstrated via various mechanisms. The current work illustrated the effects of vitamin D supplementation and exercise on obesity induced by a high-fat diet (HFD) and hepatic steatosis in rats and explored how fatty acid transport protein-4 (FATP4) and Toll-like receptor-4 antibodies (TLR4) might be contributing factors to obesity and related hepatic steatosis. Thirty male albino rats were divided into five groups: group 1 was fed a normal-fat diet, group 2 was fed an HFD, group 3 was fed an HFD and given vitamin D supplementation, group 4 was fed an HFD and kept on exercise, and group 5 was fed an HFD, given vitamin D, and kept on exercise. The serum lipid profile adipokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were analyzed, and the pathological changes in adipose and liver tissues were examined. In addition, the messenger-ribonucleic acid (mRNA) expression of FATP4 and immunohistochemical expression of TLR4 in adipose and liver tissues were evaluated. Vitamin D supplementation and exercise improved HFD-induced weight gain and attenuated hepatic steatosis, along with improving the serum lipid profile, degree of inflammation, and serum adipokine levels. The expression of FATP4 and TLR4 in both adipose tissue and the liver was downregulated; it was noteworthy that the group that received vitamin D and was kept on exercise showed also improvement in the histopathological picture of this group. According to the findings of this research, the protective effect of vitamin D and exercise against obesity and HFD-induced hepatic steatosis is associated with the downregulation of FATP4 and TLR4, as well as a reduction in inflammation.
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Affiliation(s)
- Eman Kolieb
- Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Shymaa Ahmed Maher
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
- Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Mohammed Nader Shalaby
- Biological Sciences and Sports Health Department, Faculty of Physical Education, Suez Canal University, Ismailia 41522, Egypt
| | - Amnah Mohammed Alsuhaibani
- Department of Physical Sport Science, College of Education, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Afaf Alharthi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Wael A. Hassan
- Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
- Department of Basic Sciences, College of Medicine, Sulaiman Alrajhi University, Al Bukayriyah 52726, Saudi Arabia
| | - Karima El-Sayed
- Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
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Antitoxic Effects of Curcumin against Obesity-Induced Multi-Organs' Biochemical and Histopathological Abnormalities in an Animal Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9707278. [PMID: 36248416 PMCID: PMC9560822 DOI: 10.1155/2022/9707278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 11/07/2022]
Abstract
Background Obesity is a significant public health problem that is characterized by an increase in oxidative stress and enhanced inflammatory responses associated with immune cell invasion of adipose tissues. This study assessed several biochemical abnormalities, apoptosis, oxidative stress status, and associated histological changes in the liver, duodenum, and heart brought on by high-fat diet-induced obesity in rats. It also assessed the mechanistic benefits of curcumin in reversing these inflammatory, metabolic, and histological impairments. Methods Rats were assigned into three groups each including ten rats: the control group (CD), the high-fat diet group (HFD), and the high-fat diet + curcumin (HFDC) group. Serum glucose, insulin, and triglycerides (TAGs) were observed. In addition, apoptosis (indicated by hepatic DNA fragmentation) and oxidative stress status (indicated by hepatic MPO, GSH, and SOD) were assessed. Histopathological examinations included the GIT (liver and duodenum) and heart in addition to quantitative real-time polymerase chain reaction (qRT-PCR) assays of the adipose tissue genetic expressions for inflammatory signaling pathways (TLR4, IL-6, and TNF-α). Results The overall findings showed that the HFD group exhibited significantly higher levels of glucose, TAGs, and insulin than the control group (P < 0.01). The histological abnormalities of the studied organs in the HFD group were paralleled by these biochemical abnormalities, which were strongly associated with increased apoptosis, increased oxidative stress, and increased expression of the inflammatory signaling markers. There were significant improvements in the HFDC group in terms of biochemical, inflammatory, and histological investigations. Conclusions This study's findings concluded that obesity is significantly associated with biochemical and microscopic alterations in many organs. Curcumin exerted potent antitoxic, antioxidant, tissue-protective, and antiobesity effects. Curcumin is recommended to be added to various dietary regimens to prevent or delay the organs' dysfunction among obese people.
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Chen Y, Feng S, Chang Z, Zhao Y, Liu Y, Fu J, Liu Y, Tang S, Han Y, Zhang S, Fan Z. Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease. Nutrients 2022; 14:nu14194013. [PMID: 36235666 PMCID: PMC9571761 DOI: 10.3390/nu14194013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/23/2022] [Accepted: 09/24/2022] [Indexed: 11/26/2022] Open
Abstract
Aims: We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels with all-cause and cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). Methods: We performed a retrospective cohort study based on the US National Health and Nutrition Examination Survey 2001–2016 on adults aged ≥20 years. NAFLD was determined as a US Fatty Liver Index score ≥ 30 in the absence of other liver conditions. Weighted Cox proportional hazards regression models were applied to explore the relationship between serum 25(OH)D levels and mortality. Results: 898 all-cause deaths and 305 cardiovascular deaths were recorded over a median follow-up of 8.7 years. Compared with those in the severe deficiency group (below 25.0 nmol/L), the fully adjusted HRs and 95% CIs of NAFLD patients with sufficient serum 25(OH)D concentrations (≥75.0 nmol/L) were 0.36 (0.22, 0.60) for all-cause mortality and 0.14 (0.07, 0.29) for cardiovascular mortality. Each one-unit increase in the natural log-transformed serum 25(OH)D concentration was related to a 41% lower risk for all-cause deaths (HR = 0.59, 95% CI: 0.46, 0.77) and a 65% lower risk for cardiovascular deaths (HR = 0.35, 95% CI: 0.22, 0.58). Conclusions: Among NAFLD patients, increased serum 25(OH)D levels were independently associated with reduced risk for all-cause and cardiovascular deaths.
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Zhang JJ, Yu HC, Li Y, Zhang YB, Geng TT, Lu Q, Liao YF, Guo KQ, Du L, Ruan HL, Yang K, Liu G, Pan A. Association between serum 25-hydroxy vitamin D concentrations and mortality among individuals with metabolic dysfunction-associated fatty liver disease: a prospective cohort study. Am J Clin Nutr 2022; 116:1409-1417. [PMID: 36107812 DOI: 10.1093/ajcn/nqac260] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/26/2022] [Accepted: 09/13/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The association between serum 25-hydroxy vitamin D (25(OH)D) concentrations and mortality remains unclear among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD). OBJECTIVES To evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD. METHODS The study included 4651 individuals with fatty liver disease (FLD) (3964 had MAFLD and 3968 had NAFLD) from the Third National Health and Nutrition Examination Survey. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of potential confounders. RESULTS Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 years, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HR and 95% CI of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001), and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinearly inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall <0.001; Pnonlinear = 0.003) or NAFLD (Poverall <0.001; Pnonlinear = 0.009), with a threshold effect at around 50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 years (P-interaction = 0.001). CONCLUSIONS This study suggested a nonlinearly inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at around 50.0 nmol/L of serum 25(OH)D.
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Affiliation(s)
- Ji-Juan Zhang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Han-Cheng Yu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yue Li
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yan-Bo Zhang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ting-Ting Geng
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Qi Lu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yun-Fei Liao
- Department of Endocrinology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Kun-Quan Guo
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Liang Du
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Hua-Ling Ruan
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Kun Yang
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Gang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - An Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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Pop TL, Sîrbe C, Benţa G, Mititelu A, Grama A. The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases. Int J Mol Sci 2022; 23:10705. [PMID: 36142636 PMCID: PMC9503777 DOI: 10.3390/ijms231810705] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/24/2022] Open
Abstract
Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.
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Affiliation(s)
- Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Claudia Sîrbe
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Gabriel Benţa
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alexandra Mititelu
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Peng H, Wang M, Pan L, Cao Z, Yao Z, Chen Q, Li Y, Wang Y, Lv W. Associations of serum multivitamin levels with the risk of non-alcoholic fatty liver disease: A population-based cross-sectional study in U.S. adults. Front Nutr 2022; 9:962705. [PMID: 36172527 PMCID: PMC9511103 DOI: 10.3389/fnut.2022.962705] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/22/2022] [Indexed: 11/22/2022] Open
Abstract
Vitamins were closely associated with non-alcoholic fatty liver disease (NAFLD) development, but no study had explored the association of serum multivitamin levels with NAFLD risk. We assessed the association between serum levels of both single-vitamin and multivitamins (VA, VB6, VB9, VB12, VC, VD, and VE) and the risk of NAFLD, using the database of National Health and Nutrition Examination Survey (NHANES) (cycles 2003–2004 and 2005–2006). We employed multivariable logistic regression and weighted quantile sum (WQS) regression models to explore the association of serum multivitamin levels with NAFLD. Among all 2,294 participants, 969 participants with NAFLD were more likely to be male, older, less educated, or have hypertension/high cholesterol/diabetes. After adjustment of covariates, serum VC/VD/VB6/VB9 levels were negatively correlated with NAFLD risk, while serum VA/VE levels were positively correlated with NAFLD risk. In the WQS model, elevated serum VA/VE levels and lowered serum VC/VD/VB6 levels were linearly associated with increased NAFLD risk. There was a non-linear relationship between serum VB9/VB12 levels and NAFLD risk. There were evident associations between serum multivitamin levels and reduced NAFLD risk, which was mainly driven by VD/VB9/VC. In conclusion, our findings suggested that serum multivitamin levels were significantly associated with the risk of NAFLD.
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Affiliation(s)
- Hongye Peng
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Hongye Peng,
| | - Miyuan Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liang Pan
- Phase 1 Clinical Trial Center, Deyang People’s Hospital, Deyang, China
| | - Zhengmin Cao
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ziang Yao
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiuye Chen
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanbo Li
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuhua Wang
- Phase 1 Clinical Trial Center, Deyang People’s Hospital, Deyang, China
| | - Wenliang Lv
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Wenliang Lv,
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Han L, Fu S, Li J, Liu D, Tan Y. Association between grip strength and non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Med (Lausanne) 2022; 9:988566. [PMID: 36091710 PMCID: PMC9458919 DOI: 10.3389/fmed.2022.988566] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 08/03/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The association between grip strength (GS) and non-alcoholic fatty liver disease (NAFLD) has been reported by recent epidemiological studies, however, the results of these studies are inconsistent. This meta-analysis was conducted to collect all available data and estimate the risk of NAFLD among people with low GS, as well as the risk of low GS among patients with NAFLD. METHODS We systematically searched several literature databases including PubMed, Web of Science, Cochrane Library, and Embase from inception to March 2022. These observational studies reported the risk of NAFLD among people with low GS and/or the risk of low GS among patients with NAFLD. Qualitative and quantitative information was extracted, statistical heterogeneity was assessed using the I 2 test, and potential for publication bias was assessed qualitatively by a visual estimate of a funnel plot and quantitatively by calculation of the Begg's test and the Egger's test. RESULTS Of the citations, 10 eligible studies involving 76,676 participants met inclusion criteria. The meta-analysis of seven cross-section studies (69,757 participants) showed that people with low GS had increased risk of NAFLD than those with normal GS (summary OR = 3.32, 95% CI: 1.91-5.75). In addition, the meta-analysis of four studies (14,920 participants) reported that the risk of low GS patients with NAFLD was higher than those in normal people (summary OR = 3.31, 95% CI: 2.45-4.47). CONCLUSION In this meta-analysis, we demonstrated a strong relationship between low GS and NAFLD. We found an increased risk of NAFLD among people with low GS, and an increased risk of lower GS among NAFLD patients. SYSTEMATIC REVIEW REGISTRATION [www.crd.york.ac.uk/prospero], identifier [CRD42022334687].
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Affiliation(s)
- Liu Han
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Shifeng Fu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Jianglei Li
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Deliang Liu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Yuyong Tan
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
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Cao J, Hua L, Zhang S, Tang J, Ke F, Wu Z, Xue G. Serum interleukin-38 levels correlated with insulin resistance, liver injury and lipids in non-alcoholic fatty liver disease. Lipids Health Dis 2022; 21:70. [PMID: 35948957 PMCID: PMC9364532 DOI: 10.1186/s12944-022-01676-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 07/18/2022] [Indexed: 11/18/2022] Open
Abstract
Background Insulin resistance, liver injury and dyslipidemia are reported in non-alcoholic fat liver disease (NAFLD) patients. Interleukin (IL)-38 may take part in the pathophysiology of insulin resistance. Nevertheless, the function of IL-38 in NAFLD is unknown. Herein, we determined whether serum IL-38 level might be utilised as a biochemical marker for diagnosing NAFLD. Methods NAFLD patients and healthy participants (n = 91 each) were enrolled. Circulating serum IL-38 levels were detected using enzyme-linked immunosorbent assay. Other metabolic and inflammatory indices related to NAFLD were also assessed. Results Patients with NAFLD had higher serum IL-38 levels than healthy individuals. Significantly higher serum IL-38 levels were found in patients with severe and moderate NAFLD than in patients with mild NAFLD. IL-38 showed a significant correlation with parameters of insulin resistance, inflammation, and liver enzyme in NAFLD cases. Anthropometric, insulin resistance, inflammatory parameters, lipids and frequency of NAFLD showed significant differences among the serum IL-38 level tertiles. Participants in the 2nd and 3rd tertiles of serum IL-38 levels had a greater risk of NAFLD than those in the 1st tertile. Furthermore, IL-38 ROC curve showed a high area under ROC with 0.861. Conclusions It is possible for serum IL-38 to be a biomarker for NAFLD.
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Affiliation(s)
- Jun Cao
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiujiang University, 17# Lufeng Road, Jiujiang, 332000, Jiangxi Province, China
| | - Lin Hua
- Department of Clinical Laboratory, Jiujiang NO.1 People's Hospital, 48# The South of Taling Road, Jiujiang, 332000, Jiangxi Province, China
| | - Shipei Zhang
- Department of Clinical Laboratory, Jiujiang NO.1 People's Hospital, 48# The South of Taling Road, Jiujiang, 332000, Jiangxi Province, China
| | - Jinping Tang
- Department of Clinical Laboratory, Jiujiang NO.1 People's Hospital, 48# The South of Taling Road, Jiujiang, 332000, Jiangxi Province, China
| | - Fan Ke
- Department of Endocrinology, Jiujiang NO.1 People's Hospital, 48# The South of Taling Road, Jiujiang, 332000, Jiangxi Province, China
| | - Zhouhuan Wu
- Department of pharmacology, School of Medicine, Jiujiang University, 17# Lufeng Road, Jiujiang, 332000, Jiangxi Province, China
| | - Guohui Xue
- Department of Clinical Laboratory, Jiujiang NO.1 People's Hospital, 48# The South of Taling Road, Jiujiang, 332000, Jiangxi Province, China.
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Aggeletopoulou I, Thomopoulos K, Mouzaki A, Triantos C. Vitamin D-VDR Novel Anti-Inflammatory Molecules-New Insights into Their Effects on Liver Diseases. Int J Mol Sci 2022; 23:8465. [PMID: 35955597 PMCID: PMC9369388 DOI: 10.3390/ijms23158465] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 02/05/2023] Open
Abstract
There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D-VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D-VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.
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Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, GR-26504 Patras, Greece;
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, GR-26504 Patras, Greece;
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
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Kim Y, Chang Y, Ryu S, Cho IY, Kwon MJ, Sohn W, Kim MK, Wild SH, Byrne CD. Resolution of, and Risk of Incident Non-alcoholic Fatty Liver Disease With Changes in Serum 25-hydroxy Vitamin D Status. J Clin Endocrinol Metab 2022; 107:e3437-e3447. [PMID: 35460237 DOI: 10.1210/clinem/dgac255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Indexed: 02/06/2023]
Abstract
CONTEXT A protective or causative role of vitamin D status on the risk of nonalcoholic fatty liver disease (NAFLD) remains inconclusive. OBJECTIVE To evaluate the association between changes in serum 25-hydroxyvitamin D [25(OH)D] status during follow-up and the risk of incident NAFLD and resolution of preexisting NAFLD. DESIGN A retrospective cohort study. SETTING Kangbuk Samsung Health Study based on routine health screening examinations. PARTICIPANTS Korean adults (mean age, 36.8 years; range, 18-96 years) who underwent comprehensive health examinations including assessment of serum 25(OH)D levels. MAIN OUTCOME MEASURES The main outcomes were (1) incidence and (2) resolution of NAFLD assessed by liver ultrasound. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs for outcomes according to serum 25(OH)D levels. RESULTS Among 139 599 participants without NAFLD at baseline, 27 531 developed NAFLD during follow-up. Serum 25(OH)D levels were significantly and inversely associated with NAFLD development. Among 48 702 participants with NAFLD at baseline, 13 449 showed NAFLD resolution. Multivariable-adjusted HR (95% CI) for NAFLD resolution comparing 25(OH)D 10 to <20, 20 to <30, and ≥30 ng/mL to <10 ng/mL were 1.09 (1.03-1.15), 1.13 (1.06-1.21), and 1.21 (1.09-1.35), respectively. Additionally, an increase in 25(OH)D levels between baseline and the subsequent visit (median, 1.8 years) was associated with decreased NAFLD incidence, while persistently adequate 25(OH)D levels over time was associated with decreased incidence and increased resolution of NAFLD. CONCLUSIONS Maintaining adequate serum 25(OH)D concentrations may be beneficial for both prevention as well as resolution of NAFLD.
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Affiliation(s)
- Yejin Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - In Young Cho
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Min-Jung Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Sohn
- Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea
| | - Mi Kyung Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health and Care Research Southampton Biomedical Research Center, University Hospital Southampton, Southampton, UK
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Guan Y, Xu Y, Su H, Sun X, Li Y, Wang T. Effect of serum vitamin D on metabolic associated fatty liver disease: a large population-based study. Scand J Gastroenterol 2022; 57:862-871. [PMID: 35170370 DOI: 10.1080/00365521.2022.2039284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several studies have revealed that serum vitamin D is an important factor for metabolic associated fatty liver disease (MAFLD), but there had been no consistent conclusion. METHODS Of 427,507 subjects who underwent health examination, 83,625 who met the inclusion criteria were included in a cross-sectional analysis. Clinical and laboratory data were collected for analysis. MAFLD was diagnosed by abdominal imaging. RESULTS Multivariate linear regression models discovered a negative association between serum vitamin D and MAFLD (OR: 0.92, 95% CI: 0.90 to 0.94, p = .001), after adjusting for other well-identified risk factors. The same result was found when serum vitamin D was handled as a categorical variable (quartile, Q1-Q4) (Q4 vs. Q1, OR: 0.82, 95% CI: 0.77 to 0.87, p < .001), and a significant linear trend was observed (p for trend <.001). After analysis, a nonlinear relationship was detected between serum vitamin D and MAFLD, with an inflection point of 2.23 (44.6 nmol/L or 17.84 ng/mL). The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.16 (1.06 to 1.28) and 0.89 (0.86 to 0.91), respectively. All interactions with MAFLD were not significant for age, sex, diabetes, hypertension, smoking and body mass index (p for interaction = .110, .558, .335, .195, .616 and .401, respectively). CONCLUSIONS There was a nonlinear relationship between serum vitamin D and MAFLD. When the serum vitamin D level was ≥44.6 nmol/L (17.84 ng/mL), a negative correlation between serum vitamin D and MAFLD was detected. Below this level, serum vitamin D might promote the progression of MAFLD.
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Affiliation(s)
- Yaqi Guan
- Department of Nursing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yilun Xu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huang Su
- Department of Gastroenterology, Wenzhou Central Hospital, The dingli clinical institute of Wenzhou Medical University, Wenzhou, China
| | - Xuecheng Sun
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yanxuan Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Tingting Wang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Song YP, Lv JW, Zhao Y, Chen X, Zhang ZC, Fan YJ, Zhang C, Gao L, Huang Y, Wang H, Xu DX. DNA hydroxymethylation reprogramming of β-oxidation genes mediates early-life arsenic-evoked hepatic lipid accumulation in adult mice. JOURNAL OF HAZARDOUS MATERIALS 2022; 430:128511. [PMID: 35739688 DOI: 10.1016/j.jhazmat.2022.128511] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 02/10/2022] [Accepted: 02/15/2022] [Indexed: 06/15/2023]
Abstract
The metabolic disorders are becoming an epidemic disease endangering public health in countries. Environmental factors are mainly reason for the growth of metabolic disorders. Previous research suggests that DNA methylation is a potential mechanism. Recently, it has been reported that DNA hydroxymethylation is also a stable marker of epigenetic reprogramming. Hence, the study aims to investigate whether DNA hydroxymehylation mediates early-life environmental stress-evoked metabolic disorder in adulthood. Mice were orally administered with arsenic (As), an environmental stressor, throughout pregnancy. We show that early-life As exposure induces glucose intolerance and hepatic lipid accumulation in adulthood. Early-life As exposure alters epigenetic reprogramming and expression of lipid metabolism-related genes including β-oxidation-specific genes in adulthood. Of interest, early-life As exposure alters epigenetic reprogramming of hepatic lipid metabolism partially through reducing DNA hydroxymethylation modification of β-oxidation-related genes in developing liver. Mechanistically, early-life As exposure suppresses ten-eleven translocation (TET) activity through downregulating isocitrate dehydrogenases (Idh) and reducing alpha-ketoglutarate (α-KG) content in the developing liver. In addition, early-life As exposure inhibits TET1 binding to CpG-rich fragments of β-oxidation-related genes in developing liver. This study provide novel evidence that early-life environmental stress leads to later life metabolic disorders by altering hepatic DNA hydroxymethylation reprogramming.
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Affiliation(s)
- Ya-Ping Song
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Jin-Wei Lv
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Ying Zhao
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Xu Chen
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Zhi-Cheng Zhang
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Yi-Jun Fan
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Cheng Zhang
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Lan Gao
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Yichao Huang
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - Hua Wang
- Department of Toxicology, Anhui Medical University, Hefei 230032, China
| | - De-Xiang Xu
- Department of Toxicology, Anhui Medical University, Hefei 230032, China.
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Rahimpour Z, Hoseini R, Behpour N. Effect of Short-term Vitamin D Supplementation on the Alterations of Glycemic Variables in Response to Exhaustive Eccentric Exercise in Patients with Non-alcoholic Fatty Liver. Middle East J Dig Dis 2022; 14:229-234. [PMID: 36619147 PMCID: PMC9489312 DOI: 10.34172/mejdd.2022.277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 02/19/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND: Exhaustive eccentric exercise (EEE), along with a positive role in weight loss and physiological adaptation, increases liver enzymes and disturbs glucose homeostasis. Many studies have been considered to neutralize the adverse effects of EEE, including vitamin D (Vit D) supplementation. The present study aimed to investigate the effect of short-term Vit D supplementation on the alteration of glycemic variables in response to EEE in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In this clinical trial, 22 overweight women with NAFLD were randomly assigned to control (C; n=11) and experimental (Exp; n=11) groups. C group received a lactose placebo daily with the same color, shape, and warmth percentage; Exp group received 2000 IU of Vit D daily for 6 weeks (42 days). Blood samples were taken to measure the liver enzymes, lipid profile, and Vit D levels alteration at four stages: Pre1(before the first EEE session), post 1 (after the first EEE session), pre 2 (before the second EEE session), and post 2 (after the second EEE session). Repeated measures ANOVA and independent t test were used to analyze the data using SPSS software (version 26) at a significance level of P < 0.05. RESULTS: The results show a significant increase in glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) levels in both C and Exp groups following the EEE (comparing pre 1 and post 1). Also, after 6 weeks of Vit D supplementation, glucose, insulin, and HOMA-IR increased significantly in both C (P = 0.001, P = 0.001, and P = 0.001, respectively) and Exp (P = 0.001, P = 0.001, and P = 0.001, respectively) groups following EEE (comparison of pre 2 and post 2). However, these increases were significantly lower in Exp group compared with the C group (comparing post 2). CONCLUSION: Short-term Vit D supplementation downregulates the increased glucose, insulin, and insulin resistance induced by EEE in patients with NAFLD.
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Affiliation(s)
- Zahra Rahimpour
- MSc of Exercise Physiology, Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
| | - Rastegar Hoseini
- Assistant Professor of Exercise Physiology, Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran,Corresponding Author: Rastegar Hoseini, PhD Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran, P.O.Box. 6714414971 Tel: + 98 83 34283267 Fax: + 98 83 34279245
| | - Nasser Behpour
- Associate Professor of Exercise Physiology, Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
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El Amrousy D, Abdelhai D, Shawky D. Vitamin D and nonalcoholic fatty liver disease in children: a randomized controlled clinical trial. Eur J Pediatr 2022; 181:579-586. [PMID: 34459959 DOI: 10.1007/s00431-021-04243-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/13/2021] [Accepted: 08/18/2021] [Indexed: 02/05/2023]
Abstract
Vitamin D is reported to have anti-inflammatory and insulin-sensitizing effects, yet vitamin D effects on hepatic fat content in children with nonalcoholic fatty liver disease (NAFLD) are not studied sufficiently. We aimed to evaluate the role of vitamin D supplementation on the hepatic fat content and NAFLD progression in children. This randomized controlled clinical trial was performed on 109 children with biopsy-proven NAFLD; only 100 patients completed the study. Patients were randomly assigned into two groups: the treatment group who received 2000 IU/day vitamin D for 6 months and the control group who received a placebo. Anthropometric measurements, vitamin D levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood glucose (FBG), fasting blood insulin level (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), and serum calcium level were measured at the beginning and the end of the study. Liver biopsy was taken before and at the end of the study for all included children. There was a significant improvement of the hepatic steatosis and lobular inflammation by liver biopsy in the treatment group after treatment. However, there was no significant effect on the hepatocyte ballooning or hepatic fibrosis. There were significant decrease of AST, ALT, TG, LDL, FBG, FBI, and HOMA-IR and significant increase of vitamin D levels and HDL in the treatment group compared to the placebo group (P < 0.05).Conclusion: Vitamin D supplementation was found to be beneficial in the treatment of NAFLD in children.Trial registration: www.pactr.org , PACTR201710002634203. What is Known: • Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in pediatrics. • Several studies reported a negative association between low serum vitamin D level and grades of NAFLD. What is New: • Vitamin D supplementation has significantly decreased hepatic steatosis and lobular inflammation and improved the grades of NAFLD in children, confirmed by liver biopsy, but no effect on hepatocyte ballooning or fibrosis was observed. • Adjuvant vitamin D supplementation is recommended in children with NAFLD.
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Affiliation(s)
- Doaa El Amrousy
- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
- Tanta University Hospital, El Motasem Street No. 6, Tanta, Egypt.
| | - Dina Abdelhai
- Tanta University Hospital, El Motasem Street No. 6, Tanta, Egypt
- Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Dina Shawky
- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Egypt
- Tanta University Hospital, El Motasem Street No. 6, Tanta, Egypt
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Tao T, Kobelski MM, Saini V, Demay MB. Adipose-specific VDR Deletion Leads to Hepatic Steatosis in Female Mice Fed a Low-Fat Diet. Endocrinology 2022; 163:6457073. [PMID: 34878523 PMCID: PMC10061053 DOI: 10.1210/endocr/bqab249] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Indexed: 02/03/2023]
Abstract
Risk factors for nonalcoholic hepatic steatosis include obesity and vitamin D deficiency which commonly coexist. Thus, the role of vitamin D signaling in the prevention of hepatic steatosis in the absence of obesity or a "Western" high-fat diet is unclear. These studies were performed to address the role of the adipocyte vitamin D receptor (VDR) in the prevention of hepatic steatosis in mice fed a chow diet containing 5% fat by weight. Female mice with adipocyte VDR ablation (Adipoq-Cre; VDRflox/flox) exhibited a mild increase in weight gain at age 70 days, accompanied by an increase in visceral white adipose tissue (VAT) weight. While they did not exhibit evidence of hepatic inflammation or fibrosis, an increase in hepatic lipid content was observed. This was accompanied by an increase in the hepatic expression of genes involved in fatty acid transport and synthesis, as well as fatty acid oxidation. Markers of hepatic inflammation and fibrosis were unaffected by adipocyte VDR ablation. Consistent with the increase in VAT weight in the Adipoq-Cre; VDRflox/flox mice, higher levels of transcripts encoding adipogenesis-related genes were observed in VAT. In contrast to other models of impaired vitamin D signaling studied in the setting of a high-fat or "Western" diet, the Adipoq-Cre; VDRflox/flox mice do not exhibit hepatic inflammation or fibrosis. These findings suggest that the adipocyte VDR regulates hepatic lipid accumulation, but in the absence of obesity or a high-fat diet, is not required to prevent hepatic inflammation or fibrosis.
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Affiliation(s)
- Tao Tao
- Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
- Harvard Medical School, Boston, Massachusetts 02115, USA
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Margaret M Kobelski
- Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
| | - Vaibhav Saini
- Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
- Harvard Medical School, Boston, Massachusetts 02115, USA
| | - Marie B Demay
- Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
- Harvard Medical School, Boston, Massachusetts 02115, USA
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Li KP, Yuan M, Wu YL, Pineda M, Zhang CM, Chen YF, Chen ZQ, Rong XL, Turnbull JE, Guo J. A high-fat High-fructose Diet Dysregulates the Homeostatic Crosstalk Between Gut Microbiome, Metabolome and Immunity in an Experimental Model of Obesity. Mol Nutr Food Res 2022; 66:e2100950. [PMID: 35072983 DOI: 10.1002/mnfr.202100950] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/30/2021] [Indexed: 11/07/2022]
Abstract
SCOPE Ample evidence supports the prominent role of gut-liver axis in perpetuating pathological networks of high-fat high-fructose (HFF) diet induced metabolic disorders, however, the molecular mechanisms are still not fully understood. Herein, we aim to present a holistic delineation and scientific explanation for the crosstalk between the gut and liver, including the potential mediators involved in orchestrating the metabolic and immune systems. METHODS An experimental obesity associated metaflammation rat model was induced with a HFF diet. An integrative multi-omics analysis was then performed. Following the clues illustrated by the multi-omics discoveries, putative pathways were subsequently validated by RT-qPCR and Western blotting. RESULTS HFF diet led to obese phenotypes in rats, as well as histopathological changes. Integrated omics analysis showed there existed a strong interdependence among gut microbiota composition, intestinal metabolites and innate immunity regulation in the liver. Some carboxylic acids might contribute to gut-liver communication. Moreover, activation of the hepatic LPS-TLR4 pathway in obesity was confirmed. CONCLUSIONS HFF-intake disturbs gut flora homeostasis. Crosstalk between gut microbiota and innate immune system mediated hepatic metaflammation in obese rats, associated with LPS-TLR4 signaling pathway activation. Moreover, α-hydroxyisobutyric acid and some other organic acids may play a role as messengers in the liver-gut axis. High-fat high-fructose diet (HFF) induces obesity associated chronic inflammation; HFF dysregulates the rat intestinal metabolome and gut microbiota composition; HFF impacts hepatic expression of genes involved in innate immunity; Modulation of gut microbiota composition and innate immunity are connected partly via TLR4 signalling; Small molecular carboxylic acids are potential mediators of gut-liver axis communication in chronic obesity. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Kun-Ping Li
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Min Yuan
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Yong-Lin Wu
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Miguel Pineda
- Institute of infection, immunity & inflammation, University of Glasgow, University Place, Glasgow, G12 8TA, UK
| | - Chu-Mei Zhang
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Yan-Fen Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Zhi-Quan Chen
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Xiang-Lu Rong
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Jeremy E Turnbull
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
| | - Jiao Guo
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
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Zhao X, Deng C, Li Z, Jia Y, Chen S. Monocyte/High-Density Lipoprotein Cholesterol Ratio Predicts Vitamin D Deficiency in Male Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2022; 15:2455-2466. [PMID: 35982762 PMCID: PMC9380827 DOI: 10.2147/dmso.s376127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/28/2022] [Indexed: 04/20/2023] Open
Abstract
PURPOSE This study aimed to investigate the relationship between monocyte/high-density lipoprotein cholesterol ratio (MHR) and 25-hydroxyvitamin D [25(OH) D] level in patients with type 2 diabetes mellitus (T2DM), the risk factors for vitamin D deficiency, and the clinical value of MHR as a predictor of vitamin D deficiency in this population. PATIENTS AND METHODS This was a cross-sectional study of 260 patients with T2DM from May 2021 to October 2021. Based on internationally used criteria for defining vitamin D levels, the patients were divided according to sex and levels of vitamin D into the following four groups: Group A1 (male patients with vitamin D levels <20 ng/mL), group A2 (male patients with vitamin D levels ≥20 ng/mL), group B1 (female patients with vitamin D levels <20 ng/mL), and group B2 (female patients with vitamin D levels≥20 ng/mL). The MHR was calculated as a monocyte/high-density cholesterol lipoprotein ratio. RESULTS The vitamin D level was independently and negatively correlated with the MHR in male patients with T2DM, but not in female patients. The MHR was an independent risk factor and predictor for the development of vitamin D deficiency in male patients, but not in female patients, with T2DM. High-density lipoprotein (HDL) was an independent protective factor for vitamin D deficiency in female patients with T2DM. CONCLUSION This study suggested that the MHR was a new marker for predicting vitamin D deficiency in male patients with T2DM. Alleviating inflammation, improving lipid metabolism, and increasing HDL levels in patients with T2DM might help improve vitamin D levels, which might be important for preventing and managing T2DM. The MHR might help as a new marker to predict vitamin D deficiency in China, where primary hospitals lack the capacity for vitamin D testing on a large scale.
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Affiliation(s)
- Xuetong Zhao
- Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
| | - Chenqian Deng
- Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
| | - Zelin Li
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Yujiao Jia
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Shuchun Chen
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China
- Hebei Key Laboratory of Metabolic Diseases, Shijiazhuang, People’s Republic of China
- Correspondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email
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Bima A, Eldakhakhny B, Nuwaylati D, Alnami A, Ajabnoor M, Elsamanoudy A. The Interplay of Vitamin D Deficiency and Cellular Senescence in The Pathogenesis of Obesity-Related Co-Morbidities. Nutrients 2021; 13:nu13114127. [PMID: 34836382 PMCID: PMC8618094 DOI: 10.3390/nu13114127] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 11/09/2021] [Accepted: 11/15/2021] [Indexed: 01/10/2023] Open
Abstract
This scoping review aims to clarify the interplay between obesity, vitamin D deficiency, cellular senescence, and obesity-related metabolic consequences, mainly subclinical atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Obesity is a significant global health problem that involves cellular, environmental, behavioral, and genetic elements. The fundamental cause of obesity throughout all life stages is an energy imbalance, and its consequences are countless and, foremost, very common. Obesity has been comprehensively studied in the literature given its association with low serum vitamin D, with many proposed mechanisms linking the two conditions. Moreover, markers of exaggerated cellular senescence have been proven to accumulate in obese individuals. Subclinical atherosclerosis initiates an early stage that ends in serious cardiac events, and obesity, low vitamin D, and senescent cells largely contribute to its associated chronic low-grade inflammation. Furthermore, NAFLD signifies the hepatic manifestation of metabolic syndrome, and studies have highlighted the important role of obesity, vitamin D deficiency, and cellular senescence in its development. Therefore, we outlined the most important mechanisms tying these conditions to one another.
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Affiliation(s)
- Abdulhadi Bima
- Department of Clinical Biochemistry, Faculty of Medicine, King AbdulAziz University, Jeddah 21465, Saudi Arabia; (A.B.); (B.E.); (A.A.); (M.A.)
| | - Basmah Eldakhakhny
- Department of Clinical Biochemistry, Faculty of Medicine, King AbdulAziz University, Jeddah 21465, Saudi Arabia; (A.B.); (B.E.); (A.A.); (M.A.)
| | - Dina Nuwaylati
- Department of Clinical Biochemistry, Faculty of Medicine, University of Jeddah, Jeddah 21959, Saudi Arabia;
| | - Abrar Alnami
- Department of Clinical Biochemistry, Faculty of Medicine, King AbdulAziz University, Jeddah 21465, Saudi Arabia; (A.B.); (B.E.); (A.A.); (M.A.)
| | - Mohammed Ajabnoor
- Department of Clinical Biochemistry, Faculty of Medicine, King AbdulAziz University, Jeddah 21465, Saudi Arabia; (A.B.); (B.E.); (A.A.); (M.A.)
| | - Ayman Elsamanoudy
- Department of Clinical Biochemistry, Faculty of Medicine, King AbdulAziz University, Jeddah 21465, Saudi Arabia; (A.B.); (B.E.); (A.A.); (M.A.)
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
- Correspondence: ; Tel.: +966-59-506-2375
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Licata A, Zerbo M, Como S, Cammilleri M, Soresi M, Montalto G, Giannitrapani L. The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement? Nutrients 2021; 13:4014. [PMID: 34836267 PMCID: PMC8620546 DOI: 10.3390/nu13114014] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/28/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022] Open
Abstract
Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. More specific knowledge about the role of vitamins in liver disease is currently emerging from various results and recent evidence. The most significant benefits in this area may be observed when improved vitamin intake is combined with a pharmacological treatment that may also affect the progression of the liver disease, especially in the case of liver tumors. However, further studies are needed.
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Affiliation(s)
- Anna Licata
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Maddalena Zerbo
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Silvia Como
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Marcella Cammilleri
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Maurizio Soresi
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Giuseppe Montalto
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Lydia Giannitrapani
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
- Institute for Biochemical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy
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Kulkarni S, Naz N, Gu H, Stoll JM, Thompson MD, DeBosch BJ. A clinical model to predict fibrosis on liver biopsy in paediatric subjects with nonalcoholic fatty liver disease. Clin Obes 2021; 11:e12472. [PMID: 34106515 PMCID: PMC8928096 DOI: 10.1111/cob.12472] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/09/2021] [Accepted: 05/28/2021] [Indexed: 12/19/2022]
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) in children is rapidly increasing. Liver fibrosis is a poor prognostic feature that independently predicts cirrhosis. The time that intercedes the first medical encounter and biopsy is rate-limiting to multi-modal treatment. This study aimed to identify non-invasive parameters to predict advanced NAFLD and fibrosis. We conducted a single-center, retrospective 10-year analysis of 640 paediatric patients who underwent liver biopsy. 55 patients, age 3-21 years, had biopsy-confirmed NAFLD. We assessed primary outcomes, NAFLD activity score (NAS) and fibrosis scores, against non-invasive parameters by linear regression, by using binary cutoff values, and by a multivariate logistic regression fibrosis prediction model. NAS correlated with platelets and female sex. Fibrosis scores correlated with platelet counts, gamma glutamyl transferase (GGT), and ultrasound shear wave velocity. 25-hydroxy-vitamin D and GGT differentiated mild versus moderate-to-advanced fibrosis. Our multivariate logistical regression model-based scoring system predicted F2 or higher (parameters: BMI%, vitamin D, platelets, GGT), with sensitivity and specificity of 0.83 and 0.95 (area under the ROC curve, 0.944). We identify a clinical model to identify high-risk patients for expedited biopsy. Stratifying patients to abbreviate time-to-biopsy can attenuate delays in aggressive therapy for high-risk patients.
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Affiliation(s)
- Sakil Kulkarni
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Nadia Naz
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Hongjie Gu
- Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
| | - Janis M. Stoll
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Michael D. Thompson
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Digestive Diseases Research Center (DDRCC), Washington University School of Medicine, St. Louis, MO, USA
| | - Brian J. DeBosch
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Digestive Diseases Research Center (DDRCC), Washington University School of Medicine, St. Louis, MO, USA
- Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA
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Xiu L, Jiang T, Yao XA, Wen Z. Correlation Between 25 Hydroxyvitamin D Levels and Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study. Int J Gen Med 2021; 14:3099-3107. [PMID: 34234538 PMCID: PMC8257066 DOI: 10.2147/ijgm.s319449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 06/15/2021] [Indexed: 12/20/2022] Open
Abstract
Purpose We aimed to analyze the serum vitamin D level in Chinese patients with type 2 diabetes mellitus (T2DM) and discuss its correlation with nonalcoholic fatty liver disease (NAFLD). Patients and Methods A total of 300 patients with T2DM (92 patients without NAFLD and 208 patients with NAFLD) were enrolled, and 25-hydroxyvitamin D [25-(OH)D] levels were compared between the two groups. Second, the NAFLD fibrosis score (NFS) and fatty liver index (FLI) were used to group patients with T2DM complicated by NAFLD, and the differences in serum 25-(OH)D in patients with different degrees of liver fibrosis were compared. Third, multiple regression analysis was used to analyze the independent predictors of liver fibrosis in patients with T2DM complicated by NAFLD. Results The level of 25-(OH)D in patients with T2DM complicated by NAFLD was significantly lower than that in patients with T2DM alone. Based on the NFS and FLI, the 25-(OH)D level of the hepatic fibrosis subgroup was significantly lower than that of the subgroup without liver fibrosis. 25-(OH)D was found to be an independent predictor of liver fibrosis in patients with T2DM complicated by NAFLD. Conclusion The serum 25-(OH)D level in patients with T2DM complicated by NAFLD was significantly reduced, and the 25-(OH)D level showed a gradual downward trend with the degree of liver fibrosis. Low concentrations of 25-(OH)D may be indicative of the degree of liver fibrosis in diabetic patients.
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Affiliation(s)
- Lei Xiu
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Tao Jiang
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Xiao-Ai Yao
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Zhen Wen
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
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Heo NJ, Park HE, Yoon JW, Kwak MS, Yang JI, Chung SJ, Yim JY, Chung GE. The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter. J Clin Med 2021; 10:jcm10122611. [PMID: 34199258 PMCID: PMC8231966 DOI: 10.3390/jcm10122611] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). METHODS We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. RESULTS Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47-1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44-0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44-0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31-0.87 in Q4 vs. Q1). CONCLUSIONS Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.
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Affiliation(s)
- Nam Ju Heo
- Department of Nephrology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Korea;
| | - Hyo Eun Park
- Department of Cardiology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Korea;
| | - Ji Won Yoon
- Department of Endocrinology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Korea;
| | - Min-Sun Kwak
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Jong In Yang
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Su Jin Chung
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Jeong Yoon Yim
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Goh Eun Chung
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
- Correspondence: ; Tel.: +82-(0)2-2112-5741; Fax: +82-(0)2-2112-5635
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