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Zhang W, Gao B, Wang Y, Cao Y, Wang J. The relationship between hepatic steatosis index and hypertension: NHANES 2011-2018. BMC Cardiovasc Disord 2025; 25:289. [PMID: 40247193 PMCID: PMC12004791 DOI: 10.1186/s12872-025-04744-2] [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: 01/25/2025] [Accepted: 04/07/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND The Hepatic Steatosis Index (HSI) serves as a non-invasive indicator for assessing liver fat accumulation. Its potential association with hypertension has garnered increasing attention, as metabolic dysfunctions, including hepatic steatosis, may contribute to elevated blood pressure via mechanisms such as insulin resistance and chronic inflammation. METHODS Utilizing data from the NHANES database (2011-2018), the HSI was calculated on the basis of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and BMI.The association between HSI and hypertension was assessed by univariate analysis, weighted multivariate Logistic regression, and restricted cubic spline (RCS) models. Subgroup analyses were performed to increase the reliability of the data. RESULTS This cross-sectional study analysed data from 17,501 adults (NHANES 2011-2018) to assess the association between HSI and hypertension. Of these, 9,890 (56.51%) were diagnosed with hypertension.In the unadjusted model, HSI demonstrated a statistically significant correlation with hypertension, showing an odds ratio (OR) of 1.05 (95% confidence interval: 1.04-1.06).After adjustment for potential confounders, a higher prevalence of hypertension was observed in participants in the upper HSI quartiles (Q3 and Q4), with corresponding ORs of 2.29 (95% CI: 2.29-2.63) and 4.03 (95% CI: 3.42-4.74), respectively. RCS analysis revealed a U-shaped non-linear relationship between HSI and hypertension (P < 0.001), indicating that while hypertension risk primarily escalated with increasing HSI, a modest risk elevation was also detected at lower HSI levels. This suggests that both excessive liver fat accumulation (indicated by a high HSI) and underlying metabolic disorders (such as malnutrition or sarcopenia) may contribute to hypertension risk in individuals with unexpectedly low HSI. Subgroup analyses identified significant interactions in relation to education, cancer, and diabetes mellitus (p for interaction < 0.05), whereas no significant interactions were observed in other stratifications. CONCLUSION This study found a U-shaped relationship between the hepatic steatosis index (HSI) and the risk of hypertension. Although the HSI shows potential as a practical screening tool in primary care, further longitudinal studies are needed to establish causality and explore the complex bidirectional pathways involved. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Wenxuan Zhang
- Acupuncture and moxibustion and Massage College of Anhui University of Chinese Medicine, HF, China
| | - Bing Gao
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China.
| | - Yaping Wang
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China
| | - Yuxiang Cao
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China
| | - Jing Wang
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China.
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, HF, China.
- Key Laboratory of Xin'an Medical Education Department, HF, China.
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Sun Y, Miao X, Hu M, Xie X, Liu S, Song Z, Deng J, Xu F, Li M, He Y, Leng S. Remnant cholesterol and its variability independent of low density lipoprotein cholesterol predict metabolic dysfunction associated steatotic liver disease. Sci Rep 2025; 15:4455. [PMID: 39910118 PMCID: PMC11799198 DOI: 10.1038/s41598-025-88000-9] [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: 08/12/2024] [Accepted: 01/23/2025] [Indexed: 02/07/2025] Open
Abstract
This study aimed to determine whether remnant cholesterol (RC) and its variability can predict the onset of metabolic dysfunction-associated steatotic liver disease (MASLD) independently of low-density lipoprotein cholesterol (LDL-C) levels. A longitudinal cohort study involving 43,065 participants who underwent at least two physical examinations was conducted. This study used Cox proportional hazards models to assess the relationships among RC quartile levels (Q1-Q4), visit-to-visit variability, and the risk of MASLD. This variability was quantified using several metrics: standard deviation (SD), logSD, average real variability (ARV), logARV, mean absolute deviation (MAD), and logMAD. Concurrently, this study utilized a combined analysis of RC and LDL-C groups to assess the independent risk of MASLD associated with RC. During a mean visit-to-visit of 3.19 years (SD 2.06 years), 8374 patients (19.45%) developed MASLD. Compared with Q1, Q4 was associated with a significantly greater risk of MASLD (hazard ratio [HR] 1.309, 95% confidence interval [CI] 1.220-1.403, P < 0.001). The fully adjusted Cox model revealed that the HRs of SD, logSD, ARV, logARV, MAD and logMAD were 1.400 (95% CI 1.305-1.502), 1.278 (95% CI 1.188-1.374), 1.152 (95% CI 1.079-1.229), 1.183 (95% CI 1.140-1.227), 1.578 (95% CI 1.433-1.737) and 1.263 (95% CI 1.175-1.358), respectively. In both LDL-C subgroups (≥ 3.4 mmol/L and < 3.4 mmol/L), high baseline RC was associated with elevated MASLD risk (HR 1.208, 95% CI 1.148-1.270, P < 0.001; HR 1.246, 95% CI 1.129-1.374, P < 0.001). RC levels were independently associated with MASLD in healthy individuals, irrespective of LDL-C level. The variability of RC during visit-to-visit periods provides a predictive marker for identifying individuals at heightened risk of MASLD.
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Affiliation(s)
- Yuting Sun
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Xinlei Miao
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
| | - Manling Hu
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Xiaoling Xie
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Shuang Liu
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Ziping Song
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Jiayi Deng
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Fei Xu
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Meng Li
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Yangxuan He
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Song Leng
- Health Management Center, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning, China.
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China.
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El‐Kassas M, Mostafa H, Abdellatif W, Shoman S, Esmat G, Brahmania M, Liu H, Lee SS. Lubiprostone Reduces Fat Content on MRI-PDFF in Patients With MASLD: A 48-Week Randomised Controlled Trial. Aliment Pharmacol Ther 2025; 61:628-635. [PMID: 39744921 PMCID: PMC11754939 DOI: 10.1111/apt.18478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 06/01/2024] [Accepted: 12/23/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND AND AIMS The laxative lubiprostone has been shown to decrease intestinal permeability. We aimed to assess the safety and efficacy of lubiprostone administered for 48 weeks in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). APPROACH AND RESULTS A randomised placebo-controlled trial was conducted in a specialised MASLD outpatient clinic at the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt. The recruited patients had radiological evidence of MASLD along with other criteria for diagnosis. Eligible patients were randomly assigned to receive either placebo or lubiprostone 24 μg orally twice daily for 48 weeks. The liver fat content was quantified by magnetic resonance imaging estimated proton density fat fraction (MRI-PDFF). Between November 2020 and February 2023, 176 patients were screened, of whom 116 were eligible. Fifty-nine patients were randomised to receive placebo, while 57 patients were randomised to receive lubiprostone. Due mostly to patient dropout (i.e., loss to follow-up), complete data were available for 40 patients in each group. Compared with placebo group, 48-week lubiprostone treatment significantly reduced fat quantity (p = 0.04). Despite a significant reduction in body weight in the control group, no significant difference was found between both groups regarding fibrosis score by transient elastography or in serum ALT levels. One patient in the lubiprostone group developed severe diarrhoea requiring treatment stoppage. No other serious adverse events occurred. CONCLUSION Lubiprostone was well tolerated and reduced liver fat content as measured by MRI-PDFF in patients with MASLD over 48 weeks. Lubiprostone appears promising to treat MASLD and warrants more extensive studies to confirm such efficacy. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT05768334.
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Affiliation(s)
- Mohamed El‐Kassas
- Endemic Medicine Department, Faculty of MedicineHelwan UniversityCairoEgypt
- Liver Disease Research Center, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
- Steatotic Liver Disease Study Foundation in Middle East and North Africa (SLMENA)CairoEgypt
| | - Hala Mostafa
- Endemic Medicine Department, Faculty of MedicineHelwan UniversityCairoEgypt
| | - Wessam Abdellatif
- Radiology DepartmentNational Hepatology & Tropical Medicine Research Institute (NHTMRI)CairoEgypt
| | - Sohier Shoman
- Gastroenterology and Hepatology DepartmentNational Hepatology & Tropical Medicine Research Institute (NHTMRI)CairoEgypt
| | - Gamal Esmat
- Hepatology and Endemic Medicine Department, Faculty of MedicineCairo UniversityCairoEgypt
| | - Mayur Brahmania
- Liver UnitUniversity of Calgary Cumming School of MedicineCalgaryAlbertaCanada
| | - Hongqun Liu
- Liver UnitUniversity of Calgary Cumming School of MedicineCalgaryAlbertaCanada
| | - Samuel S. Lee
- Liver UnitUniversity of Calgary Cumming School of MedicineCalgaryAlbertaCanada
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Fu Y, Jiang C, Li Z, Shi X, Lv P, Zhang J. Association between the composite dietary antioxidant index and non-alcoholic fatty liver disease: evidence from National Health and Nutrition Examination Survey 2005-2016. Front Nutr 2025; 12:1473487. [PMID: 39917746 PMCID: PMC11798779 DOI: 10.3389/fnut.2025.1473487] [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: 07/31/2024] [Accepted: 01/06/2025] [Indexed: 02/09/2025] Open
Abstract
Importance Oxidative stress contributes to the progression of non-alcoholic fatty liver disease (NAFLD). Antioxidants from food can reduce NAFLD incidence, and the Composite Dietary Antioxidant Index (CDAI) measures total antioxidant capacity (TAC). However, the relationship between CDAI and NAFLD in the US adult population remains unclear. Objective To assess whether CDAI is associated with NAFLD in US adults. Design setting and participants This population-based cross-sectional study used data on US adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 cycles. Data were analyzed from January to February 2024. Exposures CDAI obtained from the dietary intake questionnaire. Main outcomes and measures The main outcome was NAFLD which defined by the US fatty liver score (USFLI) ≥30. Sampling weights were calculated according to NHANES guidelines. Results Among 9,746 adults included in this study [mean age, 48.3 years; 4,662 (47.6%) males], 3,324 (33.0%) were classified as having NAFLD using USFLI. In the fully adjusted of multivariable logistic regression, CDAI was negatively associated with NAFLD (odds ratio [OR], 0.95; 95% CI, 0.93-0.98). Furthermore, individuals in the highest quartile of CDAI were 34% less likely to have NAFLD compared to those in the lowest quartile (OR, 0.66; 95% CI, 0.52-0.85). In subgroup analyses, CDAI was inversely associated with NAFLD among participants with a BMI <25 (OR, 0.89; 95% CI, 0.83-0.95) and without metabolic syndrome (OR, 0.93; 95% CI, 0.91-0.96). The interaction tests revealed significant differences in these subgroups (P for interaction = 0.04 for BMI and 0.003 for metabolic syndrome). Sensitivity analyses confirmed this association using the hepatic steatosis index (HSI) to define NAFLD, applying unweighted logistic regression, adjusting for physical activity or after excluding non-Hispanic Black participants, and after excluding medications known for their potential hepatotoxic effects. Conclusions and relevance In this cross-sectional study based on six cycles (2005-2016) of the NHANES, CDAI was negatively associated with NAFLD in US adult population. This association highlights the potential for dietary interventions to reduce NAFLD incidence and underscores the need for future research, including clinical trials and mechanistic studies, to further explore the role of dietary antioxidants in NAFLD prevention and management.
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Affiliation(s)
- Yidian Fu
- Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China
- Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Chao Jiang
- Department of Psychosomatic Medicine, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Zonglin Li
- Department of Medical Laboratory, Liaocheng Hospital of Traditional Chinese Medicine, Liaocheng, Shandong, China
| | - Xiangyun Shi
- College of Geography and Resources, Sichuan Normal University, Chengdu, China
| | - Peiyuan Lv
- Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China
- Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Jingbo Zhang
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Wang YH, Chung CH, Huang TY, Chang CF, Yang CW, Chien WC, Cheng YC. Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study. Intest Res 2025; 23:76-84. [PMID: 38373704 PMCID: PMC11834356 DOI: 10.5217/ir.2023.00078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 12/07/2023] [Accepted: 12/22/2023] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND/AIMS Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. METHODS This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. RESULTS Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn's disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). CONCLUSIONS Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.
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Affiliation(s)
- Ying-Hsiang Wang
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Hsiang Chung
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chao-Feng Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Wei Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wu-Chien Chien
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Chiao Cheng
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Balestra F, De Luca M, Panzetta G, Depalo N, Rizzi F, Mastrogiacomo R, Coletta S, Serino G, Piccinno E, Stabile D, Pesole PL, De Nunzio V, Pinto G, Cerabino N, Di Chito M, Notarnicola M, Shahini E, De Pergola G, Scavo MP. An 8-Week Very Low-Calorie Ketogenic Diet (VLCKD) Alters the Landscape of Obese-Derived Small Extracellular Vesicles (sEVs), Redefining Hepatic Cell Phenotypes. Nutrients 2024; 16:4189. [PMID: 39683581 DOI: 10.3390/nu16234189] [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: 11/04/2024] [Revised: 11/29/2024] [Accepted: 11/30/2024] [Indexed: 12/18/2024] Open
Abstract
Background. Very low-calorie ketogenic diets (VLCKD) are an effective weight-loss strategy for obese individuals, reducing risks of liver conditions such as non-alcoholic steatohepatitis and fibrosis. Small extracellular vesicles (sEVs) are implicated in liver fibrosis by influencing hepatic cell phenotypes and contributing to liver damage. This study investigates sEVs derived from serum of 60 obese adults categorized into low fibrosis risk (LR) and intermediate/high fibrosis risk (IHR) groups based on FibroScan elastography (FIB E scores, limit value 8 kPa) and all participants underwent an 8-week VLCKD intervention. Methods. The study examines the impact of these sEVs on fibrosis markers, inflammation, and autophagy in a hepatocyte cell line (HEPA-RG) using bioinformatics, RNA sequencing, lipidomics, RT-PCR, and Western blotting before (T0) and after (T1) VLCKD. Results. sEVs from LR patients post-VLCKD reduced fibrosis related gene expression (e.g., ACTA2) and enhanced proteins associated with regeneration and inflammation (e.g., HDAC6). Conversely, sEVs from IHR patients increased fibrosis and inflammation related gene expression (PIK3CB, AKT1, ACTA2) in hepatocytes, raising concerns about VLCKD suitability for IHR patients. IHR sEVs also decreased expression of HDAC10, HDAC6, HDAC3, MMP19, and MMP2, while increasing modulation of p-AKT, α-SMA, and VIM. Conclusion. These findings underscore the critical role of sEVs in regulating inflammation, remodeling, and hepatic stress responses, particularly in IHR patients, and suggest sEVs could complement instrumental evaluations like FibroScan in fibrosis assessment.
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Affiliation(s)
- Francesco Balestra
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Maria De Luca
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Giorgia Panzetta
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Nicoletta Depalo
- Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Bari Research Unit, Via Orabona 4, 70126 Bari, Italy
| | - Federica Rizzi
- Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Bari Research Unit, Via Orabona 4, 70126 Bari, Italy
| | - Rita Mastrogiacomo
- Department of Chemistry, University of Bari, Via Orabona 4, 70125 Bari, Italy
| | - Sergio Coletta
- Core Facility Biobank, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Grazia Serino
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Emanuele Piccinno
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Dolores Stabile
- Core Facility Biobank, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Pasqua Letizia Pesole
- Core Facility Biobank, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Valentina De Nunzio
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Giuliano Pinto
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Nicole Cerabino
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Martina Di Chito
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Maria Notarnicola
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Endrit Shahini
- Gastroenterology Unit, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Giovanni De Pergola
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
| | - Maria Principia Scavo
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy
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Kurbatova IV, Topchieva LV, Dudanova OP, Shipovskaya AA. Role of MMP-2 and MMP-9 in the Relationship between Inflammation, Fibrosis, and Apoptosis during Progression of Non-Alcoholic Fatty Liver Disease and Diagnostic Significance of Plasma Levels of Their Active Forms. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:1998-2022. [PMID: 39647828 DOI: 10.1134/s0006297924110130] [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: 04/02/2024] [Revised: 10/14/2024] [Accepted: 10/15/2024] [Indexed: 12/10/2024]
Abstract
MMP-2 and MMP-9 play an important role in pathogenesis of chronic liver diseases, participating in the processes of inflammation and fibrosis. Their role in progression of non-alcoholic fatty liver disease (NAFLD) is poorly understood. Analysis of MMP-2, -9 levels in the blood plasma of patients with different forms of NAFLD [liver steatosis (LS) and non-alcoholic steatohepatitis (NASH) of weak (-WA), moderate (MA), high (-HA) activity without pronounced fibrosis] was performed. Correlations between the levels of MMP-2, -9 and mRNA of the genes MMP2, MMP9, ADAM17, NLRP3, caspase 3 activity in peripheral blood leukocytes (PBL), TNFα, IL-6, sIL-6R, cytokeratin-18 fragments in plasma were assessed. In steatosis, the levels of MMP2 gene mRNA in PBL and MMP-2 in plasma are lower than in the control, and expression of the NLRP3 gene in PBL is increased relative to other groups. In the NASH-WA, the level of MMP-9 is higher than in the control, in LS, and in NASH-MA, which could be associated with activation of inflammation during transformation of LS into NASH. The plasma level of MMP-9 over 389.50 pg/ml has been shown to be diagnostically significant for identification of NASH-WA among the patients with steatosis (AUC ROC = 0.818, 95% CI = 0.689-0.948, p < 0.001). In NAFLD, the level of MMP-9 could be associated not only with inflammation, but also with apoptosis. ADAM17 probably plays a certain role in this regard. In the advanced NASH, hepatocyte apoptosis is increased, the level of caspase 3 activity in PBL is increased, the level of MMP-9 in the blood is reduced to the level of the control and LS. In the NASH-HA, the level of mRNA of the ADAM17 gene in PBL is increased compared to the control, NASH-WA, and NASH-MA. Thus, MMP-2 and MMP-9 are involved in pathogenesis of NAFLD already at the early stages and their level in blood could be associated with the presence and severity of inflammation in the liver parenchyma.
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Affiliation(s)
- Irina V Kurbatova
- Institute of Biology, Karelian Research Centre, Russian Academy of Sciences, Petrozavodsk, Karelia, 185910, Russia.
| | - Lyudmila V Topchieva
- Institute of Biology, Karelian Research Centre, Russian Academy of Sciences, Petrozavodsk, Karelia, 185910, Russia
| | - Olga P Dudanova
- Zilber Medical Institute, Petrozavodsk State University, Petrozavodsk, Karelia, 185910, Russia
| | - Anastasia A Shipovskaya
- Zilber Medical Institute, Petrozavodsk State University, Petrozavodsk, Karelia, 185910, Russia
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Shigehara K, Kato Y, Shinzawa R, Konaka H, Kawaguchi S, Nohara T, Izumi K, Namiki M, Mizokami A. Testosterone Replacement Therapy Can Improve a Biomarker of Liver Fibrosis in Hypogonadal Men: A Subanalysis of a Prospective Randomized Controlled Study in Japan (EARTH Study). World J Mens Health 2024; 42:42.e89. [PMID: 39434391 DOI: 10.5534/wjmh.240066] [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: 03/16/2024] [Revised: 06/28/2024] [Accepted: 07/15/2024] [Indexed: 10/23/2024] Open
Abstract
PURPOSE We investigated the effects of testosterone replacement therapy (TRT) on the Fibrosis-4 (FIB-4) index among hypogonadal patients who were extracted from a randomized controlled study in Japan (the EARTH study). MATERIALS AND METHODS Data of 186 patients (88 in the TRT group; 98 in the control group) were collected. The patients in the TRT group received intramuscular administration of testosterone enanthate (250 mg) every 4 weeks for 12 months. The patients' background information such as current medical history and lifestyle habits were collected. Waist circumference, body mass index, and body fat volume were measured at baseline and 12-month visit. Fasting blood sugar (FBS), hemoglobin A1c, total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol levels were collected at baseline and 12-month visit. The FIB-4 index was calculated according to age, aspartate aminotransferase, alanine transaminase, and platelet count. RESULTS Except for serum FBS values, most of baseline characteristics were comparable between the TRT and control groups. When comparing the changes of each variable from baseline at 12-month visit in both groups, significant differences were found in waist circumference (p=0.00248), fat volume (p=0.00812), and platelet counts (p=0.0478), whereas a FIB-4 index did not change. On the contrary, in a subanalysis including only patients with a FIB-4 index ≥1.30 at baseline, a significant difference in a FIB-4 index (-0.10±0.39 vs. 0.04±0.44; p=0.0311) was observed with significant decreases in waist circumference, body fat volume, and TG levels, and an increase in platelet counts. The FIB-4 index was significantly decreased by TRT from 1.98±0.52 to 1.87±0.60 (p=0.0277). CONCLUSIONS TRT for 12 months improved the FIB-4 index among hypogonadal men with a higher baseline FIB-4 index.
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Affiliation(s)
- Kazuyoshi Shigehara
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
| | - Yuki Kato
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Rei Shinzawa
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Hiroyuki Konaka
- Department of Urology, Kanazawa Red Cross Hospital, Kanazawa, Japan
| | - Shohei Kawaguchi
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Takahiro Nohara
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kouji Izumi
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Mikio Namiki
- Department of Urology, Hasegawa Hospital, Toyama, Japan
| | - Atsushi Mizokami
- Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
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9
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Lan Y, Guo Z, Dai J, Chen K, Chen Y. Association between remnant cholesterol and metabolic dysfunction-associated steatotic liver disease in the elderly. Dig Liver Dis 2024; 56:1557-1564. [PMID: 38582712 DOI: 10.1016/j.dld.2024.03.013] [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: 12/09/2023] [Revised: 02/23/2024] [Accepted: 03/18/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND & AIMS Whether maintaining optimal remnant cholesterol (RC) levels later in life may improve metabolic dysfunction-associated steatotic liver disease (MASLD) outcomes remained ambiguous. This study aimed to investigate the relationship between RC and MASLD in the elderly Chinese population. METHODS A total of 131,868 subjects aged ≥ 65 years were included in this study. The association of RC with MASLD, and severity of MASLD was analyzed by logistic regression. In addition, stratified analysis was conducted to test the potential interaction. RESULTS MASLD prevalence and RC concentration decreased with age. After adjustment for possible confounders, the odds ratio of MASLD at the highest quartile of RC compared to the lowest quartile was 1.587(95% CI: 1.524-1.652), and this effect remained in MASLD with liver fibrosis. Stratified analysis showed a more prominent effect on the MASLD in males, those aged 65-69 years, those without central obesity, those with diabetes, and normal level of total cholesterol, low-density lipoprotein cholesterol (Pfor interaction<0.05). CONCLUSIONS In the elderly subset of the Chinese population, higher RC levels achieved a significant risk effect against MASLD. More RC monitoring should be given to older for the prevention and intervention of MASLD.
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Affiliation(s)
- Yanqi Lan
- Xiamen Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Zhinan Guo
- Xiamen Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Junsheng Dai
- Xiamen Municipal Health Commission, Xiamen, Fujian, China
| | - Kailin Chen
- Xiamen Municipal Health Commission, Xiamen, Fujian, China
| | - Youlan Chen
- Xiamen Center for Disease Control and Prevention, Xiamen, Fujian, China.
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10
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Xuan Y, Hu W, Wang Y, Li J, Yang L, Yu S, Zhou D. Association between RC/HDL-C ratio and risk of non-alcoholic fatty liver disease in the United States. Front Med (Lausanne) 2024; 11:1427138. [PMID: 39135721 PMCID: PMC11317378 DOI: 10.3389/fmed.2024.1427138] [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: 05/03/2024] [Accepted: 07/16/2024] [Indexed: 08/15/2024] Open
Abstract
Background The occurrence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. The link between serum remnant cholesterol (RC) to high-density lipoprotein cholesterol (HDL-C) ratio and NAFLD remains unclear. Therefore, we sought to clarify the relationship between the RC/HDL-C ratio and the NAFLD. Methods Data for our cross-sectional study came from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) with 2,269 participants. Associations between RC/HDL-C levels and the prevalence of NAFLD and hepatic fibrosis were evaluated using adjusted multivariate logistic regression analyses. A generalized additive model examined the non-linear relationship between RC/HDL-C and the probability of developing NAFLD. Results Among 2,269 participants, 893 (39.36%) were diagnosed with NAFLD. In each of the three models, RC/HDL-C and NAFLD had a strong positive statistical relationship: model 1 (OR = 9.294, 95%CI: 6.785, 12.731), model 2 (OR = 7.450, 95%CI: 5.401, 10.278), and model 3 (OR = 2.734, 95%CI: 1.895, 3.944). In addition, the subgroup analysis by gender and BMI suggested that RC/HDL-C showed a positive correlation with NAFLD. The RC/HDL-C ratio was positively correlated with the degree of liver steatosis. There was an inverted U-shaped connection between the prevalence of NAFLD and RC/HDL-C, with an inflection point of 0.619 for all participants and 0.690 for men. Receiver operating characteristic (ROC) analysis showed that the predictive value of RC/HDL-C for NAFLD (area under the curve: 0.7139; 95%CI: 0.6923, 0.7354; P < 0.001), was better than traditional lipid parameters. Conclusion Increased RC/HDL-C levels are independently associated with an increased risk of NAFLD and the severity of liver steatosis in the American population. In addition, the RC/HDL-C ratio can be used as a simple and effective non-invasive biomarker to identify individuals with a high risk of NAFLD.
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Affiliation(s)
- Yanyan Xuan
- Department of Hospital Infection, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Hepatology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Weike Hu
- Department of Emergency, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Yudan Wang
- Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Jingwen Li
- Department of Hepatology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Lisha Yang
- Department of Hepatology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Songping Yu
- Department of Geriatrics Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Dongdong Zhou
- Department of General Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
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11
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Zhou H, Tian L, Wu Y, Liu S. Computed tomography-measured body composition can predict long-term outcomes for stage I-III colorectal cancer patients. Front Oncol 2024; 14:1420917. [PMID: 39040454 PMCID: PMC11260682 DOI: 10.3389/fonc.2024.1420917] [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: 04/21/2024] [Accepted: 06/20/2024] [Indexed: 07/24/2024] Open
Abstract
Background There remains a pressing need to identify biomarkers capable of reliably predicting prognostic outcomes for colorectal cancer (CRC) patients. As several body composition parameters have recently been reported to exhibit varying levels of prognostic significance in particular cancers, the present study was devised to assess the ability of body composition to predict long-term outcomes for CRC patients with different stages of disease. Methods In total, this retrospective analysis enrolled 327 stage I-III CRC patients whose medical records were accessed for baseline demographic and clinical data. Primary outcomes for these patients included disease-free and overall survival (DFS and OS). The prognostic performance of different musculature, visceral, and subcutaneous fat measurements from preoperative computed tomography (CT) scans was assessed. Results Over the course of follow-up, 93 of the enrolled patients experienced recurrent disease and 39 died. Through multivariate Cox regression analyses, the visceral/subcutaneous fat area (V/S) ratio was found to be independently associated with patient DFS (HR=1.93, 95% CI: 1.24-3.01, P=0.004), and the skeletal muscle index (SMI) as an independent predictor for OS (HR=0.43, 95% CI: 0.21-0.89, P=0.023). Through subgroup analyses, higher V/S ratios were found to be correlated with reduced DFS among patients with stage T3/4 (P=0.011), lymph node metastasis-positive (P=0.002), and TNM stage III (P=0.002) disease, whereas a higher SMI was associated with better OS in all T stages (P=0.034, P=0.015), lymph node metastasis-positive cases (P=0.020), and in patients with TNM stage III disease (P=0.020). Conclusion Both the V/S ratio and SMI offer potential utility as clinical biomarkers associated with long-term CRC patient prognosis. A higher V/S ratio and a lower SMI are closely related to poorer outcomes in patients with more advanced disease.
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Affiliation(s)
| | | | | | - Sibin Liu
- Radiology Department, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, China
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Banerjee A, Das D, Mukherjee S, Maji BK. Comprehensive study of the interplay between immunological and metabolic factors in hepatic steatosis. Int Immunopharmacol 2024; 133:112091. [PMID: 38657500 DOI: 10.1016/j.intimp.2024.112091] [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: 02/17/2024] [Revised: 04/08/2024] [Accepted: 04/11/2024] [Indexed: 04/26/2024]
Abstract
The pathophysiology of hepatic steatosis is thoroughly reviewed in this comprehensive report, with particular attention to the complex interactions between inflammatory pathways, insulin resistance, lipid metabolism, metabolic dysregulation, and immunological responses in the liver including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). The study highlights the role of immune cell regulation in disease progression and explores the potential of immune cell-specific treatments for treating hepatic disorders. The development of liver disorders is significantly influenced by immune cells, including dendritic cells, T cells, and natural killer cells. Clinical investigations show that immune cell-specific treatments can effectively reduce liver fibrosis and inflammation. Future research should focus on finding new immunological targets for therapeutic interventions, as well as addressing the management challenges associated with NAFLD/NASH. Hepatic immune microorganisms also impact liver homeostasis and disorders. Improvements in immune cell regulation and liver transplantation methods give patients hope for better prognoses. Important phases include optimizing the selection of donors for malignancy of the liver, using machine perfusion for organ preservation, and fine-tuning immunosuppressive strategies. For focused treatments in hepatic steatosis, it is imperative to understand the intricate interactions between immune and metabolic variables. Understanding the liver's heterogeneous immune profile, encompassing a range of immune cell subpopulations, is crucial for formulating focused therapeutic interventions. To improve patient care and outcomes in hepatic illnesses, there is an urgent need for further research and innovation. Therefore, to effectively treat hepatic steatosis, it is important to enhance therapeutic techniques and maximize liver transplantation strategies.
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Affiliation(s)
- Arnab Banerjee
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly 712201, West Bengal, India.
| | - Debasmita Das
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly 712201, West Bengal, India
| | - Sandip Mukherjee
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly 712201, West Bengal, India
| | - Bithin Kumar Maji
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly 712201, West Bengal, India.
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Jiang L, Wang Q, Jiang Y, Peng D, Zong K, Li S, Xie W, Zhang C, Li K, Wu Z, Huang Z. Identification of diagnostic gene signatures and molecular mechanisms for non-alcoholic fatty liver disease and Alzheimer's disease through machine learning algorithms. Clin Chim Acta 2024; 557:117892. [PMID: 38537674 DOI: 10.1016/j.cca.2024.117892] [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: 02/19/2024] [Revised: 03/23/2024] [Accepted: 03/24/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and Alzheimer's disease (AD) pose significant global health challenges. Recent studies have suggested a link between these diseases; however, the underlying mechanisms remain unclear. This study aimed to decode the shared molecular landscapes of NAFLD and AD using bioinformatic approaches. METHODS We analyzed three datasets for NAFLD and AD from the Gene Expression Omnibus (GEO). This study involved identifying differentially expressed genes (DEGs), using weighted gene co-expression network analysis (WGCNA), and using machine learning for biomarker discovery. The diagnostic biomarkers were validated using expression analysis, receiver operating characteristic (ROC) curves, and nomogram models. Furthermore, Gene Set Enrichment Analysis (GSEA) and CIBERSORT were used to investigate molecular pathways and immune cell distributions related to GADD45G and NUPR1. RESULTS This study identified 14 genes that are common to NAFLD and AD. Machine learning identified six biomarkers for NAFLD, four for AD, and two crucial shared biomarkers: GADD45G and NUPR1. Validation confirmed their expression patterns and robust predictive abilities. GSEA revealed the intricate roles of these biomarkers in disease-associated pathways. Immune cell profiling highlighted the importance of macrophages under these conditions. CONCLUSION This study highlights GADD45G and NUPR1 as key biomarkers for NAFLD and AD, and provides novel insights into their molecular connections. These findings revealed potential therapeutic targets, particularly in macrophage-mediated pathways, thus enriching our understanding of these complex diseases.
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Affiliation(s)
- Liqing Jiang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qian Wang
- Department of General Practice, Chengdu Seventh People's Hospital, Chengdu, China
| | - Yingsong Jiang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dadi Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kezhen Zong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shan Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Wenyuan Xie
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Cheng Zhang
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Kaili Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Zhongjun Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
| | - Zuotian Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
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Choi H, Hong J, Seo Y, Joo SH, Lim H, Lahiji SF, Kim YH. Self-Assembled Oligopeptoplex-Loaded Dissolving Microneedles for Adipocyte-Targeted Anti-Obesity Gene Therapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2309920. [PMID: 38213134 DOI: 10.1002/adma.202309920] [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: 09/25/2023] [Revised: 12/16/2023] [Indexed: 01/13/2024]
Abstract
Advancements in gene delivery systems are pivotal for gene-based therapeutics in oncological, inflammatory, and infectious diseases. This study delineates the design of a self-assembled oligopeptoplex (SA-OP) optimized for shRNA delivery to adipocytes, targeting obesity and associated metabolic syndromes. Conventional systems face challenges, including instability due to electrostatic interactions between genetic materials and cationic oligopeptides. Additionally, repeated injections induce discomfort and compromise patient well-being. To circumvent these issues, a dissolvable hyaluronic acid-based, self-locking microneedle (LMN) patch is developed, with improved micro-dose efficiency, for precise SA-OP delivery. This platform offers pain-free administration and improved SA-OP storage stability. In vitro studies in 3T3-L1 cells demonstrated improvements in SA-OP preservation and gene silencing efficacy. In vivo evaluation in a mice model of diet-induced type 2 diabetes yielded significant gene silencing in adipose tissue and a 21.92 ± 2.51% reduction in body weight with minimum relapse risk at 6-weeks post-treatment, representing a superior therapeutic efficacy in a truncated timeframe relative to the GLP-1 analogues currently available on the market. Additionally, SA-OP (LMN) mitigated insulin resistance, inflammation, and hepatic steatosis. These findings establish SA-OP (LMN) as a robust, minimally invasive transdermal gene delivery platform with prolonged storage stability for treating obesity and its metabolic comorbidities.
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Affiliation(s)
- Heekyung Choi
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Juhyeong Hong
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Yuha Seo
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Seung-Hwan Joo
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Hanseok Lim
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Shayan Fakhraei Lahiji
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Cursus Bio Inc., Icure Tower, Seoul, 06170, Republic of Korea
| | - Yong-Hee Kim
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea
- Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
- Cursus Bio Inc., Icure Tower, Seoul, 06170, Republic of Korea
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Sila A, De Nucci S, Bonfiglio C, Di Stasi V, Cerabino N, Di Chito M, Rinaldi R, Cantalice P, Shahini E, Giannuzzi V, Pesole PL, Coletta S, Tutino NM, Piazzolla G, Cozzolongo R, Giannelli G, De Pergola G. Higher-Level Steatosis Is Associated with a Greater Decrease in Metabolic Dysfunction-Associated Steatoic Liver Disease after Eight Weeks of a Very Low-Calorie Ketogenic Diet (VLCKD) in Subjects Affected by Overweight and Obesity. Nutrients 2024; 16:874. [PMID: 38542785 PMCID: PMC10975408 DOI: 10.3390/nu16060874] [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: 02/20/2024] [Revised: 03/09/2024] [Accepted: 03/15/2024] [Indexed: 10/06/2024] Open
Abstract
The most common form of chronic liver disease, recently defined as MASLD, is strongly linked to obesity and metabolic syndrome. Lifestyle changes are part of MASLD prevention. The very low-calorie ketogenic diet (VLCKD) is a useful option for treating MASLD and reducing liver steatosis in patients with obesity. We assessed whether a greater degree of steatosis could have a positive or negative impact on how well 8 weeks of using the VLCKD improve steatosis and fibrosis in a patient population of overweight and obese individuals. Anthropometric parameters, along with changes in hormone and metabolic biomarkers, were also assessed both before and after the dietary change. The study population included 111 overweight (14.41%) or obese subjects (85.59%) aged between 18 and 64 years; the 75 women and 36 men involved were not taking any medicine. In both the raw (0.37 95% CI 0.21; 0.52) and the multivariate models (model a: 0.439 95% CI 0.26; 0.62; model b: 0.437 95% CI 0.25; 0.63), there was a positive and statistically significant correlation between the CAP delta value and the CAP before using the VLCKD. Additionally, the liver stiffness delta was found to be positively and statistically significantly correlated with liver stiffness before the use of the VLCKD in both models: the multivariate model (model a: 0.560 95% CI 0.40; 0.71; model b: 0.498 95% CI 0.34; 0.65) and the raw model (0.52 95% CI 0.39; 0.65). Systolic and diastolic blood pressure, insulin resistance (measured by HOMA-IR), insulin, HbA1c, fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, BMI, waist circumference, and fat mass, were all decreased (p < 0.001) following the use of the VLCKD. However, following the use of the VLCKD, there was an increase in vitamin D levels. (p < 0.001). We found that using the VLCKD for 8 weeks has a greater effect on improving steatosis and fibrosis in subjects who initially have more severe forms of these conditions.
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Affiliation(s)
- Annamaria Sila
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Sara De Nucci
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Caterina Bonfiglio
- Laboratory of Epidemiology and Statistics, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy;
| | - Vincenza Di Stasi
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Nicole Cerabino
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Martina Di Chito
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Roberta Rinaldi
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Paola Cantalice
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
| | - Endrit Shahini
- Department of Gastroenterology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy; (E.S.)
| | - Vito Giannuzzi
- Department of Gastroenterology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy; (E.S.)
| | - Pasqua Letizia Pesole
- Core Facility Biobank, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy (S.C.)
| | - Sergio Coletta
- Core Facility Biobank, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy (S.C.)
| | - Nicoletta Maria Tutino
- Laboratory of Clinical Pathology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy;
| | - Giuseppina Piazzolla
- Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Raffaele Cozzolongo
- Department of Gastroenterology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy; (E.S.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy;
| | - Giovanni De Pergola
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (A.S.); (S.D.N.); (V.D.S.); (R.R.)
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Tarantino G, Citro V. Could Adverse Effects of Antibiotics Due to Their Use/Misuse Be Linked to Some Mechanisms Related to Nonalcoholic Fatty Liver Disease? Int J Mol Sci 2024; 25:1993. [PMID: 38396671 PMCID: PMC10888279 DOI: 10.3390/ijms25041993] [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: 01/12/2024] [Revised: 01/31/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Nonalcoholic fatty liver disease, recently re-named metabolic dysfunction-associated steatotic fatty liver disease, is considered the most prevalent liver disease worldwide. Its molecular initiation events are multiple and not always well-defined, comprising insulin resistance, chronic low-grade inflammation, gut dysbiosis, and mitochondrial dysfunction, all of them acting on genetic and epigenetic grounds. Nowadays, there is a growing public health threat, which is antibiotic excessive use and misuse. This widespread use of antibiotics not only in humans, but also in animals has led to the presence of residues in derived foods, such as milk and dairy products. Furthermore, antibiotics have been used for many decades to control certain bacterial diseases in high-value fruit and vegetables. Recently, it has been emphasised that antibiotic-induced changes in microbial composition reduce microbial diversity and alter the functional attributes of the microbiota. These antibiotic residues impact human gut flora, setting in motion a chain of events that leads straight to various metabolic alterations that can ultimately contribute to the onset and progression of NAFLD.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, Medical School of Naples, Federico II University, 80131 Naples, Italy
| | - Vincenzo Citro
- Department of General Medicine, Umberto I Hospital, Nocera Inferiore (SA), 84014 Nocera Inferiore, Italy;
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Greco F, Piccolo CL, D’Andrea V, Scardapane A, Beomonte Zobel B, Mallio CA. Fat Matters: Exploring Cancer Risk through the Lens of Computed Tomography and Visceral Adiposity. J Clin Med 2024; 13:453. [PMID: 38256587 PMCID: PMC10817009 DOI: 10.3390/jcm13020453] [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: 12/16/2023] [Revised: 01/08/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Obesity is an established risk factor for cancer. However, conventional measures like body mass index lack precision in assessing specific tissue quantities, particularly of the two primary abdominal fat compartments, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Computed tomography (CT) stands as the gold standard for precisely quantifying diverse tissue types. VAT, distinguished by heightened hormonal and metabolic activity, plays a pivotal role in obesity-related tumor development. Excessive VAT is linked to aberrant secretion of adipokines, proinflammatory cytokines, and growth factors, fostering the carcinogenesis of obesity-related tumors. Accurate quantification of abdominal fat compartments is crucial for understanding VAT as an oncological risk factor. The purpose of the present research is to elucidate the role of CT, performed for staging purposes, in assessing VAT (quantity and distribution) as a critical factor in the oncogenesis of obesity-related tumors. In the field of precision medicine, this work takes on considerable importance, as quantifying VAT in oncological patients becomes fundamental in understanding the influence of VAT on cancer development-the potential "phenotypic expression" of excessive VAT accumulation. Previous studies analyzed in this research showed that VAT is a risk factor for clear cell renal cell carcinoma, non-clear cell renal cell carcinoma, prostate cancer, and hepatocarcinoma recurrence. Further studies will need to quantify VAT in other oncological diseases with specific mutations or gene expressions, in order to investigate the relationship of VAT with tumor genomics.
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Affiliation(s)
- Federico Greco
- Department of Radiology, Cittadella della Salute Azienda Sanitaria Locale di Lecce, Piazza Filippo Bottazzi 2, 73100 Lecce, Italy
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
| | - Claudia Lucia Piccolo
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Valerio D’Andrea
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Arnaldo Scardapane
- Dipartimento Interdisciplinare di Medicina, Sezione di Diagnostica per Immagini, Università degli Studi di Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Bruno Beomonte Zobel
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Carlo Augusto Mallio
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
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18
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Liu L, Wang C, Hu Z, Deng S, Yang S, Zhu X, Deng Y, Wang Y. Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study. Environ Health Prev Med 2024; 29:5. [PMID: 38325840 PMCID: PMC10853394 DOI: 10.1265/ehpm.23-00289] [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: 10/10/2023] [Accepted: 12/30/2023] [Indexed: 02/09/2024] Open
Abstract
BACKGROUND AND AIM Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
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Affiliation(s)
- Lei Liu
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Changfa Wang
- General Surgery Department, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Zhongyang Hu
- Department of Neurology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Shuwen Deng
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Saiqi Yang
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Xiaoling Zhu
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Yuling Deng
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
| | - Yaqin Wang
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, China, 410013
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Cheng Y, Chen W, Xu J, Liu H, Chen T, Hu J. Genetic analysis of potential biomarkers and therapeutic targets in age-related hearing loss. Hear Res 2023; 439:108894. [PMID: 37844444 DOI: 10.1016/j.heares.2023.108894] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 09/06/2023] [Accepted: 09/27/2023] [Indexed: 10/18/2023]
Abstract
Age-related hearing loss (ARHL) or presbycusis is the phenomenon of hearing loss due to the aging of auditory organs with age. It seriously affects the cognitive function and quality of life of the elderly. This study is based on comprehensive bioinformatic and machine learning methods to identify the critical genes of ARHL and explore its therapy targets and pathological mechanisms. The ARHL and normal samples were from GSE49543 datasets of the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to obtain significant modules. The Limma R-package was used to identify differentially expressed genes (DEGs). The 15 common genes of the practical module and DEGs were screened. Functional enrichment analysis suggested that these genes were mainly associated with inflammation, immune response, and infection. Cytoscape software created the protein-protein interaction (PPI) layouts and cytoHubba, support vector machine-recursive feature elimination (SVM-RFE), and random forests (RF) algorithms screened hub genes. After validating the hub gene expressions in GSE6045 and GSE154833 datasets, Clec4n, Mpeg1, and Fcgr3 are highly expressed in ARHL and have higher diagnostic efficacy for ARHL, so they were identified as hub genes. In conclusion, Clec4n, Mpeg1, and Fcgr3 play essential roles in developing ARHL, and they might become vital targets in ARHL diagnosis and anti-inflammatory therapy.
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Affiliation(s)
- Yajing Cheng
- Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Wenjin Chen
- Department of Neurosurgery, Peking University Shenzhen Hospital, Shenzhen, China
| | - Jia Xu
- Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Hang Liu
- Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Ting Chen
- Department of Neurology, Shenzhen Second People's Hospital, Shenzhen, China
| | - Jun Hu
- Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
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20
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De Nucci S, Bonfiglio C, Donvito R, Di Chito M, Cerabino N, Rinaldi R, Sila A, Shahini E, Giannuzzi V, Pesole PL, Coletta S, Lanzilotta E, Piazzolla G, Cozzolongo R, Giannelli G, De Pergola G. Effects of an Eight Week Very Low-Calorie Ketogenic Diet (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with Overweight and Obesity. Nutrients 2023; 15:4468. [PMID: 37892542 PMCID: PMC10610501 DOI: 10.3390/nu15204468] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023] Open
Abstract
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are frequently associated conditions characterized by low-grade inflammation. Very low-calorie ketogenic diet (VLCKD) strategies are commonly used to simultaneously obtain weight loss and an improvement of liver steatosis. We evaluated the efficacy of 8 weeks' VLCKD in decreasing the white blood cell (WBC) and platelet (PLT) counts, as well as liver steatosis and fibrosis, diagnosed using transient elastography (FibroScan). Metabolic and anthropometric parameters commonly associated with MASLD were also evaluated. This study included 87 participants; 58 women and 29 men aged between 18 and 64 years with overweight (18%) or obesity (82%), but not taking any medication. Anthropometric measurements, bioimpedance analysis, and biochemical assays were performed before and after the dietary intervention. BMI (kg/m2) (p-value < 0.001), waist circumference (cm) (p-value < 0.001), and fat mass (kg) (p-value < 0.001) were significantly decreased following VLCKD. After VLCKD, the FibroScan parameter CAP (db/m), which measures the accumulation of fatty liver, significantly decreased (p-value < 0.001), as did liver stiffness (kPA), the FibroScan parameter quantifying liver fibrosis (p-value < 0.05). Seemingly, WBC (p-value < 0.001) and PLT (p-value < 0.001) counts were lowered by VLCKD in the whole group; however, the decrease in WBC and platelet counts were significant only in patients with steatosis (CAP ≥ 215 dB/m). Fasting blood glucose (p-value < 0.001), insulin (p-value < 0.001), HbA1c (p-value < 0.001), triglycerides (p-value < 0.001), total cholesterol (p-value < 0.001), LDL-cholesterol (p-value < 0.001), HDL-cholesterol (p-value < 0.001); γGT (p-value < 0.001) blood levels and insulin resistance (as measured by HOMAIR) (p-value < 0.001); and systolic (p-value < 0.001), and diastolic (p-value < 0.001) blood pressure levels, were all significantly lower after VLCKD. In contrast, blood levels of vitamin D were higher following the diet (p-value < 0.001). We conclude that treating subjects with overweight and obesity with VLCKD is followed by a simultaneous reduction in WBCs and platelets, the expression of low-grade inflammation, and of liver steatosis and fibrosis. Therefore, we can hypothesize that VLCKD decreases general and liver low-grade inflammation, thus improving liver health.
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Affiliation(s)
- Sara De Nucci
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
| | - Caterina Bonfiglio
- Laboratory of Epidemiology and Statistics, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy
| | - Rosanna Donvito
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
| | - Martina Di Chito
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
| | - Nicole Cerabino
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
| | - Roberta Rinaldi
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
| | - Annamaria Sila
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
| | - Endrit Shahini
- Department of Gastroenterology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy; (E.S.)
| | - Vito Giannuzzi
- Department of Gastroenterology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy; (E.S.)
| | - Pasqua Letizia Pesole
- Core Facility Biobank, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy
| | - Sergio Coletta
- Core Facility Biobank, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy
| | - Elsa Lanzilotta
- Laboratory of Clinical Pathology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy
| | - Giuseppina Piazzolla
- Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Raffaele Cozzolongo
- Department of Gastroenterology, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy; (E.S.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology “Saverio de Bellis”, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy;
| | - Giovanni De Pergola
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy (R.R.)
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21
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Grander C, Grabherr F, Tilg H. Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options. Cardiovasc Res 2023; 119:1787-1798. [PMID: 37364164 PMCID: PMC10405569 DOI: 10.1093/cvr/cvad095] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/30/2022] [Accepted: 06/23/2023] [Indexed: 06/28/2023] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic disease accompanied frequently by insulin resistance and hepatic and systemic inflammation. Whereas simple hepatic steatosis is the most common disease manifestation, a more progressive disease course characterized by liver fibrosis and inflammation (i.e. non-alcoholic steatohepatitis) is present in 10-20% of affected individuals. NAFLD furthermore progresses in a substantial number of patients towards liver cirrhosis and hepatocellular carcinoma. Whereas this disease now affects almost 25% of the world's population and is mainly observed in obesity and type 2 diabetes, NAFLD also affects lean individuals. Pathophysiology involves lipotoxicity, hepatic immune disturbances accompanied by hepatic insulin resistance, a gut dysbiosis, and commonly hepatic and systemic insulin resistance defining this disorder a prototypic systemic metabolic disorder. Not surprisingly many affected patients have other disease manifestations, and indeed cardiovascular disease, chronic kidney disease, and extrahepatic malignancies are all contributing substantially to patient outcome. Weight loss and lifestyle change reflect the cornerstone of treatment, and several medical treatment options are currently under investigation. The most promising treatment strategies include glucagon-like peptide 1 receptor antagonists, sodium-glucose transporter 2 inhibitors, Fibroblast Growth Factor analogues, Farnesoid X receptor agonists, and peroxisome proliferator-activated receptor agonists. Here, we review epidemiology, pathophysiology, and therapeutic options for NAFLD.
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Affiliation(s)
- Christoph Grander
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria
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22
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Ng JJJ, Loo WM, Siah KTH. Associations between irritable bowel syndrome and non-alcoholic fatty liver disease: A systematic review. World J Hepatol 2023; 15:925-938. [PMID: 37547029 PMCID: PMC10401413 DOI: 10.4254/wjh.v15.i7.925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 06/12/2023] [Accepted: 07/03/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is associated with obesity and metabolic syndrome. IBS and non-alcoholic fatty liver disease (NAFLD) are highly prevalent entities worldwide and may share similar mechanisms including gut dysbiosis, impaired intestinal mucosal barrier and immune system activation.
AIM To systematically review their association according to the Preferred Reporting Items for Systemic Review and Meta-analyses guidelines.
METHODS PubMed, EMBASE and Cochrane Database of Systematic Reviews were searched for relevant papers. Manual searches were also performed.
RESULTS Six studies were included. Both IBS and NAFLD subjects had significantly more metabolic risk factors like hypertension, obesity, dyslipidaemia and diabetes. Our review showed that 23.2% to 29.4% of NAFLD patients had IBS. IBS was significantly higher in NAFLD patients compared with patients without NAFLD (23.2% vs 12.5%, P < 0.01). A higher proportion of IBS patients had NAFLD (65.8% to 74.0%). IBS patients were three times more likely to have NAFLD compared with non-IBS patients (P < 0.001). Two studies showed a significant correlation between the severity of IBS and NAFLD. The proportion of NAFLD subjects with IBS increased with NAFLD severity.
CONCLUSION Further prospective studies are warranted to evaluate the relationship and shared pathways between IBS and NAFLD, potentially leading to the development of future therapeutics.
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Affiliation(s)
- Jareth Jun Jie Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Wai Mun Loo
- AliveoMedical, Mount Alvernia and Mount Elizabeth Hospitals, Singapore 574623, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore 119228, Singapore
- Department of Medicine, National University Hospital, Singapore 119228, Singapore
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23
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Badali T, Arefhosseini S, Rooholahzadegan F, Tutunchi H, Ebrahimi-Mameghani M. The effect of DASH diet on atherogenic indices, pro-oxidant-antioxidant balance, and liver steatosis in obese adults with non-alcoholic fatty liver disease: A double-blind controlled randomized clinical trial. Health Promot Perspect 2023; 13:77-87. [PMID: 37309438 PMCID: PMC10257571 DOI: 10.34172/hpp.2023.10] [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: 10/13/2022] [Accepted: 01/24/2023] [Indexed: 06/14/2023] Open
Abstract
Background: The present clinical trial aimed to examine whether adherence to Dietary Approaches to Stop Hypertension (DASH) diet could improve lipid profile, the Pro-oxidant-antioxidant balance (PAB) as well as liver function in obese adults with non-alcoholic fatty liver disease (NAFLD). Methods: Sixty two patients with NAFLD were equally allocated into either DASH or low-calorie diet (LCD) group for 8 weeks. The primary and secondary outcomes were determined before and after the trial. Results: Forty patients completed the trial. Significant within group differences were found in dietary saturated fat, selenium, vitamins A and E as well as body weight and body mass index (BMI) and waist circumference (WC) after the intervention (P<0.05). DASH diet showed greater significant change in systolic and diastolic blood pressure without significant differences between the groups after 8 weeks. Apart from serum high-density lipoprotein cholesterol (HDL-C) and triglyceride/HDL-C, greater reductions were found not only in serum lipids and atherogenic indices (P<0.05) but also in serum aspartate aminotransferase (AST), AST to platelet ratio index (APRI) and lipid accumulation product (LAP) in DASH group in comparison to control group (P=0.008, P=0.019 and P=0.003, respectively). Nevertheless, there was not any difference in PAB level between the groups. Furthermore, adherence to DASH diet was more effective in alleviating liver steatosis compared with usual LCD (P=0.012). Conclusion: Adherence to DASH diet appears to be more effective in improving obesity, atherogenic and liver steatosis biomarkers but not oxidative stress (OS) than usual LCD.
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Affiliation(s)
- Taghi Badali
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Arefhosseini
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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24
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Mansour A, Motamed S, Hekmatdoost A, Karimi S, Mohajeri-Tehrani MR, Abdollahi M, Jelodar R, Sajjadi-Jazi SM. Factors related to hypermetabolism in individuals with type 2 diabetes mellitus and non-alcoholic fatty liver disease. Sci Rep 2023; 13:3669. [PMID: 36871124 PMCID: PMC9985614 DOI: 10.1038/s41598-023-30945-w] [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: 11/16/2022] [Accepted: 03/03/2023] [Indexed: 03/06/2023] Open
Abstract
Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80-33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p < 0.05). According to the results of multivariable logistic regression analyses, hypermetabolism had a positive association with adiponectin (odds ratio [OR] 1.167, 95% confidence interval [CI] 1.015-1.342, p = 0.030), physical activity (OR 1.134, 95% CI 1.002-1.284, p = 0.046), alanine transaminase (OR 1.062, 95% CI 1.006-1.122, p = 0.031) and diastolic blood pressure (OR 1.067, 95% CI 1.010-1.127, p = 0.021). However, fat free mass was inversely related to hypermetabolism (OR 0.935, 95% CI 0.883-0.991, p = 0.023). Adiponectin, alanine transaminase, physical activity, diastolic blood pressure and fat free mass were independently associated with hypermetabolism in subjects with NAFLD and T2DM.
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Affiliation(s)
- Asieh Mansour
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Azita Hekmatdoost
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Karimi
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Mohajeri-Tehrani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reihane Jelodar
- Department of Internal Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Sayed Mahmoud Sajjadi-Jazi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Gulzar F, Ahmad S, Singh S, Kumar P, Sharma A, Tamrakar AK. NOD1 activation in 3T3-L1 adipocytes confers lipid accumulation in HepG2 cells. Life Sci 2023; 316:121400. [PMID: 36657640 DOI: 10.1016/j.lfs.2023.121400] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/04/2023] [Accepted: 01/12/2023] [Indexed: 01/17/2023]
Abstract
AIMS Activation of specific innate immune receptors has been characterized to modulate nutrient metabolism in individual metabolic tissue directly or indirectly via secretory molecules. Activation of the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in adipocytes has been reported to induce lipolysis linked with insulin resistance and inflammatory response. These cues are positioned to modulate metabolic action in distal organs through paracrine/endocrine signaling. Here, we assessed the role of NOD1-mediated lipolysis and inflammatory response in adipocytes to affect lipid metabolism in hepatocytes. MAIN METHODS Human hepatoma cells (HepG2) were exposed to conditioned medium obtained from 3 T3-L1 adipocytes pretreated with NOD1 ligand (iE-DAP) and the effects on lipid accumulation, inflammation and insulin response were assessed. Activation of mechanisms leading to hepatic lipid accumulation was investigated by gene expression analysis. KEY FINDINGS The conditioned medium from NOD1-activated 3 T3-L1 adipocytes (CM-DAP) induced lipid accumulation in HepG2 cells, driven by both lipolysis and inflammatory responses. The CM-DAP-induced lipid accumulation was independent to de novo lipogenesis and resulted from the enhanced transport of fatty acids inside and consequent increase in rate of triglycerides synthesis in hepatocytes. Moreover, CM-DAP-induced lipid accumulation instigated the expression of the markers of fatty acid oxidation and VLDL assembly for the export of triglycerides from hepatocyte. Furthermore, CM-DAP-induced lipid accumulation was associated with induction of inflammatory response and impairment of insulin signaling in HepG2 cells. SIGNIFICANCE Beyond showing liver-specific mechanisms to adipocytes-derived factors, our findings support the involvement of adipose tissue as a mediator in NOD1-mediated biological responses to modulate hepatic metabolism.
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Affiliation(s)
- Farah Gulzar
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India
| | - Shadab Ahmad
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Sushmita Singh
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Pawan Kumar
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Aditya Sharma
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India
| | - Akhilesh K Tamrakar
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India.
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Ji J, Wu L, Wei J, Wu J, Guo C. The Gut Microbiome and Ferroptosis in MAFLD. J Clin Transl Hepatol 2023; 11:174-187. [PMID: 36406312 PMCID: PMC9647110 DOI: 10.14218/jcth.2022.00136] [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] [Received: 03/21/2022] [Revised: 05/22/2022] [Accepted: 06/12/2022] [Indexed: 12/04/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and is proposed to replace the previous name, nonalcoholic fatty liver disease (NAFLD). Globally, MAFLD/NAFLD is the most common liver disease, with an incidence rate ranging from 6% to 35% in adult populations. The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance (IR), and the genetic susceptibility to acquired metabolic stress-associated liver injury. Similarly, the gut microbiota in MAFLD/NAFLD is being revaluated by scientists, as the gut and liver influence each other via the gut-liver axis. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD, and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD. This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis. It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.
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Affiliation(s)
- Jie Ji
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liwei Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jue Wei
- Department of Gastroenterology Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jianye Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Correspondence to: Chuanyong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, NO. 301, Middle Yanchang Road, Jing’an District, Shanghai 200072, China. ORCID: https://orcid.org/0000-0002-6527-4673. E-mail: ; Jianye Wu: Department of Gastroenterology, Putuo People’s Hospital, NO. 1291, Jiangning road, Putuo, Shanghai 200060, China. ORCID: https://orcid.org/0000-0003-2675-4241. E-mail:
| | - Chuanyong Guo
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Correspondence to: Chuanyong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, NO. 301, Middle Yanchang Road, Jing’an District, Shanghai 200072, China. ORCID: https://orcid.org/0000-0002-6527-4673. E-mail: ; Jianye Wu: Department of Gastroenterology, Putuo People’s Hospital, NO. 1291, Jiangning road, Putuo, Shanghai 200060, China. ORCID: https://orcid.org/0000-0003-2675-4241. E-mail:
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Rooholahzadegan F, Arefhosseini S, Tutunchi H, Badali T, Khoshbaten M, Ebrahimi-Mameghani M. The effect of DASH diet on glycemic response, meta-inflammation and serum LPS in obese patients with NAFLD: a double-blind controlled randomized clinical trial. Nutr Metab (Lond) 2023; 20:11. [PMID: 36788518 PMCID: PMC9926705 DOI: 10.1186/s12986-023-00733-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND As dietary approaches to stop hypertension (DASH) dietary pattern has been shown to be effective in hypertension and obesity, the present study investigated the effects of following DASH diet on glycemic, meta-inflammation, lipopolysaccharides (LPS) and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD). METHODS In this double-blind controlled randomized clinical trial, 40 obese patients with NAFLD were randomly allocated into either "DASH diet" (n = 20) or calorie-restricted diet as "Control" (n = 20) group for 8 weeks. Anthropometric measures, blood pressure, glycemic response, liver enzymes, toll-like reseptor-4 (TLR-4) and monocyte chemoattractant protein (MCP-1) and LPS as well as Dixon's DASH diet index were assessed at baseline and after 8 weeks. RESULTS After 8 weeks, although all obesity indices decreased significantly in both groups, the reduction in all anthropometric measures were significantly greater in DASH vs control group, after adjusting for baseline values and weight change. Fasting glucose level decreased in both group, however, no inter-group significant difference was found at the end of study. Nevertheless, serum levels of hemoglobin A1c (HbA1c), TLR-4, MCP-1 and LPS as well as aspartate aminotransferase (AST) decreased significantly in DASH group, after adjusting for baseline values and weight change (p < 0.001, p = 0.004, p = 0.027, p = 0.011, and p = 0.008, respectively). The estimated number needed to treats (NNTs) for one and two grade reductions in NAFLD severity following DASH diet were 2.5 and 6.67, respectively. CONCLUSION Adherence to DASH diet could significantly improve weight, glycemia, inflammation and liver function in obese patients with NAFLD.
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Affiliation(s)
- Farnaz Rooholahzadegan
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Arefhosseini
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Helda Tutunchi
- grid.412888.f0000 0001 2174 8913Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taghi Badali
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manuchehr Khoshbaten
- grid.412888.f0000 0001 2174 8913Department of Internal Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Arefhosseini S, Roshanravan N, Tutunchi H, Rostami S, Khoshbaten M, Ebrahimi-Mameghani M. Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease. Front Nutr 2023; 10:1092544. [PMID: 36824177 PMCID: PMC9941177 DOI: 10.3389/fnut.2023.1092544] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/17/2023] [Indexed: 02/10/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome is closely associated with type 2 diabetes mellitus. Myo-inositol (MI)-a 6-C sugar alcohol-with insulin-mimetic, anti-diabetic, lipid-lowering, and anti-inflammatory properties has exerted favorable effects on insulin resistance-related disorders and metabolic disease, while recent animal studies revealed its positive effects on liver function. This study aimed to investigate the effects of MI supplementation on cardiometabolic factors, anthropometric measures, and liver function in obese patients with NAFLD. Methods This double-blinded placebo-controlled randomized clinical trial was carried out on 48 obese patients with NAFLD who were randomly assigned to either MI (4g/day) or placebo (maltodextrin 4g/day) along with dietary recommendations for 8 weeks. Glycemic indices, lipid profile, liver enzymes anthropometric measures, and blood pressure were evaluated pre- and post-intervention. Dietary intakes were assessed using a 3-day 24 h recall and analyzed by Nutritionist IV software. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and beta-cell function (HOMA-B) was also estimated. Results Anthropometric measures decreased significantly in both groups, while the reduction in weight (p = 0.049) and systolic blood pressure (p = 0.006) in the MI group was significantly greater than in the placebo group after adjusting for baseline values and energy intake. Although energy and macronutrient intakes decreased significantly in both groups, between-group differences were not significant after adjusting for the potential confounders. MI supplementation led to a significant reduction in serum fasting insulin (p = 0.008) and HOMA-IR (p = 0.046). There were significant improvements in lipid profile, liver enzymes, and aspartate aminotransferase/alanine aminotransferase ratio as well as serum ferritin level in the MI group, compared to the placebo group at the endpoint. By MI supplementation for eight weeks, 1 in 3 patients reduced one- grade in the severity of NAFLD. Conclusion MI supplementation could significantly improve IR, lipid profile, and liver function in patients with NAFLD. Further clinical trials with larger sample sizes, longer duration, different MI doses, and other inositol derivatives are recommended.
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Affiliation(s)
- Sara Arefhosseini
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Roshanravan
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayyeh Rostami
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manuchehr Khoshbaten
- Department of Internal Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran,*Correspondence: Mehrangiz Ebrahimi-Mameghani ✉
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Lee T, Chung TH. Comparative analysis of the relationship between four hepatic steatosis indices and muscle mass. Sci Rep 2023; 13:1645. [PMID: 36717652 PMCID: PMC9886852 DOI: 10.1038/s41598-023-28751-5] [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: 04/19/2022] [Accepted: 01/24/2023] [Indexed: 01/31/2023] Open
Abstract
Several studies have attempted to validate the relationship between hepatic steatosis and sarcopenia. The crucial limitation is to establish the status of hepatic steatosis by costly or invasive methods. Therefore, several models predicting non-alcoholic fatty liver disease (NAFLD) have been developed but have exhibited heterogeneous results. In this study, we aimed to review and compare four representative models and analyze their relationship with the risk of low muscle mass. Korea National Health and Nutrition Examination Surveys from 2008 to 2011 were used to confirm our hypothesis. Dual-energy X-ray absorptiometry was used to measure the amount of skeletal muscle mass. We used four hepatic steatosis indices: hepatic steatosis index (HSI), Framingham steatosis index (FSI), liver fat score (LFS), and fatty liver index (FLI). Multivariate linear and logistic regressions were used to reveal the relationship between NAFLD and low skeletal muscle index (LSMI). Pairs of FSI-FLI and HSI-FLI exhibited the best and second-best correlations among all possible pairs. The four hepatic steatosis models were associated with increased risk for LSMI. After removing the body mass index effect, HSI and FLI remained robust predictors for LSMI. NAFLD was a significant and potent risk factor for low skeletal muscle.
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Affiliation(s)
- Taesic Lee
- Department of Family Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, Republic of Korea.,The Study of Obesity and Metabolic Syndrome, Korean Academy of Family Medicine, Wonju, Republic of Korea
| | - Tae-Ha Chung
- Department of Family Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, Republic of Korea. .,Research Group of Functional Medicine and Preclinical Disease, Wonju, Republic of Korea.
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Effects of anti-inflammatory dietary patterns on non-alcoholic fatty liver disease: a systematic literature review. Eur J Nutr 2023; 62:1563-1578. [PMID: 36690886 DOI: 10.1007/s00394-023-03085-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 01/03/2023] [Indexed: 01/25/2023]
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition. Low-grade chronic inflammation contributes to disease progression. Diet has protective effects on hepatic health and inflammatory pathways. The purpose of this review is to systematically review and describe the effects of anti-inflammatory dietary patterns on NAFLD. METHODS The Cochrane CENTRAL Library, Cumulative Index of Nursing and Allied Health Literature, Embase, MEDLINE and Web of Science databases were searched. A total of 252 records were identified, 7 of which were included in this review. The revised Cochrane risk-of-bias tool was used to conduct a quality assessment for randomised trials. Certainty of evidence was assessed using the grading of recommendations, assessment, development, and evaluation tool. RESULTS Of the 7 included studies, 6 were classified as low risk of bias and studies ranged from high to very low certainty of evidence. In the randomised-controlled studies systematically reviewed, either adherence to the Mediterranean, DASH, or FLiO diet was studied, against usual care or energy matched controls, with a total of 255 participants. Anti-inflammatory dietary pattern adherence significantly reduced the severity of most hepatic and inflammatory markers, and secondary outcomes. A minority of outcomes were improved significantly more than controls. CONCLUSION Anti-inflammatory dietary patterns showed benefits to NAFLD risk factors, severity markers and inflammatory markers compared to the control diet. It is unclear whether reductions in the evaluated parameters are related solely to the anti-inflammatory diet or weight loss resulting from caloric restriction, as improvements in control groups were also evidenced. Current limited body of evidence indicates need for further research including isocaloric dietary patterns, longer interventions, measures of inflammatory markers, and studies including normal-weight subjects to confirm findings at higher certainty. PROSPERO REGISTRATION CRD42021269382.
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Kim MJ, Kim MS, Lee HB, Roh JH, Jeon JH. Relationship between the High Fatty Liver Index and Risk of Fracture. Gut Liver 2023; 17:119-129. [PMID: 35892266 PMCID: PMC9840917 DOI: 10.5009/gnl210571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 04/15/2022] [Accepted: 05/03/2022] [Indexed: 02/01/2023] Open
Abstract
Background/Aims The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased rapidly as a consequence of more sedentary lifestyles and a Westernized diet. Fracture is a major clinical problem in older people, but few large-scale cohort studies have evaluated the relationship between NAFLD and fracture. Therefore, we aimed to determine whether the fatty liver index (FLI), which represents the severity of NAFLD, can predict fracture risk. Methods We analyzed the relationship between the FLI and incident fracture using multivariate Cox proportional hazards models and data for 180,519 individuals who underwent National Health check-ups in the Republic of Korea between 2009 and 2014. Results A total of 2,720 participants (1.5%) were newly diagnosed with fracture during the study period (median 4.6 years). The participants were grouped according to FLI quartiles (Q1, 0 to <5.653; Q2, 5.653 to <15.245; Q3, 15.245 to <37.199; and Q4 ≥37.199). The cumulative fracture incidence was significantly higher in the highest FLI group than in the lowest FLI group (Q4, 986 [2.2%] and Q1, 323 [0.7%]; p<0.001). The adjusted hazard ratio indicated that the highest FLI group was independently associated with a higher incidence of fracture (hazard ratio for Q4 vs Q1, 2.956; 95% confidence interval, 2.606 to 3.351; p<0.001). FLI was significantly associated with a higher incidence of fracture, independent of the baseline characteristics of the participants. Conclusions Our data imply that the higher the FLI of a Korean patient is, the higher their risk of osteoporotic fracture, independent of key confounding factors. (Gut Liver, Published online July 27, 2022).
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Affiliation(s)
- Min-Ji Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Min-Su Kim
- Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Korea
| | - Han-Byul Lee
- Department of Statistics, Kyungpook National University, Daegu, Korea
| | - Jae-Hyung Roh
- Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Korea
| | - Jae-Han Jeon
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
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Choi SW, Oh H, Park SY, Cho W, El-Aty AA, Baygutalp NK, Jeong JH, Jung TW. Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress. Life Sci 2022; 311:121149. [DOI: 10.1016/j.lfs.2022.121149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/29/2022] [Accepted: 10/31/2022] [Indexed: 11/17/2022]
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Chaplin A, Rodriguez RM, Segura-Sampedro JJ, Ochogavía-Seguí A, Romaguera D, Barceló-Coblijn G. Insights behind the Relationship between Colorectal Cancer and Obesity: Is Visceral Adipose Tissue the Missing Link? Int J Mol Sci 2022; 23:13128. [PMID: 36361914 PMCID: PMC9655590 DOI: 10.3390/ijms232113128] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 10/21/2022] [Accepted: 10/25/2022] [Indexed: 09/05/2023] Open
Abstract
Colorectal cancer (CRC) is a major health problem worldwide, with an estimated 1.9 million new cases and 915,880 deaths in 2020 alone. The etiology of CRC is complex and involves both genetic and lifestyle factors. Obesity is a major risk factor for CRC, and the mechanisms underlying this link are still unclear. However, the generalized inflammatory state of adipose tissue in obesity is thought to play a role in the association between CRC risk and development. Visceral adipose tissue (VAT) is a major source of proinflammatory cytokines and other factors that contribute to the characteristic systemic low-grade inflammation associated with obesity. VAT is also closely associated with the tumor microenvironment (TME), and recent evidence suggests that adipocytes within the TME undergo phenotypic changes that contribute to tumor progression. In this review, we aim to summarize the current evidence linking obesity and CRC, with a focus on the role of VAT in tumor etiology and progression.
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Affiliation(s)
- Alice Chaplin
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Ramon Maria Rodriguez
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
| | - Juan José Segura-Sampedro
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
- General & Digestive Surgery Department, University Hospital Son Espases, 07120 Palma, Spain
- School of Medicine, University of the Balearic Islands, 07120 Palma, Spain
| | - Aina Ochogavía-Seguí
- General & Digestive Surgery Department, University Hospital Son Espases, 07120 Palma, Spain
| | - Dora Romaguera
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Gwendolyn Barceló-Coblijn
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
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Huang H, Guo Y, Liu Z, Zeng Y, Chen Y, Xu C. Remnant Cholesterol Predicts Long-term Mortality of Patients With Metabolic Dysfunction-associated Fatty Liver Disease. J Clin Endocrinol Metab 2022; 107:e3295-e3303. [PMID: 35521833 DOI: 10.1210/clinem/dgac283] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Indexed: 01/04/2023]
Abstract
CONTEXT Elevated serum remnant cholesterol independently predicts risks of cardiovascular diseases. However, the association between remnant cholesterol and metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. OBJECTIVE This study aimed to explore the association of remnant cholesterol with MAFLD and its long-term mortality. METHODS We extracted data from the NHANES III, 1988 to1994 and the linked mortality data until December 31, 2015. The association between remnant cholesterol and MAFLD was analyzed by multivariable logistic regression. Cox proportional hazards regression was performed to assess whether elevated remnant cholesterol increased all-cause and cause-specific mortalities in MAFLD patients. RESULTS At baseline, 28.6% (1474/5156) of participants had MAFLD. In multivariable logistic regression, the fourth quartile of remnant cholesterol was associated with an increased risk of MAFLD compared with the first quartile (odds ratio [OR]: 1.714; 95% CI, 1.586-1.971; P < .001). In participants with normal levels of triglycerides, low-density lipoprotein and high-density lipoprotein cholesterol, the relationship between remnant cholesterol and MAFLD risk remained significant (OR: 1.346; 95% CI, 1.248-1.761; P < .001). During a median follow-up of 307 months, MAFLD patients with serum remnant cholesterol in the fourth quartile were associated with a higher risk of all-cause mortality (hazard ratio [HR]: 2.183; 95% CI, 1.825-2.407; P < .001), as well as a higher risk of cardiovascular mortality (HR: 2.346; 95% CI, 2.046-2.885; P < .001) and cancer-related mortality (HR: 2.366; 95% CI, 1.864-2.932; P < .001) compared with MAFLD patients in the first quartile. CONCLUSION Remnant cholesterol was independently associated with the risk of MAFLD and predicted all-cause, cardiovascular, and cancer-related mortalities in MAFLD patients.
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Affiliation(s)
- Hangkai Huang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yanjun Guo
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Zhening Liu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yan Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yishu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Chengfu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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Kociszewska D, Vlajkovic S. Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis. Int J Mol Sci 2022; 23:7348. [PMID: 35806352 PMCID: PMC9266910 DOI: 10.3390/ijms23137348] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/30/2022] [Accepted: 06/30/2022] [Indexed: 12/12/2022] Open
Abstract
This article provides a theoretical overview of the association between age-related hearing loss (ARHL), immune system ageing (immunosenescence), and chronic inflammation. ARHL, or presbyacusis, is the most common sensory disability that significantly reduces the quality of life and has a high economic impact. This disorder is linked to genetic risk factors but is also influenced by a lifelong cumulative effect of environmental stressors, such as noise, otological diseases, or ototoxic drugs. Age-related hearing loss and other age-related disorders share common mechanisms which often converge on low-grade chronic inflammation known as "inflammaging". Various stimuli can sustain inflammaging, including pathogens, cell debris, nutrients, and gut microbiota. As a result of ageing, the immune system can become defective, leading to the accumulation of unresolved inflammatory processes in the body. Gut microbiota plays a central role in inflammaging because it can release inflammatory mediators and crosstalk with other organ systems. A proinflammatory gut environment associated with ageing could result in a leaky gut and the translocation of bacterial metabolites and inflammatory mediators to distant organs via the systemic circulation. Here, we postulate that inflammaging, as a result of immunosenescence and gut dysbiosis, accelerates age-related cochlear degeneration, contributing to the development of ARHL. Age-dependent gut dysbiosis was included as a hypothetical link that should receive more attention in future studies.
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Affiliation(s)
| | - Srdjan Vlajkovic
- Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, Auckland 1142, New Zealand;
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Shojaei‐Zarghani S, Safarpour AR, Fattahi MR, Keshtkar A. Sodium in relation with nonalcoholic fatty liver disease: A systematic review and meta-analysis of observational studies. Food Sci Nutr 2022; 10:1579-1591. [PMID: 35592291 PMCID: PMC9094449 DOI: 10.1002/fsn3.2781] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 01/06/2022] [Accepted: 01/25/2022] [Indexed: 12/11/2022] Open
Abstract
Findings on the association of sodium with nonalcoholic fatty liver disease (NAFLD) are conflicting. The present systematic review and meta‐analysis study aimed to assess the association between salt or sodium intake or serum sodium levels and NAFLD risk. Relevant articles were identified by searching PubMed, Web of Knowledge, Scopus, Proquest, and Embase databases through May 1, 2021, without language restriction. The pooled odds ratio (OR) and 95% confidence interval (CI) were estimated using Der‐Simonian and Laird method and random‐effects meta‐analysis. The certainty of the evidence was rated using the GRADE method. Out of 6470 documents, 7 epidemiological/observational (1 cohort, 1 case–control, and 5 cross‐sectional) studies on the relationship between dietary salt/sodium intakes and NAFLD risk met our inclusion criteria. The meta‐analysis of all studies showed a significant positive association between the highest salt/sodium intake and NALFD risk (OR = 1.60, 95% CI: 1.19–2.15) with a meaningful heterogeneity among studies (I2 = 96.70%, p‐value <.001). The NAFLD risk was greater in the studies with higher quality (OR = 1.81, 95% CI: 1.24–2.65) or using the equation‐based methods for NAFLD ascertainment (OR = 2.02, 95% CI: 1.29–3.17) or urinary sodium collection as a sodium intake assessment (OR = 2.48, 95% CI: 1.52–4.06). The overall certainty of the evidence was very low. In conclusion, high sodium intake seems to be related to increased NAFLD risk. Further well‐designed studies are needed to clarify this association and shed light on the underlying mechanisms.
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Affiliation(s)
- Sara Shojaei‐Zarghani
- Gastroenterohepatology Research CenterShiraz University of Medical SciencesShirazIran
| | - Ali Reza Safarpour
- Gastroenterohepatology Research CenterShiraz University of Medical SciencesShirazIran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research CenterShiraz University of Medical SciencesShirazIran
| | - Abbasali Keshtkar
- Department of Health Sciences Education DevelopmentSchool of Public HealthTehran University of Medical SciencesTehranIran
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Akter S. Non-alcoholic Fatty Liver Disease and Steatohepatitis: Risk Factors and Pathophysiology. Middle East J Dig Dis 2022; 14:167-181. [PMID: 36619154 PMCID: PMC9489315 DOI: 10.34172/mejdd.2022.270] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 01/20/2022] [Indexed: 01/11/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its progressive subtype non-alcoholic steatohepatitis (NASH) are the most prevalent liver diseases, often leading to hepatocellular carcinoma (HCC). This review aims to describe the present knowledge of the risk factors responsible for the development of NAFLD and NASH. I performed a literature review identifying studies focusing on the complex pathogenic pathway and risk factors of NAFLD and steatohepatitis. The relationship between NAFLD and metabolic syndrome is well established and widely recognized. Obesity, dyslipidemia, type 2 diabetes, hypertension, and insulin resistance are the most common risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly suggests obesity and type 2 diabetes as risk factors of NASH and HCC. However, other elements, namely gender divergences, ethnicity, genetic factors, participation of innate immune system, oxidative stress, apoptotic pathways, and adipocytokines, take a leading role in the onset and promotion of NAFLD. Pathophysiological mechanisms that are responsible for NAFLD development and subsequent progression to NASH are insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell (HSC) activation, cytokine/adipokine signaling pathways, and genetic and environmental factors. Major pathophysiological findings of NAFLD are dysfunction of adipose tissue through the enhanced flow of free fatty acids (FFAs) and release of adipokines, and altered gut microbiome that generate proinflammatory signals and cause NASH progression. Understanding the pathophysiology and risk factors of NAFLD and NASH; this review could provide insight into the development of therapeutic strategies and useful diagnostic tools.
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Affiliation(s)
- Sharmin Akter
- Department of Physiology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh,Corresponding Author: Sharmin Akter, PhD Department of Physiology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh Tel: +0088-091-67401-6 (ext. 6320) Fax: + 880 91 61510
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Ghezelbash B, Shahrokhi N, Khaksari M, Asadikaram G, Shahrokhi M, Shirazpour S. Protective Roles of Shilajit in Modulating Resistin, Adiponectin, and Cytokines in Rats with Non-alcoholic Fatty Liver Disease. Chin J Integr Med 2022; 28:531-537. [PMID: 35258780 DOI: 10.1007/s11655-022-3307-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD). METHODS After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated. RESULTS After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05). CONCLUSION The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.
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Affiliation(s)
- Baran Ghezelbash
- Physiology Research Center, Kerman University of Medical Sciences, Kerman, 7616914115, Iran
| | - Nader Shahrokhi
- Physiology Research Center, Kerman University of Medical Sciences, Kerman, 7616914115, Iran.
| | - Mohammad Khaksari
- Endocrinology, and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, 7616914115, Iran
| | - Gholamreza Asadikaram
- Department of Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, 7616914115, Iran
| | - Maryam Shahrokhi
- Department of Medical Science, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, 713414336, Iran
| | - Sara Shirazpour
- Department of Physiology and Pharmacology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, 7616914115, Iran
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Hegazy W, Abdel-Moneim A, Abdel-Rehiem ES, Salah M, Abdul-Hamid M. The protective effect of hesperidin on the liver of hypothyroid rats mediated by nuclear factor erythroid 2-related factor 2-dependent activation of heme oxygenase 1. J Mol Histol 2022; 53:543-560. [DOI: 10.1007/s10735-022-10066-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 02/08/2022] [Indexed: 10/19/2022]
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Chen XY, Wang C, Huang YZ, Zhang LL. Nonalcoholic fatty liver disease shows significant sex dimorphism. World J Clin Cases 2022; 10:1457-1472. [PMID: 35211584 PMCID: PMC8855265 DOI: 10.12998/wjcc.v10.i5.1457] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 12/02/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.
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Affiliation(s)
- Xing-Yu Chen
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Cong Wang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Yi-Zhou Huang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Li-Li Zhang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
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Lee DH, Lee IH, Hong JT. Fermented field water-dropwort (Oenanthe javanica) alleviates diet-induced non-alcoholic steatohepatitis. FOOD AGR IMMUNOL 2022. [DOI: 10.1080/09540105.2021.2022603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Dong Hun Lee
- Department of Biological Sciences, Chonnam National University, Gwangju, Republic of Korea
| | - Il Ho Lee
- OSBio, Co. Ltd., Cheongju, Republic of Korea
| | - Jin Tae Hong
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea
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Liu X, Sun R, Li Z, Xiao R, Lv P, Sun X, Olson MA, Gong Y. Luteolin alleviates non-alcoholic fatty liver disease in rats via restoration of intestinal mucosal barrier damage and microbiota imbalance involving in gut-liver axis. Arch Biochem Biophys 2021; 711:109019. [PMID: 34478730 DOI: 10.1016/j.abb.2021.109019] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/19/2021] [Accepted: 08/19/2021] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is demonstrated to be closely related to the disorder of gut microbiota and the intestinal mucosal barrier. Luteolin is a natural flavonoid with various activities. We aimed to investigate whether Luteolin can alleviate NAFLD and its possible mechanism involving the gut-liver axis. A rat NAFLD model was established by feeding a high-fat diet (HFD), and Luteolin was administered intragastrically. The effects of Luteolin on liver biochemical parameters, intestinal histopathology and integrity, gut microbiota, lipopolysaccharides (LPS), inflammatory cytokines, and the Toll-like receptor 4 (TLR4) signaling pathway were evaluated. We found that Luteolin restored the expression of the tight junction proteins in the intestine and ameliorated the increase permeability of the intestinal mucosa to Fluorescein isothiocyanate-dextran (FD4) caused by a high-fat diet, thus enhancing the function of the intestinal barrier. In addition, Luteolin inhibited the TLR4 signaling pathway in the liver, thereby reducing the secretion of pro-inflammatory factors and alleviating NAFLD. 16S rRNA gene sequencing revealed that Luteolin intervention significantly altered the composition of the gut microbiota in NAFLD rats and increased the richness of gut microbiota. Luteolin alleviates NAFLD in rats via restoration and repair of the damaged intestinal mucosal barrier and microbiota imbalance.
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Affiliation(s)
- Xia Liu
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China
| | - Runzhou Sun
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China
| | - Zhaozhen Li
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China
| | - Ruixin Xiao
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China
| | - Pengfei Lv
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China
| | - Xiangrong Sun
- Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Mark A Olson
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China; Department of Chemistry, Northwestern University, Evanston, IL, USA
| | - Yanling Gong
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
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Bazard P, Pineros J, Frisina RD, Bauer MA, Acosta AA, Paganella LR, Borakiewicz D, Thivierge M, Mannering FL, Zhu X, Ding B. Cochlear Inflammaging in Relation to Ion Channels and Mitochondrial Functions. Cells 2021; 10:2761. [PMID: 34685743 PMCID: PMC8534887 DOI: 10.3390/cells10102761] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/06/2021] [Accepted: 10/12/2021] [Indexed: 12/20/2022] Open
Abstract
The slow accumulation of inflammatory biomarker levels in the body-also known as inflammaging-has been linked to a myriad of age-related diseases. Some of these include neurodegenerative conditions such as Parkinson's disease, obesity, type II diabetes, cardiovascular disease, and many others. Though a direct correlation has not been established, research connecting age-related hearing loss (ARHL)-the number one communication disorder and one of the most prevalent neurodegenerative diseases of our aged population-and inflammaging has gained interest. Research, thus far, has found that inflammatory markers, such as IL-6 and white blood cells, are associated with ARHL in humans and animals. Moreover, studies investigating ion channels and mitochondrial involvement have shown promising relationships between their functions and inflammaging in the cochlea. In this review, we summarize key findings in inflammaging within the auditory system, the involvement of ion channels and mitochondrial functions, and lastly discuss potential treatment options focusing on controlling inflammation as we age.
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Affiliation(s)
- Parveen Bazard
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Jennifer Pineros
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Robert D. Frisina
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
- Department Communication Sciences and Disorders, College of Behavioral & Communication Sciences, Tampa, FL 33620, USA
- Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Mark A. Bauer
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Alejandro A. Acosta
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Lauren R. Paganella
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Dominika Borakiewicz
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Mark Thivierge
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Freyda L. Mannering
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
- Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Xiaoxia Zhu
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
| | - Bo Ding
- Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; (P.B.); (J.P.); (M.A.B.); (A.A.A.); (L.R.P.); (D.B.); (M.T.); (X.Z.); (B.D.)
- Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA;
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Cerebrovascular alterations in NAFLD: Is it increasing our risk of Alzheimer's disease? Anal Biochem 2021; 636:114387. [PMID: 34537182 DOI: 10.1016/j.ab.2021.114387] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/27/2021] [Accepted: 09/15/2021] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, which has been classified as an emerging epidemic not only confined to liver-related morbidity and mortality. It is also becoming apparent that NAFLD is associated with moderate cerebral dysfunction and cognitive decline. A possible link between NAFLD and Alzheimer's disease (AD) has only recently been proposed due to the multiple shared genes and pathological mechanisms contributing to the development of these conditions. Although AD is a progressive neurodegenerative disease, the exact pathophysiological mechanism remains ambiguous and similarly to NAFLD, currently available pharmacological therapies have mostly failed in clinical trials. In addition to the usual suspects (inflammation, oxidative stress, blood-brain barrier alterations and ageing) that could contribute to the NAFLD-induced development and progression of AD, changes in the vasculature, cerebral perfusion and waste clearance could be the missing link between these two diseases. Here, we review the most recent literature linking NAFLD and AD, focusing on cerebrovascular alterations and the brain's clearance system as risk factors involved in the development and progression of AD, with the aim of promoting further research using neuroimaging techniques and new mechanism-based therapeutic interventions.
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Tarantino G, Citro V, Cataldi M. Findings from Studies Are Congruent with Obesity Having a Viral Origin, but What about Obesity-Related NAFLD? Viruses 2021; 13:1285. [PMID: 34372491 PMCID: PMC8310150 DOI: 10.3390/v13071285] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/26/2021] [Accepted: 06/26/2021] [Indexed: 02/06/2023] Open
Abstract
Infection has recently started receiving greater attention as an unusual causative/inducing factor of obesity. Indeed, the biological plausibility of infectobesity includes direct roles of some viruses to reprogram host metabolism toward a more lipogenic and adipogenic status. Furthermore, the probability that humans may exchange microbiota components (virome/virobiota) points out that the altered response of IFN and other cytokines, which surfaces as a central mechanism for adipogenesis and obesity-associated immune suppression, is due to the fact that gut microbiota uphold intrinsic IFN signaling. Last but not least, the adaptation of both host immune and metabolic system under persistent viral infections play a central role in these phenomena. We hereby discuss the possible link between adenovirus and obesity-related nonalcoholic fatty liver disease (NAFLD). The mechanisms of adenovirus-36 (Ad-36) involvement in hepatic steatosis/NAFLD consist in reducing leptin gene expression and insulin sensitivity, augmenting glucose uptake, activating the lipogenic and pro-inflammatory pathways in adipose tissue, and increasing the level of macrophage chemoattractant protein-1, all of these ultimately leading to chronic inflammation and altered lipid metabolism. Moreover, by reducing leptin expression and secretion Ad-36 may have in turn an obesogenic effect through increased food intake or decreased energy expenditure via altered fat metabolism. Finally, Ad-36 is involved in upregulation of cAMP, phosphatidylinositol 3-kinase, and p38 signaling pathways, downregulation of Wnt10b expression, increased expression of CCAAT/enhancer binding protein-beta, and peroxisome proliferator-activated receptor gamma 2 with consequential lipid accumulation.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, “Federico II” University Medical School of Naples, 80131 Napoli, Italy
| | - Vincenzo Citro
- Department of General Medicine, “Umberto I” Hospital, Nocera Inferiore (Sa), 84014 Nocera Inferiore, Italy;
| | - Mauro Cataldi
- Section of Pharmacology, Department of Neuroscience, Reproductive Sciences and Dentistry, “Federico II” University of Naples, 80131 Napoli, Italy;
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Tarantino G, Citro V, Balsano C. Liver-spleen axis in nonalcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2021; 15:759-769. [PMID: 33878988 DOI: 10.1080/17474124.2021.1914587] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 04/06/2021] [Indexed: 01/06/2023]
Abstract
Introduction: NAFLD is often under-diagnosed, even though rates of its co-morbidities such as obesity and type2 diabetes mellitus, prominent statuses of inflammation, are significantly high. The spleen-liver axis is gaining much credit in the last years like other well-known organ axes.Areas covered: PubMed/MEDLINE was searched for relevant articles related to concomitant occurrence of NAFLD and spleen. Areas covered in this review include: (1) updated findings of spleen dimensions at ultrasonography, (2) discussion of current data on pathophysiological connections between obesity-related NAFLD and increased volume of the spleen, and (3) analysis of current immune-mediated mechanisms characterizing the so.called chronic low-grade inflammation leading to insulin resistance.Expert opinion: The advances in explaining mechanisms underlying the spleen involvement in immune regulation, coupled with research about the role of spleen in NAFLD, could impact real world outcomes through establishing better tools for a precocious diagnosis. Using both liver and spleen ultrasonography, technique largely dealt with in this review, could expand the possibility to cover an adequate diagnostic path toward NAFLD, reaching a good sensibility and specificity.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, Naples, Italy
| | - Vincenzo Citro
- Department of General Medicine, "Umberto I" Hospital, Nocera Inferiore (SA), Nocera Inferiore, Italy
| | - Clara Balsano
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, L'Aquila, Italy
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Wu AJ, Rifas-Shiman SL, Taveras EM, Oken E, Hivert MF. Associations of DXA-measured abdominal adiposity with cardio-metabolic risk and related markers in early adolescence in Project Viva. Pediatr Obes 2021; 16:e12704. [PMID: 32761791 PMCID: PMC7790849 DOI: 10.1111/ijpo.12704] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 06/29/2020] [Accepted: 07/02/2020] [Indexed: 01/23/2023]
Abstract
BACKGROUND Increased visceral adipose tissue (VAT) precedes development of insulin resistance and dyslipidemia in adults. The associations of abdominal adiposity derived from dual-energy X-ray absorptiometry (DXA), including VAT, subcutaneous abdominal adipose tissue (SAAT) and total abdominal adipose tissue (TAAT) with cardio-metabolic risk in adolescents are understudied. OBJECTIVES We examined the cross-sectional associations of DXA-measured abdominal adiposity with cardio-metabolic risk and related markers in early adolescence (mean [SD] age 13.0 [0.7] years). METHODS We collected data from 740 adolescents (374 girls and 366 boys) in Project Viva, a U.S. pre-birth cohort. We used DXA estimates of VAT, SAAT and TAAT area. We conducted overall and sex-stratified linear regression models, adjusting for age, sex (in overall models), race/ethnicity, puberty score and body mass index (BMI) z-score. RESULTS Mean BMI z-score was 0.59 (1.28). After adjustment, greater VAT (per 1 SD score) was associated with higher metabolic risk z-score (β 0.14 units; 95% CI 0.08, 0.20), higher log high-sensitivity C-reactive protein (β 0.51 mg/L; 0.36, 0.66) and log leptin (β 0.36 ng/mL; 0.27, 0.44), and lower log adiponectin (β -0.08 ug/mL; -0.13, -0.02). SAAT and TAAT showed similar associations as VAT with comparable or greater effect sizes. CONCLUSION In early adolescence, DXA-measured VAT, SAAT and TAAT are associated with cardio-metabolic risk and related markers, independent of current BMI. Among two adolescents with the same BMI, there is an associated higher cardio-metabolic risk in the adolescent with greater DXA-measured abdominal adiposity.
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Affiliation(s)
- Allison J. Wu
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.,Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, MA, USA
| | - Sheryl L. Rifas-Shiman
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Elsie M. Taveras
- Division of General Academic Pediatrics, Massachusetts General Hospital for Children, Boston, Massachusetts, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Emily Oken
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Marie-France Hivert
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
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48
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Foisy Sauvé M, Spahis S, Delvin E, Levy E. Glycomacropeptide: A Bioactive Milk Derivative to Alleviate Metabolic Syndrome Outcomes. Antioxid Redox Signal 2021; 34:201-222. [PMID: 32338040 DOI: 10.1089/ars.2019.7994] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Significance: Metabolic syndrome (MetS) represents a cluster of cardiometabolic disorders, which accelerate the risk of developing diabetes, nonalcoholic fatty liver disease, and cardiovascular disorders such as atherosclerosis. Oxidative stress (OxS) and inflammation contribute to insulin resistance (IR) that greatly promotes the clinical manifestations of MetS components. Given the growing prevalence of this multifactorial condition, its alerting comorbidities, and the absence of specific drugs for treatment, there is an urgent need of prospecting for alternative nutraceutics as effective therapeutic agents for MetS. Recent Advances: There is a renewed interest in bioactive peptides derived from human and bovine milk proteins given their high potential in magnifying health benefits. Special attention has been paid to glycomacropeptide (GMP), a bioactive and soluble derivative from casein and milk whey, because of the wide range of its health-promoting functions perceived in the MetS and related complications. Critical Issues: In the present review, the challenging issue relative to clinical utility of GMP in improving MetS outcomes will be critically reported. Its importance in alleviating obesity, OxS, inflammation, IR, dyslipidemia, and hypertension will be underlined. The mechanisms of action will be analyzed, and the various gaps of knowledge in this area will be specified. Future Directions: Valuable data from cellular, preclinical, and clinical investigations have emphasized the preventive and therapeutic actions of GMP toward the MetS. However, additional efforts are needed to support its proofs of principle and causative relationship to translate its concept into the clinic. Antioxid. Redox Signal. 34, 201-222.
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Affiliation(s)
- Mathilde Foisy Sauvé
- Research Centre, CHU Sainte-Justine, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada
| | - Schohraya Spahis
- Research Centre, CHU Sainte-Justine, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada
| | - Edgard Delvin
- Research Centre, CHU Sainte-Justine, Montreal, Canada
| | - Emile Levy
- Research Centre, CHU Sainte-Justine, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada
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Čolak E, Pap D. The role of oxidative stress in the development of obesity and obesity-related metabolic disorders. J Med Biochem 2021; 40:1-9. [PMID: 33584134 PMCID: PMC7857849 DOI: 10.5937/jomb0-24652] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 01/30/2020] [Indexed: 12/21/2022] Open
Abstract
Obesity is a serious medical condition, defined as excessive accumulation of fat. Abdominal fat is recognized as the major risk for obesity related diseases such as: hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, stroke, non-alcoholic fatty liver disease etc. Fat accumulation is also related to pro-oxidant and pro-inflammatory states. Recently published articles suggest that oxidative stress may be a link between obesity and related complications. Adiposity leads to increased oxidative stress via several multiple biochemical processes such as superoxide generation through the action of NADPH oxidase, glyceraldehyde auto-oxidation, oxidative phosphorylation, protein kinase C (PKC) activation, and polyol and hexosamine pathways. On the other hand, oxidative stress plays a causative role in the development of obesity, by stimulating the deposition of adipose tissue, including preadipocyte proliferation, adipocyte differentiation and growth. Exercise-induced weight loss can improve the redox state by modulating both oxidative stress and antioxidant promoters, which reduce endothelial dysfunction and inflammation.
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Affiliation(s)
- Emina Čolak
- Clinical Center of Serbia, Institute of Medical Biochemistry, Department for Scientific Research and Education, Belgrade
| | - Dragana Pap
- Students Health Protection Institute, Department of Laboratory Diagnostics, Novi Sad
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50
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Increased risk of acute liver failure by pain killer drugs in NAFLD: Focus on nuclear receptors and their coactivators. Dig Liver Dis 2021; 53:26-34. [PMID: 32546444 DOI: 10.1016/j.dld.2020.05.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 05/05/2020] [Accepted: 05/18/2020] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a global condition characterized by an accumulation of lipids in the hepatocytes. NAFLD ranges from simple steatosis, a reversible and relatively benign condition, to fibrosis with non-alcoholic steatohepatitis (NASH), potentially leading to cirrhosis and hepatocarcinoma. NAFLD can increase the susceptibility to severe liver injury with eventual acute liver failure induced by specific hepatotoxic drugs, including acetaminophen (APAP), which is commonly used as analgesic and antipyretic. Although several animal models have been used to clarify the predisposing role of hepatic steatosis to APAP intoxication, the exact mechanism is still not clear. Here, we shed a light into the association between NAFLD and APAP toxicity by examining the peculiar role of nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and coactivator peroxisome proliferator-activated receptor gamma coactivator 1-β (PGC-1β) in driving fatty acid metabolism, inflammation and mitochondria redox balance. The knowledge of the mechanism that exposes patients with NAFLD to higher risk of acute liver failure by pain killer drug is the first step to eventually claim for a reduction of the maximal diurnal dose of APAP for subjects with liver steatosis.
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