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Xiang Q, Wen J, Zhou Z, Dai Q, Huang Y, Yang N, Guo J, Zhang J, Ren F, Zhou X, Rao C, Chen Y. Effect of hydroxy-α-sanshool on lipid metabolism in liver and hepatocytes based on AMPK signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155849. [PMID: 38964152 DOI: 10.1016/j.phymed.2024.155849] [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: 03/24/2024] [Revised: 05/30/2024] [Accepted: 06/26/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND With the increasing awareness of the safety of traditional Chinese medicine and food, as well as in-depth studies on the pharmacological activity and toxicity of Zanthoxylum armatum DC. (ZADC), it has been found that ZADC is hepatotoxic. However, the toxic substance basis and mechanism of action have not been fully elucidated. Hydroxy-α-sanshool (HAS) belongs to an amide compound in the fruits of ZADC, which may be hepatotoxic. However, the specific effects of HAS, including liver toxicity, are unclear. PURPOSE The objectives of this research was to determine how HAS affects hepatic lipid metabolism, identify the mechanism underlying the accumulation of liver lipids by HAS, and offer assurances on the safe administration of HAS. METHODS An in vivo experiment was performed by gavaging C57 BL/6 J mice with various dosages of HAS (5, 10, and 20 mg/kg). Biochemical indexes were measured, and histological analysis was performed to evaluate HAS hepatotoxicity. Hepatic lipid levels were determined using lipid indices and oil red O (ORO) staining. Intracellular lipid content were determined by biochemical analyses and ORO staining after treating HepG2 cells with different concentrations of HAS in vitro. Mitochondrial membrane potential, respiratory chain complex enzymes, and ATP levels were assessed by fluorescence labeling of mitochondria. The levels of proteins involved in lipogenesis and catabolism were determined using Western blotting. RESULTS Mice in the HAS group had elevated alanine and aspartate aminotransferase blood levels as well as increased liver index compared with the controls. The pathological findings showed hepatocellular necrosis. Serum and liver levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were increased, whereas high-density lipoprotein cholesterol levels decreased. The ORO staining findings demonstrated elevated liver lipid levels. In vitro experiments demonstrated a notable elevation in triglyceride and total cholesterol levels in the HAS group. ATP, respiratory chain complex enzyme gene expression, mitochondrial membrane potential, and mitochondrial number were reduced in the HAS group. The levels of lipid synthesis-associated proteins (ACC, FASN, and SREBP-1c) were increased, and lipid catabolism-associated protein levels (PPARα and CPT1) and the p-AMPK/AMPK ratio were decreased in vivo and in vitro. CONCLUSION HAS has hepatotoxic effects, which can induce fatty acid synthesis and mitochondrial function damage by inhibiting the AMPK signaling pathway, resulting in aberrant lipid increases.
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Affiliation(s)
- Qiwen Xiang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jiayu Wen
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Zhihui Zhou
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qiuju Dai
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yan Huang
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu 611137, China
| | - Nannan Yang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jiafu Guo
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jian Zhang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Fajian Ren
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xinyi Zhou
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Chaolong Rao
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu 611137, China; R&D Center for Efficiency, Safety and Application in Chinese Materia Medica with Medical and Edible Values, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
| | - Yan Chen
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu 611137, China; R&D Center for Efficiency, Safety and Application in Chinese Materia Medica with Medical and Edible Values, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
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Fu DF, Chen B. The relationship between the systemic immune inflammation index and the nonalcoholic fatty liver disease in American adolescents. BMC Gastroenterol 2024; 24:233. [PMID: 39044158 PMCID: PMC11267776 DOI: 10.1186/s12876-024-03324-6] [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: 02/23/2024] [Accepted: 07/15/2024] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. METHODS We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. RESULTS A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases. CONCLUSION There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.
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Affiliation(s)
- Dong-Fang Fu
- Department of Ultrasound, Hangzhou Xiaoshan First People's Hospital, No.199, Shixin South Road, Xiaoshan District, Hangzhou, Zhejiang, 311201, China
| | - Bin Chen
- Department of Ultrasound, Hangzhou Xiaoshan First People's Hospital, No.199, Shixin South Road, Xiaoshan District, Hangzhou, Zhejiang, 311201, China.
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Maleki Sedgi F, Mohammad Hosseiniazar M, Alizadeh M. The effects of replacing ghee with rapeseed oil on liver steatosis and enzymes, lipid profile, insulin resistance and anthropometric measurements in patients with non-alcoholic fatty liver disease: a randomised controlled clinical trial. Br J Nutr 2024; 131:1985-1996. [PMID: 38501177 DOI: 10.1017/s0007114524000564] [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] [Indexed: 03/20/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD), which is a prevalent hepatic condition worldwide, is expected to develop into the leading reason for end-stage fatty liver in the forthcoming decades. Incorporating rapeseed oil into a balanced diet may be beneficial in improving NAFLD. The goal of this trial was to evaluate the impact of substituting ghee with rapeseed oil on primary outcomes such as fatty liver and liver enzymes, as well as on secondary outcomes including glycaemic variables, lipid profile and anthropometric measurements in individuals with NAFLD. Over 12 weeks, 110 patients (seventy men and forty women; BMI (mean) 28·2 (sd 1·6 kg/m2); mean age 42 (sd 9·6) years), who daily consumed ghee, were assigned to the intervention or control group through random allocation. The intervention group was advised to substitute ghee with rapeseed oil in the same amount. The control group continued the consumption of ghee and was instructed to adhere to a healthy diet. Results showed a significant reduction in the steatosis in the intervention group in comparison with the control group (P < 0·001). However, a significant change in the levels of alanine aminotransferase (–14·4 μg/l), γ-glutamyl transferase (–1·8 μg/l), TAG (–39·7 mg/dl), total cholesterol (–17·2 mg/dl), LDL (–7·5 mg/dl), fasting blood glucose (–7·5 mg/dl), insulin (–3·05 mU/l), Homeostatic Model Assessment for Insulin Resistance (–0·9), Quantitative Insulin-Sensitivity Check Index (+0·01), weight (–4·3 kg), BMI (–0·04 kg/m2), waist (–5·6 cm) and waist:height ratio (–0·04) was seen in the intervention group. The consumption of rapeseed oil instead of ghee caused improvements in liver steatosis and enzymes, glycaemic variables and anthropometric measurements among individuals with NAFLD.
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Affiliation(s)
- Fatemeh Maleki Sedgi
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | | | - Mohammad Alizadeh
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran
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Rimoldi S, Di Rosa AR, Oteri M, Chiofalo B, Hasan I, Saroglia M, Terova G. The impact of diets containing Hermetia illucens meal on the growth, intestinal health, and microbiota of gilthead seabream (Sparus aurata). FISH PHYSIOLOGY AND BIOCHEMISTRY 2024; 50:1003-1024. [PMID: 38386264 PMCID: PMC11213805 DOI: 10.1007/s10695-024-01314-9] [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: 09/17/2023] [Accepted: 01/29/2024] [Indexed: 02/23/2024]
Abstract
The present study investigated the effect of replacing fishmeal (FM) with insect meal of Hermetia illucens (HI) in the diet of Sparus aurata farmed inshore on growth, gut health, and microbiota composition. Two isolipidic (18% as fed) and isoproteic (42% as fed) diets were tested at the farm scale: a control diet without HI meal and an experimental diet with 11% HI meal replacing FM. At the end of the 25-week feeding trial, final body weight, specific growth rate, feed conversion rate, and hepatosomatic index were not affected by the diet. Gross morphology of the gastrointestinal tract and the liver was unchanged and showed no obvious signs of inflammation. High-throughput sequencing of 16S rRNA gene amplicons (MiSeq platform, Illumina) used to characterize the gut microbial community profile showed that Proteobacteria, Fusobacteria, and Firmicutes were the dominant phyla of the gut microbiota of gilthead seabream, regardless of diet. Dietary inclusion of HI meal altered the gut microbiota by significantly decreasing the abundance of Cetobacterium and increasing the relative abundance of the Oceanobacillus and Paenibacillus genera. Our results clearly indicate that the inclusion of HI meal as an alternative animal protein source positively affects the gut microbiota of seabream by increasing the abundance of beneficial genera, thereby improving gut health and maintaining growth performance of S. aurata from coastal farms.
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Affiliation(s)
- Simona Rimoldi
- Department of Biotechnology and Life Sciences, University of Insubria, Via J.H. Dunant, 3, 21100, Varese, Italy
| | - Ambra Rita Di Rosa
- Department of Veterinary Sciences, University of Messina, Messina, Italy.
| | - Marianna Oteri
- Department of Veterinary Sciences, University of Messina, Messina, Italy
| | - Biagina Chiofalo
- Department of Veterinary Sciences, University of Messina, Messina, Italy
| | - Imam Hasan
- Department of Biotechnology and Life Sciences, University of Insubria, Via J.H. Dunant, 3, 21100, Varese, Italy
| | - Marco Saroglia
- Department of Biotechnology and Life Sciences, University of Insubria, Via J.H. Dunant, 3, 21100, Varese, Italy
| | - Genciana Terova
- Department of Biotechnology and Life Sciences, University of Insubria, Via J.H. Dunant, 3, 21100, Varese, Italy.
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Tyczyńska M, Hunek G, Szczasny M, Brachet A, Januszewski J, Forma A, Portincasa P, Flieger J, Baj J. Supplementation of Micro- and Macronutrients-A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2024; 25:4916. [PMID: 38732128 PMCID: PMC11085010 DOI: 10.3390/ijms25094916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/28/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro- and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter.
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Affiliation(s)
- Magdalena Tyczyńska
- Department of Correct, Clinical and Imaging Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland;
| | - Gabriela Hunek
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Martyna Szczasny
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| | - Adam Brachet
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Jacek Januszewski
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Jolanta Flieger
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland;
| | - Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
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Song YF, Wang LJ, Luo Z, Hogstrand C, Lai XH, Zheng FF. Moderate replacement of fish oil with palmitic acid-stimulated mitochondrial fusion promotes β-oxidation by Mfn2 interacting with Cpt1α via its GTPase-domain. J Nutr Biochem 2024; 126:109559. [PMID: 38158094 DOI: 10.1016/j.jnutbio.2023.109559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 12/22/2023] [Accepted: 12/26/2023] [Indexed: 01/03/2024]
Abstract
The mitochondrial matrix serves as the principal locale for the process of fatty acids (FAs) β-oxidation. Preserving the integrity and homeostasis of mitochondria, which is accomplished through ongoing fusion and fission events, is of paramount importance for the effective execution of FAs β-oxidation. There has been no investigation to date into whether and how mitochondrial fusion directly enhances FAs β-oxidation. The underlying mechanism of a balanced FAs ratio favoring hepatic lipid homeostasis remains largely unclear. To address such gaps, the present study was conducted to investigate the mechanism through which a balanced dietary FAs ratio enhances hepatic FAs β-oxidation. The investigation specifically focused on the involvement of Mfn2-mediated mitochondrial fusion in the regulation of Cpt1α in this process. In the present study, the yellow catfish (Pelteobagrus fulvidraco), recognized as a model organism for lipid metabolism, were subjected to eight weeks of in vivo feeding with six distinct diets featuring varying FAs ratios. Additionally, in vitro experiments were conducted to inhibit Mfn2-mediated mitochondrial fusion in isolated hepatocytes, achieved through the transfection of hepatocytes with si-mfn2. Further, deletion mutants for both Mfn2 and Cpt1α were constructed to elucidate the critical regions responsible for the interactions between these two proteins within the system. The key findings were: (1) Substituting palmitic acid (PA) for fish oil (FO) proved to be enhanced in reducing hepatic lipid accumulation. This beneficial effect was primarily attributed to the activation of mitochondrial FAs β-oxidation; (2) The balanced replacement of PA stimulated Mfn2-mediated mitochondrial fusion by diminishing Mfn2 ubiquitination, thereby enhancing its protein retention within the mitochondria; (3) Mfn2-mediated mitochondrial fusion promoted FAs β-oxidation through direct interaction between Mfn2 and Cpt1α via its GTPase-domains, which is essential for the maintenance of Cpt1 activity. Notably, the present research results unveil a previously undisclosed mechanism wherein Mfn2-mediated mitochondrial fusion promotes FAs β-oxidation by directly augmenting the capacity for FA transport into mitochondria (MT), in addition to expanding the mitochondrial matrix. This underscores the pivotal role of mitochondrial fusion in preserving hepatic lipid homeostasis. The present results further confirm that these mechanisms are evolutionarily conserved, extending their relevance from fish to mammals.
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Affiliation(s)
- Yu-Feng Song
- Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, China.
| | - Ling-Jiao Wang
- Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, China
| | - Zhi Luo
- Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Christer Hogstrand
- Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, London, UK
| | - Xiao-Hong Lai
- Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, China
| | - Fei-Fei Zheng
- Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, China
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Samrit T, Osotprasit S, Chaiwichien A, Suksomboon P, Chansap S, Athipornchai A, Changklungmoa N, Kueakhai P. Cold-Pressed Sacha Inchi Oil: High in Omega-3 and Prevents Fat Accumulation in the Liver. Pharmaceuticals (Basel) 2024; 17:220. [PMID: 38399435 PMCID: PMC10892392 DOI: 10.3390/ph17020220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/01/2024] [Accepted: 02/04/2024] [Indexed: 02/25/2024] Open
Abstract
The ability of oil supplementation to inhibit various metabolic syndromes has been recognized. However, there are currently no studies determining the effects of oil supplements on healthy conditions. Plukenetia volubilis L., also known as Sacha inchi, is a seed rich in essential unsaturated fatty acids that improves metabolic syndrome diseases, such as obesity and nonalcoholic fatty liver. However, the health benefits and effects of Sacha inchi oil (SIO) supplementation remain unclear. This study aims to evaluate the chemical effects and properties of Sacha inchi oil. The results of the chemical compound analysis showed that Sacha inchi is an abundant source of ω-3 fatty acids, with a content of 44.73%, and exhibits scavenging activity of 240.53 ± 11.74 and 272.41 ± 6.95 µg Trolox/g, determined via DPPH and ABTS assays, respectively, while both olive and lard oils exhibited lower scavenging activities compared with Sacha inchi. Regarding liver histology, rats given Sacha inchi supplements showed lower TG accumulation and fat droplet distribution in the liver than those given lard supplements, with fat areas of approximately 14.19 ± 6.49% and 8.15 ± 2.40%, respectively. In conclusion, our findings suggest that Sacha inchi oil is a plant source of ω-3 fatty acids and antioxidants and does not induce fatty liver and pathology in the kidney, pancreas, and spleen. Therefore, it has the potential to be used as a dietary supplement to improve metabolic syndrome diseases.
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Affiliation(s)
- Tepparit Samrit
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
| | - Supawadee Osotprasit
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
| | - Athit Chaiwichien
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
| | - Phawiya Suksomboon
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
| | - Supanan Chansap
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
| | - Anan Athipornchai
- Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand;
| | - Narin Changklungmoa
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
| | - Pornanan Kueakhai
- Food Bioactive Compounds Research Unit, Faculty of Allied Health Sciences, Burapha University, Long-Hard Bangsaen Road, Saen Sook Sub-District, Mueang District, Chonburi 20131, Thailand; (T.S.); (S.O.); (A.C.); (P.S.); (S.C.); (N.C.)
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Das A, Tang YLM, Althumiri NA, Garcia-Larsen V, Schattenberg JM, Alqahtani SA. Fatty acid composition but not quantity is an important indicator of non-alcoholic fatty liver disease: a systematic review. Eur J Clin Nutr 2023; 77:1113-1129. [PMID: 37661229 DOI: 10.1038/s41430-023-01335-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND There is still paucity on the effects of dietary and supplemental fatty acid on non-alcoholic fatty liver disease (NAFLD). The aim of this review is to systematically review and summarise the effect of fatty acids intake on liver-related outcomes in adult patients with NAFLD. METHODS The review was conducted using Cochrane CENTRAL Library, Scopus, Embase, MEDLINE, PubMed, and Web of Science. A total of 2786 records were identified, and of these, 36 studies (31 were randomised control trials (RCTs), and 5 were case-control studies) were included. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS Of 36 articles, 79% of RCTs and 66% of case-control studies had a low risk of bias. Potential heterogeneity has been observed in assessment of liver-related outcomes. According to the RCTs, there was moderate evidence (3/6 studies) that a diet characterised by a high MUFA, PUFA and low SFA showed reduced liver fat and stiffness. The using of culinary fats that are high in MUFA (4/6 studies) reduces liver steatosis. n-3 PUFA supplementation in combination with a hypocaloric or heart healthy diet with a low SFA improved liver enzyme level (5/14 studies) and steatosis score (3/14 studies). CONCLUSIONS Effects on NAFLD parameters, including liver fat content (assessed via magnetic resonance imaging/spectroscopy), stiffness and steatosis score (assessed by ultrasonography), were primarily related to fatty acid composition independent of energy intake. Further investigation is needed to determine the mechanism of specific fatty acid on the accumulation of liver fat.
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Affiliation(s)
- Arpita Das
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
| | - Yu Lung Malcolm Tang
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | | | - Vanessa Garcia-Larsen
- Program in Human Nutrition, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Centre, Mainz, Germany
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
- Liver Transplantation Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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Zhu X, Cai J, Wang Y, Liu X, Chen X, Wang H, Wu Z, Bao W, Fan H, Wu S. A High-Fat Diet Increases the Characteristics of Gut Microbial Composition and the Intestinal Damage Associated with Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2023; 24:16733. [PMID: 38069055 PMCID: PMC10706137 DOI: 10.3390/ijms242316733] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/21/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing annually, and emerging evidence suggests that the gut microbiota plays a causative role in the development of NAFLD. However, the role of gut microbiota in the development of NAFLD remains unclear and warrants further investigation. Thus, C57BL/6J mice were fed a high-fat diet (HFD), and we found that the HFD significantly induced obesity and increased the accumulation of intrahepatic lipids, along with alterations in serum biochemical parameters. Moreover, it was observed that the HFD also impaired gut barrier integrity. It was revealed via 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Colidextribacter, Lachnospiraceae-NK4A136-group, Acetatifactor, and Erysipelatoclostridium. Meanwhile, it reduced the abundance of Faecalibaculum, Muribaculaceae, and Coriobacteriaceae-UCG-002. The predicted metabolic pathways suggest that HFD enhances the chemotaxis and functional activity of gut microbiota pathways associated with flagellar assembly, while also increasing the risk of intestinal pathogen colonization and inflammation. And the phosphotransferase system, streptomycin biosynthesis, and starch/sucrose metabolism exhibited decreases. These findings reveal the composition and predictive functions of the intestinal microbiome in NAFLD, further corroborating the association between gut microbiota and NAFLD while providing novel insights into its potential application in gut microbiome research for NAFLD patients.
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Affiliation(s)
- Xiaoyang Zhu
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
| | - Jiajia Cai
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China;
| | - Yifu Wang
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
| | - Xinyu Liu
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
| | - Xiaolei Chen
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
| | - Haifei Wang
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
| | - Zhengchang Wu
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
| | - Wenbin Bao
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China;
| | - Hairui Fan
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
- Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
| | - Shenglong Wu
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (X.Z.); (Y.W.); (X.L.); (X.C.); (H.W.); (Z.W.); (W.B.)
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China;
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10
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Vesković M, Šutulović N, Hrnčić D, Stanojlović O, Macut D, Mladenović D. The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease-The Transition from an Adipocentric to Liver-Centric Approach. Curr Issues Mol Biol 2023; 45:9084-9102. [PMID: 37998747 PMCID: PMC10670061 DOI: 10.3390/cimb45110570] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/01/2023] [Accepted: 11/09/2023] [Indexed: 11/25/2023] Open
Abstract
The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.
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Affiliation(s)
- Milena Vesković
- Institute of Pathophysiology “Ljubodrag Buba Mihailovic”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | - Nikola Šutulović
- Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (N.Š.); (D.H.); (O.S.)
| | - Dragan Hrnčić
- Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (N.Š.); (D.H.); (O.S.)
| | - Olivera Stanojlović
- Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (N.Š.); (D.H.); (O.S.)
| | - Djuro Macut
- Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | - Dušan Mladenović
- Institute of Pathophysiology “Ljubodrag Buba Mihailovic”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
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11
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Hwang G, Seo H, Park JC. Copine7 deficiency leads to hepatic fat accumulation via mitochondrial dysfunction. Heliyon 2023; 9:e21676. [PMID: 37954344 PMCID: PMC10637907 DOI: 10.1016/j.heliyon.2023.e21676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/25/2023] [Accepted: 10/25/2023] [Indexed: 11/14/2023] Open
Abstract
Objective Mitochondrial dysfunction affects hepatic lipid homeostasis and promotes ROS generation. Copine7 (CPNE7) belongs to the ubiquitous copine family of calcium-dependent phospholipid binding proteins. CPNE7 has a high calcium ion binding affinity and the capacity to scavenge reactive oxygen species (ROS). A recent study reported that abnormalities in fatty acid and lipid metabolism were linked to the gene variant of CPNE7. Therefore, the purpose of this study is to examine the role of Cpne7 in hepatic lipid metabolism based on mitochondrial function. Methods Lipid metabolism, mitochondrial function, and ROS production were investigated in high-fat diet (HFD)-fed Cpne7-/- mice and H2O2-damaged HepG2 hepatocytes following CPNE7 silencing or overexpression. Results Cpne7 deficiency promoted severe hepatic steatosis in the HFD-induced NAFLD model. More importantly, mitochondrial dysfunction was observed along with an imbalance of mitochondrial dynamics in the livers of HFD-fed Cpne7-/-mice, resulting in high ROS levels. Similarly, CPNE7-silenced HepG2 hepatocytes showed high ROS levels, mitochondrial dysfunction, and increased lipid contents. On the contrary, CPNE7-overexpressed HepG2 cells showed low ROS levels, enhanced mitochondrial function and decreased lipid contents under H2O2-induced oxidative stress. Conclusions In the liver, Cpne7 deficiency causes excessive ROS formation and mitochondrial dysfunction, which aggravates lipid metabolism abnormalities. These findings provide evidence that Cpne7 deficiency contributes to the pathogenesis of NAFLD, suggesting Cpne7 as a novel therapeutic target for NAFLD.
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Affiliation(s)
- Geumbit Hwang
- Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology-Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
- Regenerative Dental Medicine R & D Center, HysensBio, Co., Ltd., 10 Dwitgol-ro, Gwacheon-si, Gyeonggi-do, Republic of Korea
| | - Hyejin Seo
- Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology-Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
| | - Joo-Cheol Park
- Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology-Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
- Regenerative Dental Medicine R & D Center, HysensBio, Co., Ltd., 10 Dwitgol-ro, Gwacheon-si, Gyeonggi-do, Republic of Korea
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12
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Lei P, Lü J, Yao T, Zhang P, Chai X, Wang Y, Jiang M. Verbascoside exerts an anti-atherosclerotic effect by regulating liver glycerophospholipid metabolism. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.03.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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13
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Lee R, Lee WY, Park HJ. Effects of Melatonin on Liver of D-Galactose-Induced Aged Mouse Model. Curr Issues Mol Biol 2023; 45:8412-8426. [PMID: 37886973 PMCID: PMC10604925 DOI: 10.3390/cimb45100530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 10/28/2023] Open
Abstract
Melatonin, a hormone secreted by the pineal gland of vertebrates, regulates sleep, blood pressure, and circadian and seasonal rhythms, and acts as an antioxidant and anti-inflammatory agent. We investigated the protective effects of melatonin against markers of D-galactose (D-Gal)-induced hepatocellular aging, including liver inflammation, hepatocyte structural damage, and non-alcoholic fatty liver. Mice were divided into four groups: phosphate-buffered saline (PBS, control), D-Gal (200 mg/kg/day), melatonin (20 mg/kg), and D-Gal (200 mg/kg) and melatonin (20 mg) cotreatment. The treatments were administered once daily for eight consecutive weeks. Melatonin treatment alleviated D-Gal-induced hepatocyte impairment. The AST level was significantly increased in the D-Gal-treated groups compared to that in the control group, while the ALT level was decreased compared to the melatonin and D-Gal cotreated group. Inflammatory genes, such as IL1-β, NF-κB, IL-6, TNFα, and iNOS, were significantly increased in the D-Gal aging model, whereas the expression levels of these genes were low in the D-Gal and melatonin cotreated group. Interestingly, the expression levels of hepatic steatosis-related genes, such as LXRα, C/EBPα, PPARα, ACC, ACOX1, and CPT-1, were markedly decreased in the D-Gal and melatonin cotreated group. These results suggest that melatonin suppresses hepatic steatosis and inflammation in a mouse model of D-Gal-induced aging.
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Affiliation(s)
- Ran Lee
- Department of Livestock, Korea National University of Agriculture and Fisheries, Jeonju 54874, Republic of Korea; (R.L.); (W.-Y.L.)
- Department of Animal Biotechnology, College of Life Science, Sangji University, Wonju-si 26339, Republic of Korea
| | - Won-Yong Lee
- Department of Livestock, Korea National University of Agriculture and Fisheries, Jeonju 54874, Republic of Korea; (R.L.); (W.-Y.L.)
| | - Hyun-Jung Park
- Department of Animal Biotechnology, College of Life Science, Sangji University, Wonju-si 26339, Republic of Korea
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14
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Mao Z, Ma X, Jing Y, Shen M, Ma X, Zhu J, Liu H, Zhang G, Chen F. Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress. Cell Death Dis 2023; 14:584. [PMID: 37660122 PMCID: PMC10475044 DOI: 10.1038/s41419-023-06095-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 08/06/2023] [Accepted: 08/21/2023] [Indexed: 09/04/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease characterized by lipid accumulation and endoplasmic reticulum (ER) stress, while effective therapies targeting the specific characteristics of NAFLD are limited. Ufmylation is a newly found post-translational modification process that involves the attachment of the Ubiquitin-fold modifier 1 (UFM1) protein to its substrates via ufmylation modification system. Ufmylation regulates ER stress via modifying UFM1 binding protein 1 (UFBP1), suggesting a potential role for ufmylation in NAFLD pathogenesis. However, the precise role of ufmylation in NAFLD remains unclear. Herein, we aim to elucidate the impact of ufmylation on UFBP1 in NAFLD and explore the underlying mechanisms involved. We observed increased expression of UFM1-conjugated proteins and ufmylation modification system components in livers with steatosis derived from NAFLD patients and NAFLD models. Upregulation of ufmylation on hepatic proteins appeared to be an adaptive response to hepatic ER stress in NAFLD. In vitro, knocking down UFBP1 resulted in increased lipid accumulation and lipogenesis in hepatocytes treated with free fatty acids (FFA), which could be rescued by wild-type UFBP1 (WT UFBP1) but not by a mutant form of UFBP1 lacking the main ufmylation site lys267 (UFBP1 K267R). In vivo, ufmylation on UFBP1 ameliorated obesity, hepatic steatosis, hepatic lipogenesis, dyslipidemia, insulin resistance and liver damage in mice with NAFLD induced by a high fat diet (HFD). We also demonstrated that the downregulation of UFBP1 induced ER stress, whereas the reintroduction or overexpression of UFBP1 alleviated ER stress in a manner dependent on ufmylation in NAFLD. This mechanism could be responsible for the amelioration of aberrant hepatic lipogenesis and insulin resistance in NAFLD. Our data reveal a protective role of ufmylation on UFBP1 against NAFLD and offer a specific target for NAFLD treatment.
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Affiliation(s)
- Ziming Mao
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China
| | - Xiaowen Ma
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China
| | - Yu Jing
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China
| | - Minyan Shen
- School of Graduate, Bengbu Medical College, Bengbu, Anhui, 233030, China
| | - Xirui Ma
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China
| | - Jing Zhu
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China
| | - Huifang Liu
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China.
| | - Guangya Zhang
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200233, China.
| | - Fengling Chen
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China.
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15
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Wang H, Wang L, Tian C, Rajput SA, Qi D. Effects of Methyl Sulfonyl Methane and Selenium Yeast on Fatty Liver Syndrome in Laying Hens and Their Biological Mechanisms. Animals (Basel) 2023; 13:2466. [PMID: 37570275 PMCID: PMC10416963 DOI: 10.3390/ani13152466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/27/2023] [Accepted: 07/29/2023] [Indexed: 08/13/2023] Open
Abstract
The purpose of this study was to explore the effects of MSM and Se-Y on FLS in laying hens during the late peak laying period and the underlying biological mechanisms. Therefore 240 55-week-old Jing-fen No. 6 laying hens were randomly divided into five groups, with eight replicates in each group and six laying hens in each replicate. The hens were fed a basal diet (Control) and diets supplemented with 350 and 700 mg/kg MSM and 25 and 50 mg/kg Se-Y, respectively, for four weeks. The results showed that MSM and Se-Y had no significant effects on the performance of laying hens. With the increasing dosage of MSM and Se-Y, the symptoms of liver steatosis in laying hens were reduced, and MSM and Se-Y could significantly reduce the content of malondialdehyde (MDA) in serum and liver (p < 0.05) and increase the contents of total superoxide dismutase (T-SOD) and glutathione peroxidase (GPX) in serum and liver (p < 0.05). The RNA-seq results showed that 700 mg/kg MSM significantly downregulated the expression levels of the ATP5I, ATP5G1, CYCS, and UQCRQ genes in the liver, and 50 mg/kg Se-Y significantly downregulated the expression levels of MAPK10, SRC, BMP2, and FGF9 genes in the liver. In conclusion, dietary supplementation with MSM and Se-Y can effectively reduce the FLS of laying hens in the late peak laying period and increase their antioxidant capacity. The underlying biological mechanism may be related to the downregulation of genes involved in liver oxidative phosphorylation and inflammation-related pathways.
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Affiliation(s)
- Huanbin Wang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (H.W.); (L.W.); (C.T.)
| | - Lingfeng Wang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (H.W.); (L.W.); (C.T.)
| | - Changyu Tian
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (H.W.); (L.W.); (C.T.)
| | - Shahid Ali Rajput
- Faculty of Veterinary and Animal Science, Muhammad Nawaz Shareef University of Agriculture, Multan 60000, Pakistan;
| | - Desheng Qi
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (H.W.); (L.W.); (C.T.)
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16
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Fang X, Song J, Zhou K, Zi X, Sun B, Bao H, Li L. Molecular Mechanism Pathways of Natural Compounds for the Treatment of Non-Alcoholic Fatty Liver Disease. Molecules 2023; 28:5645. [PMID: 37570615 PMCID: PMC10419790 DOI: 10.3390/molecules28155645] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 07/21/2023] [Accepted: 07/21/2023] [Indexed: 08/13/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its incidence continues to increase each year. Yet, there is still no definitive drug that can stop its development. This review focuses mainly on lipotoxicity, oxidative stress, inflammation, and intestinal flora dysbiosis to understand NAFLD's pathogenesis. In this review, we used NCBI's PubMed database for retrieval, integrating in vivo and in vitro experiments to reveal the therapeutic effects of natural compounds on NAFLD. We also reviewed the mechanisms by which the results of these experiments suggest that these compounds can protect the liver from damage by modulating inflammation, reducing oxidative stress, decreasing insulin resistance and lipid accumulation in the liver, and interacting with the intestinal microflora. The natural compounds discussed in these papers target a variety of pathways, such as the AMPK pathway and the TGF-β pathway, and have significant therapeutic effects. This review aims to provide new possible therapeutic lead compounds and references for the development of novel medications and the clinical treatment of NAFLD. It offers fresh perspectives on the development of natural compounds in preventing and treating NAFLD.
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Affiliation(s)
| | | | | | | | | | | | - Lijing Li
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (X.F.)
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17
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Pan ZS, Chen YL, Tang KJ, Liu ZZ, Liang JL, Guan YH, Xin XY, Liu CH, Shen CP. Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders. Exp Ther Med 2023; 26:320. [PMID: 37273757 PMCID: PMC10236048 DOI: 10.3892/etm.2023.12019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 03/01/2023] [Indexed: 06/06/2023] Open
Abstract
Pachymic acid (Pac), a major bioactive constituent of Poria cocos, is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver-specific SIRT6-deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA-induced lipid deposition in MPHs in a dose-dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA-incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA-induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA-induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis.
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Affiliation(s)
- Zhi-Sen Pan
- Department of Traditional Chinese Medicine, The First People's Hospital of Kashgar Prefecture, Kashgar, Xinjiang Uyghur Autonomous Region 844000, P.R. China
- Department of Endocrinology, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Yan-Ling Chen
- Department of Endocrinology, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Kai-Jia Tang
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Zhang-Zhou Liu
- Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Jia-Li Liang
- Department of Endocrinology, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Yan-Hao Guan
- Department of Endocrinology, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Xiao-Yi Xin
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China
| | - Chang-Hui Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Chuang-Peng Shen
- Department of Traditional Chinese Medicine, The First People's Hospital of Kashgar Prefecture, Kashgar, Xinjiang Uyghur Autonomous Region 844000, P.R. China
- Department of Endocrinology, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
- Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China
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18
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Zeng W, Xu X, Xu F, Zhu F, Li Y, Ma J. Exploring Key Genes with Diagnostic Value for Nonalcoholic Steatohepatitis Based on Bioinformatics Analysis. ACS OMEGA 2023; 8:20959-20967. [PMID: 37323410 PMCID: PMC10268261 DOI: 10.1021/acsomega.3c01709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 04/27/2023] [Indexed: 06/17/2023]
Abstract
We aimed to screen specific genes in liver tissue samples of patients with nonalcoholic steatohepatitis (NASH) with clinical diagnostic value based on bioinformatics analysis. The datasets of liver tissue samples from healthy individuals and NASH patients were retrieved for consistency cluster analysis to obtain the NASH sample typing, followed by verification of the diagnostic value of sample genotyping-specific genes. All samples were subjected to logistic regression analysis, followed by the establishment of the risk model, and then, the diagnostic value was determined by receiver operating characteristic curve analysis. NASH samples could be divided into cluster 1, cluster 2, and cluster 3, which could predict the nonalcoholic fatty liver disease activity score of patients. A total of 162 sample genotyping-specific genes were extracted from patient clinical parameters, and the top 20 core genes in the protein interaction network were obtained for logistic regression analysis. Five sample genotyping-specific genes (WD repeat and HMG-box DNA-binding protein 1 [WDHD1], GINS complex subunit 2 [GINS2], replication factor C subunit 3 (RFC3), secreted phosphoprotein 1 [SPP1], and spleen tyrosine kinase [SYK]) were extracted to construct the risk models with high diagnostic value in NASH. Compared with the low-risk group, the high-risk group of the model showed increased lipoproduction and decreased lipolysis and lipid β oxidation. The risk models based on WDHD1, GINS2, RFC3, SPP1, and SYK have high diagnostic value in NASH, and this risk model is closely related to lipid metabolism pathways.
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Affiliation(s)
- Wenchun Zeng
- Department
of Gastroenterology, The First People’s
Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, P. R. China
| | - Xiangwei Xu
- Department
of Pharmacy, The First People’s Hospital
of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, P. R. China
| | - Fang Xu
- Department
of Gastroenterology, The First People’s
Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, P. R. China
| | - Fang Zhu
- Department
of Gastroenterology, The First People’s
Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, P. R. China
| | - Yuecui Li
- Department
of Infectious Liver Disease, The First People’s
Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, P. R. China
| | - Ji Ma
- Department
of Gastroenterology, The First People’s
Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, P. R. China
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19
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Zarantoniello M, de Oliveira AA, Sahin T, Freddi L, Torregiani M, Tucciarone I, Chemello G, Cardinaletti G, Gatto E, Parisi G, Bertolucci C, Riolo P, Nartea A, Gioacchini G, Olivotto I. Enhancing Rearing of European Seabass ( Dicentrarchus labrax) in Aquaponic Systems: Investigating the Effects of Enriched Black Soldier Fly ( Hermetia illucens) Prepupae Meal on Fish Welfare and Quality Traits. Animals (Basel) 2023; 13:1921. [PMID: 37370431 DOI: 10.3390/ani13121921] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Within the modern aquaculture goals, the present study aimed to couple sustainable aquafeed formulation and culturing systems. Two experimental diets characterized by 3 and 20% of fish meal replacement with full-fat spirulina-enriched black soldier fly (Hermetia illucens) prepupae meal (HPM3 and HPM20, respectively) were tested on European seabass (Dicentrarchus labrax) juveniles during a 90-day feeding trial performed in aquaponic systems. The experimental diets ensured 100% survival and proper zootechnical performance. No behavioral alterations were evidenced in fish. Histological and molecular analyses did not reveal structural alterations and signs of inflammation at the intestinal level, highlighting the beneficial role on gut health of bioactive molecules typical of HPM or derived from the enriching procedure of insects' growth substrate with spirulina. Considering the quality traits, the tested experimental diets did not negatively alter the fillet's fatty acid profile and did not compromise the fillet's physical features. In addition, the results highlighted a possible role of spirulina-enriched HPM in preserving the fillet from lipid oxidation. Taken together, these results corroborate the use of sustainable ingredients (spirulina-enriched HPM) in aquaponic systems for euryhaline fish rearing.
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Affiliation(s)
- Matteo Zarantoniello
- Department of Life and Environmental Sciences, Marche Polytechnic University, 60131 Ancona, Italy
| | - Adriana Alves de Oliveira
- CIMAR/CIIMAR Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matoshinos, Portugal
| | - Tolga Sahin
- Department of Aquaculture, Marine Sciences and Technology Faculty, Çanakkale Onsekiz Mart University, 17000 Çanakkale, Turkey
| | - Lorenzo Freddi
- Mj Energy srl Società Agricola, Contrada SS. Crocifisso, 22, 62010 Treia, Italy
| | - Matteo Torregiani
- Department of Life and Environmental Sciences, Marche Polytechnic University, 60131 Ancona, Italy
| | - Isabella Tucciarone
- Department of Agriculture, Food, Environment and Forestry, University of Florence, 50144 Firenze, Italy
| | - Giulia Chemello
- Department of Life and Environmental Sciences, Marche Polytechnic University, 60131 Ancona, Italy
| | - Gloriana Cardinaletti
- Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, 33100 Udine, Italy
| | - Elia Gatto
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44100 Ferrara, Italy
- Department of Life Sciences and Biotechnology, University of Ferrara, 44100 Ferrara, Italy
| | - Giuliana Parisi
- Department of Agriculture, Food, Environment and Forestry, University of Florence, 50144 Firenze, Italy
| | - Cristiano Bertolucci
- Department of Life Sciences and Biotechnology, University of Ferrara, 44100 Ferrara, Italy
| | - Paola Riolo
- Department of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
| | - Ancuta Nartea
- Department of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
| | - Giorgia Gioacchini
- Department of Life and Environmental Sciences, Marche Polytechnic University, 60131 Ancona, Italy
| | - Ike Olivotto
- Department of Life and Environmental Sciences, Marche Polytechnic University, 60131 Ancona, Italy
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20
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Zou YY, Tang XB, Chen ZL, Liu B, Zheng L, Song MY, Xiao Q, Zhou ZQ, Peng XY, Tang CF. Exercise intervention improves mitochondrial quality in non-alcoholic fatty liver disease zebrafish. Front Endocrinol (Lausanne) 2023; 14:1162485. [PMID: 37284220 PMCID: PMC10239848 DOI: 10.3389/fendo.2023.1162485] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 05/09/2023] [Indexed: 06/08/2023] Open
Abstract
Introduction Recent reports indicate that mitochondrial quality decreases during non-alcoholic fatty liver disease (NAFLD) progression, and targeting the mitochondria may be a possible treatment for NAFLD. Exercise can effectively slow NAFLD progression or treat NAFLD. However, the effect of exercise on mitochondrial quality in NAFLD has not yet been established. Methods In the present study, we fed zebrafish a high-fat diet to model NAFLD, and subjected the zebrafish to swimming exercise. Results After 12 weeks, swimming exercise significantly reduced high-fat diet-induced liver injury, and reduced inflammation and fibrosis markers. Swimming exercise improved mitochondrial morphology and dynamics, inducing upregulation of optic atrophy 1(OPA1), dynamin related protein 1 (DRP1), and mitofusin 2 (MFN2) protein expression. Swimming exercise also activated mitochondrial biogenesis via the sirtuin 1 (SIRT1)/ AMP-activated protein kinase (AMPK)/ PPARgamma coactivator 1 alpha (PGC1α) pathway, and improved the mRNA expression of genes related to mitochondrial fatty acid oxidation and oxidative phosphorylation. Furthermore, we find that mitophagy was suppressed in NAFLD zebrafish liver with the decreased numbers of mitophagosomes, the inhibition of PTEN-induced kinase 1 (PINK1) - parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway and upregulation of sequestosome 1 (P62) expression. Notably, swimming exercise partially recovered number of mitophagosomes, which was associated with upregulated PARKIN expression and decreased p62 expression. Discussion These results demonstrate that swimming exercise could alleviate the effects of NAFLD on the mitochondria, suggesting that exercise may be beneficial for treating NAFLD.
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Affiliation(s)
| | | | | | | | | | | | | | - Zuo-Qiong Zhou
- *Correspondence: Chang-Fa Tang, ; Zuo-Qiong Zhou, ; Xi-Yang Peng,
| | - Xi-Yang Peng
- *Correspondence: Chang-Fa Tang, ; Zuo-Qiong Zhou, ; Xi-Yang Peng,
| | - Chang-Fa Tang
- *Correspondence: Chang-Fa Tang, ; Zuo-Qiong Zhou, ; Xi-Yang Peng,
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21
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Peloso A, Tihy M, Moeckli B, Rubbia-Brandt L, Toso C. Clearing Steatosis Prior to Liver Surgery for Colorectal Metastasis: A Narrative Review and Case Illustration. Nutrients 2022; 14:5340. [PMID: 36558499 PMCID: PMC9785595 DOI: 10.3390/nu14245340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/26/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
Over recent years, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in the developed world, accounting for 20% to 46% of liver abnormalities. Steatosis is the hallmark of NAFLD and is recognized as an important risk factor for complication and death after general surgery, even more so after liver resection. Similarly, liver steatosis also impacts the safety of live liver donation and transplantation. We aim to review surgical outcomes after liver resection for colorectal metastases in patients with steatosis and discuss the most common pre-operative strategies to reduce steatosis. Finally, as illustration, we report the favorable effect of a low-caloric, hyper-protein diet during a two-stage liver resection for colorectal metastases in a patient with severe steatosis.
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Affiliation(s)
- Andrea Peloso
- Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland
| | - Matthieu Tihy
- Department of Pathology and Immunology, University of Geneva, 1205 Geneva, Switzerland
- Division of Clinical Pathology, Geneva University Hospital, 1205 Geneva, Switzerland
| | - Beat Moeckli
- Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland
| | - Laura Rubbia-Brandt
- Department of Pathology and Immunology, University of Geneva, 1205 Geneva, Switzerland
- Division of Clinical Pathology, Geneva University Hospital, 1205 Geneva, Switzerland
| | - Christian Toso
- Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland
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22
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Meng Q, Sun H, Wu S, Familiari G, Relucenti M, Aschner M, Li X, Chen R. Epstein-Barr Virus-Encoded MicroRNA-BART18-3p Promotes Colorectal Cancer Progression by Targeting De Novo Lipogenesis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2202116. [PMID: 36307872 PMCID: PMC9762317 DOI: 10.1002/advs.202202116] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 07/29/2022] [Indexed: 05/14/2023]
Abstract
The Epstein-Barr virus (EBV) genome encodes a cluster of 22 viral microRNAs, called miR-BamHI-A rightward transcripts (miR-BARTs), which are shown to promote the development of cancer. Here, this study reports that EBV-miR-BART18-3p is highly expressed in colorectal cancer (CRC) and is closely associated with the pathological and advanced clinical stages of CRC. Ectopic expression of EBV-miR-BART18-3p leads to increased migration and invasion capacities of CRC cells in vitro and causes tumor metastasis in vivo. Mechanistically, EBV-miR-BART18-3p activates the hypoxia inducible factor 1 subunit alpha/lactate dehydrogenase A axis by targeting Sirtuin, which promotes lactate accumulation and acetyl-CoA production in CRC cells under hypoxic condition. Increased acetyl-CoA utilization subsequently leads to histone acetylation of fatty acid synthase and fatty acid synthase-dependent fat synthesis, which in turn drives de novo lipogenesis. The oncogenic role of EBV-miR-BART18-3p is confirmed in the patient-derived tumor xenograft mouse model. Altogether, the findings define a novel mechanism of EBV-miR-BART18-3p in CRC development through the lipogenesis pathway and provide a potential clinical intervention target for CRC.
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Affiliation(s)
- Qingtao Meng
- Beijing Key Laboratory of Environmental Toxicology, School of Public HealthCapital Medical UniversityBeijing100069P. R. China
- Department of OncologyCapital Medical UniversityBeijing100069P. R. China
| | - Hao Sun
- Department of Occupational HealthSchool of Public HealthShanxi Medical UniversityTaiyuan030001China
- Key Laboratory of Environmental Medicine EngineeringMinistry of EducationSchool of Public HealthSoutheast UniversityNanjing210009P. R. China
| | - Shenshen Wu
- Beijing Key Laboratory of Environmental Toxicology, School of Public HealthCapital Medical UniversityBeijing100069P. R. China
| | - Giuseppe Familiari
- Laboratory of Electron Microscopy “Pietro Motta”SAIMLAL DepartmentFaculty of Pharmacy and MedicineSapienza University of Romevia Alfonso Borelli 50Rome00161Italy
| | - Michela Relucenti
- Laboratory of Electron Microscopy “Pietro Motta”SAIMLAL DepartmentFaculty of Pharmacy and MedicineSapienza University of Romevia Alfonso Borelli 50Rome00161Italy
| | - Michael Aschner
- Department of Molecular PharmacologyAlbert Einstein College of MedicineForchheimer 209, 1300 Morris Park AvenueBronxNY10461USA
| | - Xiaobo Li
- Beijing Key Laboratory of Environmental Toxicology, School of Public HealthCapital Medical UniversityBeijing100069P. R. China
- Key Laboratory of Environmental Medicine EngineeringMinistry of EducationSchool of Public HealthSoutheast UniversityNanjing210009P. R. China
| | - Rui Chen
- Beijing Key Laboratory of Environmental Toxicology, School of Public HealthCapital Medical UniversityBeijing100069P. R. China
- Department of OncologyCapital Medical UniversityBeijing100069P. R. China
- Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing100069P. R. China
- Institute for Chemical CarcinogenesisGuangzhou Medical UniversityGuangzhou511436P. R. China
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23
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Lactobacillus sakei MJM60958 as a Potential Probiotic Alleviated Non-Alcoholic Fatty Liver Disease in Mice Fed a High-Fat Diet by Modulating Lipid Metabolism, Inflammation, and Gut Microbiota. Int J Mol Sci 2022; 23:ijms232113436. [PMID: 36362221 PMCID: PMC9658623 DOI: 10.3390/ijms232113436] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/28/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease with a rapidly increasing number of cases worldwide. This study aimed to evaluate the effects of Lactobacillus sakei MJM60958 (MJM60958) on NAFLD in vitro and in vivo. In in vitro tests, MJM60958 significantly inhibited lipid accumulation by 46.79% in HepG2 cells stimulated with oleic acid and cholesterol (OA-C). Moreover, MJM60958 showed safe and probiotic characteristics in vitro. In the animal study, MJM60958 administration in a high-fat diet-induced NAFLD mouse model significantly reduced body weight and liver weight, and controlled aspartate aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), urea nitrogen (BUN), and uric acid (UA) levels in the blood, which are features of NAFLD. Further, treatment with MJM60958 also reduced steatosis scores in liver tissues, serum leptin and interleukin, and increased serum adiponectin content. Moreover, administration of MJM60958 resulted in a significantly decreased expression of some genes and proteins which are related to lipid accumulation, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1 (SREBP-1), and also upregulated genes and protein expression of lipid oxidation such as peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1a (CPT1A). Administration of MJM60958 increased the relative abundance of specific microbial taxa such as Verrucomicrobia, which are abundant in non-NAFLD mice, and reduced Firmicutes, which are a major group in NAFLD mice. MJM60958 affected the modulation of gut microbiota and altered the strain profile of short-chain fatty acids (SCFAs) production in the cecum by reduced lactic acid and enhanced acetic acid production. Overall, MJM60958 showed potential as a probiotic that can prevent and treat NAFLD.
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24
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Pakhomova IG, Knorring GY. Non-alcoholic fatty liver disease and cardiovascular pathology: features of patient management on a clinical example. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:290-297. [DOI: 10.31146/1682-8658-ecg-205-9-290-297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is recognized as an interdisciplinary problem at the intersection of therapy, gastroenterology and endocrinology. In recent years, there has been a significant increase in interest in NAFLD as an accomplice of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). The article discusses the mechanisms of NAFLD in the development and progression of cardiovascular diseases depending on risk factors and comorbidity, including a clinical case. The proven clear association of NAFLD with obesity, DM 2, CVD suggests that these comorbid diseases are interdependent in their natural course. Pathogenetically substantiated management of NAFLD can positively influence the course of comorbid conditions. The role of ursodeoxycholic acid drugs in the treatment of NAFLD and the effect of this therapy on the course of associated diseases and conditions are discussed.
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Affiliation(s)
- I. G. Pakhomova
- Almazov National Medical Research Centre of the Ministry of Health of the Russian Federation
| | - G. Yu. Knorring
- Moscow State University of Medicine and Dentistry named after A. I. Evdakimov
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25
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Lucena TLC, Batista KS, Pinheiro RO, Cavalcante HC, Gomes JADS, da Silva LA, Lins PP, Ferreira FS, Lima RF, Lima MDS, Aquino JDS. Nutritional Characterization, Antioxidant, and Lipid-Lowering Effects of Yellow Mombin ( Spondias mombin) Supplemented to Rats Fed a High-Fat Diet. Foods 2022; 11:foods11193064. [PMID: 36230142 PMCID: PMC9563763 DOI: 10.3390/foods11193064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/26/2022] [Accepted: 09/28/2022] [Indexed: 11/26/2022] Open
Abstract
The aim of this study was to evaluate the effects of supplementing yellow mombin (YM) on the oxidative, somatic, and lipid parameters in rats fed a high-fat diet. A total of 24 adult Wistar rats were randomized into three groups: normal-fat diet (NF), high-fat diet (HF), and high-fat diet with YM supplementation (HFYM). Diets were administered for four weeks, and YM (400 mg/kg) was supplemented via gavage in the last two weeks of the experiment. After the four-week period, the somatic, serum biochemical, and liver oxidative parameters were evaluated. YM has a high antioxidant activity and significant amounts of phenolic compounds, carotenoids, vitamin C, dietary fibre, and minerals. The HFYM group had the lowest body weight (18.75%), body mass index (17.74%), and adiposity (31.63%) compared with the HF group. YM supplementation reduced low-density lipoprotein by 43.05% and increased high-density lipoprotein by 25.73%, but did not improve the triglyceride levels in the serum. YM treatment improved glucose tolerance and lipid peroxidation, and also enhanced the antioxidant capacity, superoxide dismutase, and glutathione peroxidase activities in the liver. These results indicate the lipid-lowering property and potential antioxidant activity of YM against liver oxidative damage caused by a high-fat diet intake, which may be associated with the bioactive compounds present in this fruit.
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Affiliation(s)
- Tatiana Luiza Costa Lucena
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Kamila Sabino Batista
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Post Graduate Program in Nutrition Sciences, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Rafael Oliveira Pinheiro
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Post Graduate Program in Nutrition Sciences, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Hassler Clementino Cavalcante
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Post Graduate Program in Nutrition Sciences, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Jéssyca Alencar de Sousa Gomes
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Laiane Alves da Silva
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Priscilla Paulo Lins
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Fabrícia Souza Ferreira
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Post Graduate Program in Food Science and Technology, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
| | - Rafael Ferreira Lima
- Postgraduate Program in Agroindustrial Systems, Campus Pombal, Federal University of Campina Grande (UFCG), Pombal 58840-000, Paraíba, Brazil
| | - Marcos dos Santos Lima
- Post Graduate Program in Food Science and Technology, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Department of Food Technology, Federal Institute of Sertão Pernambucano (IF SertãoPE), Petrolina 56316-686, Pernambuco, Brazil
| | - Jailane de Souza Aquino
- Experimental Nutrition Laboratory—LANEX, Department of Nutrition, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Post Graduate Program in Nutrition Sciences, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Post Graduate Program in Food Science and Technology, Federal University of Paraíba (UFPB), Campus I, João Pessoa 58051-900, Paraíba, Brazil
- Correspondence:
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26
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Ivashkin VT, Maevskaya MV, Zharkova MS, Kotovskaya YV, Tkacheva ON, Troshina EA, Shestakova MV, Maev IV, Breder VV, Gheivandova NI, Doshchitsin VL, Dudinskaya EN, Ershova EV, Kodzoeva KB, Komshilova KA, Korochanskaya NV, Mayorov AY, Mishina EE, Nadinskaya MY, Nikitin IG, Pogosova NV, Tarzimanova AI, Shamkhalova MS. Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2022; 32:104-140. [DOI: 10.22416/1382-4376-2022-32-4-104-140] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Aim:present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points.Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion.Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.
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Affiliation(s)
| | | | | | - Yu. V. Kotovskaya
- Russian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical University
| | - O. N. Tkacheva
- Russian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical University
| | | | | | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - V. V. Breder
- Blokhin National Medical Research Center of Oncology
| | | | | | - E. N. Dudinskaya
- Russian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical University
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27
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Safari Hasanabad M, Ghorbanlou M, Masoumi R, Shokri S, Rostami B, Mirzaei-Alamouti H, Catt S, Green MP, Nejatbakhsh R. Effects of dietary supplementation of different oils and conjugated linoleic acid on the reproductive and metabolic aspects of male mice. Andrologia 2022; 54:e14598. [PMID: 36161725 DOI: 10.1111/and.14598] [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: 10/20/2021] [Revised: 08/22/2022] [Accepted: 09/07/2022] [Indexed: 11/30/2022] Open
Abstract
The present study was carried out to examine first, if diets enriched with 320 g of the base diet with common dietary oils including fish oil, olive oil, hydrogenated sunflower seed (H-SFS) oil, flaxseed oil and sunflower seed oil (SFS) could induce weight gain and alter reproductive and metabolic characteristics of male mice. Second, whether the addition of conjugated linoleic acid (CLA, 10% of the diet) could ameliorate any negative effects. In this cross-sectional study, 90 four-week-old male NMRI mice were used in two consecutive experiments. A high level of dietary oils negatively affected some reproductive and metabolic characteristics of male mice (p < 0.05), specifically, sunflower seed oil enrichment resulted in higher HDL levels and apoptosis of germinal epithelial cells. An olive oil-enriched diet caused an increase in plasma triglyceride concentrations and germinal cell apoptosis, as well as a decrease in sperm concentration and perturbed spermatogenesis. When CLA was fed in conjunction with dietary oils it successfully mitigated some of the negative reproductive and metabolic characteristics. We conclude that male reproductive processes are affected by high dietary oils, even before signs of obesity are evident. Inclusion of dietary CLA may provide some benefit to offset negative effects, although further studies are required.
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Affiliation(s)
| | - Mehrdad Ghorbanlou
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Masoumi
- Department of Animal Science, Faculty of Agriculture, University of Zanjan, Zanjan, Iran
| | - Saeed Shokri
- School of Rural Health, Faculty of Medicine and Health, University of Sydney, Dubbo, New South Wales, Australia
| | - Behnam Rostami
- Department of Animal Science, Faculty of Agriculture, University of Zanjan, Zanjan, Iran
| | | | - Sally Catt
- Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
| | - Mark P Green
- School of BioSciences, University of Melbourne, Parkville, Melbourne, Victoria, Australia
| | - Reza Nejatbakhsh
- Department of Anatomical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
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28
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Zhu T, Lu XT, Liu ZY, Zhu HL. Dietary linoleic acid and the ratio of unsaturated to saturated fatty acids are inversely associated with significant liver fibrosis risk: A nationwide survey. Front Nutr 2022; 9:938645. [PMID: 35958259 PMCID: PMC9360805 DOI: 10.3389/fnut.2022.938645] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 06/20/2022] [Indexed: 11/24/2022] Open
Abstract
Since no pharmaceuticals have been proven to effectively reduce liver fibrosis, dietary fatty acids may be beneficial as one of the non-pharmaceutical interventions due to their important roles in liver metabolism. In this cross-sectional study, we analyzed the data from the 2017–2018 cycle of National Health and Nutrition Examination Survey to examine the associations between the proportion and composition of dietary fatty acid intakes with significant liver fibrosis among US population. The dietary fatty acid consumptions were calculated based on two 24-h dietary recalls. Significant liver fibrosis was diagnosed based on liver stiffness measurement value derived from the vibration controlled transient elastography. Multivariate logistic regression analysis and sensitivity analysis were performed to assess the association between dietary fatty acid consumption and significant liver fibrosis risk. Finally, restricted cubic spline analysis was carried out to explore the dose–response between polyunsaturated fatty acids (PUFA) or linoleic acid intakes and the risk of significant liver fibrosis. The results showed that the multivariate adjusted odds ratios (95% confidence intervals) of significant liver fibrosis were 0.34 (0.14–0.84), 0.68 (0.50–0.91), and 0.64 (0.47–0.87) for the highest level of unsaturated to saturated fatty acid ratio, dietary PUFA, and linoleic acid intakes compared to the lowest reference, respectively. The sensitivity analysis and restricted cubic spline analysis produced similar results, reinforcing the inverse association of unsaturated to saturated fatty acid ratio, PUFA, and linoleic acid consumptions with significant liver fibrosis risk. However, other dietary fatty acids did not show the statistically significant association with significant liver fibrosis. In conclusion, dietary linoleic acid may play a key role in the inverse association between the unsaturated to saturated fatty acid ratio and the risk of significant liver fibrosis. Further studies are needed to confirm these findings.
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Affiliation(s)
- Tingting Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Department of Food Science and Engineering, School of Food Science and Engineering, Hainan Tropical Ocean University, Sanya, China.,Collaborative Innovation Center of Provincial and Ministerial Co-construction for Marine Food Deep Processing, Hainan Tropical Ocean University, Sanya, China
| | - Xiao-Ting Lu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zhao-Yan Liu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Hui-Lian Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
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29
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Zara V, Assalve G, Ferramosca A. Multiple roles played by the mitochondrial citrate carrier in cellular metabolism and physiology. Cell Mol Life Sci 2022; 79:428. [PMID: 35842872 PMCID: PMC9288958 DOI: 10.1007/s00018-022-04466-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 06/17/2022] [Accepted: 07/03/2022] [Indexed: 11/18/2022]
Abstract
The citrate carrier (CIC) is an integral protein of the inner mitochondrial membrane which catalyzes the efflux of mitochondrial citrate (or other tricarboxylates) in exchange with a cytosolic anion represented by a tricarboxylate or a dicarboxylate or phosphoenolpyruvate. In this way, the CIC provides the cytosol with citrate which is involved in many metabolic reactions. Several studies have been carried out over the years on the structure, function and regulation of this metabolite carrier protein both in mammals and in many other organisms. A lot of data on the characteristics of this protein have therefore accumulated over time thereby leading to a complex framework of metabolic and physiological implications connected to the CIC function. In this review, we critically analyze these data starting from the multiple roles played by the mitochondrial CIC in many cellular processes and then examining the regulation of its activity in different nutritional and hormonal states. Finally, the metabolic significance of the citrate flux, mediated by the CIC, across distinct subcellular compartments is also discussed.
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Affiliation(s)
- Vincenzo Zara
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100, Lecce, Italy
| | - Graziana Assalve
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100, Lecce, Italy
| | - Alessandra Ferramosca
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100, Lecce, Italy.
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30
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Martínez-Sanz J, Calvo MV, Serrano-Villar S, Montes ML, Martín-Mateos R, Burgos-Santamaría D, Díaz-Álvarez J, Talavera-Rodríguez A, Rosas M, Moreno S, Fontecha J, Sánchez-Conde M. Effects of HIV Infection in Plasma Free Fatty Acid Profiles among People with Non-Alcoholic Fatty Liver Disease. J Clin Med 2022; 11:jcm11133842. [PMID: 35807127 PMCID: PMC9267237 DOI: 10.3390/jcm11133842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/27/2022] [Accepted: 06/28/2022] [Indexed: 12/10/2022] Open
Abstract
Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.
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Affiliation(s)
- Javier Martínez-Sanz
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (S.S.-V.); (J.D.-Á.); (M.R.); (S.M.)
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (J.M.-S.); (M.S.-C.)
| | - María Visitación Calvo
- Food Lipid Biomarkers and Health Group, Institute of Food Science Research (CIAL, CSIC-UAM), 28049 Madrid, Spain; (M.V.C.); (J.F.)
| | - Sergio Serrano-Villar
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (S.S.-V.); (J.D.-Á.); (M.R.); (S.M.)
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - María Luisa Montes
- HIV Unit—Internal Medicine Service, Hospital Universitario la Paz—IdiPAZ, 28046 Madrid, Spain;
| | - Rosa Martín-Mateos
- Department of Gastroenterology and Hepatology, Metabolic Liver Disease Clinic, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (R.M.-M.); (D.B.-S.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Universidad de Alcalá, 28871 Madrid, Spain
| | - Diego Burgos-Santamaría
- Department of Gastroenterology and Hepatology, Metabolic Liver Disease Clinic, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (R.M.-M.); (D.B.-S.)
| | - Jorge Díaz-Álvarez
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (S.S.-V.); (J.D.-Á.); (M.R.); (S.M.)
| | - Alba Talavera-Rodríguez
- Bioinformatics Unit, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain;
| | - Marta Rosas
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (S.S.-V.); (J.D.-Á.); (M.R.); (S.M.)
| | - Santiago Moreno
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (S.S.-V.); (J.D.-Á.); (M.R.); (S.M.)
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Javier Fontecha
- Food Lipid Biomarkers and Health Group, Institute of Food Science Research (CIAL, CSIC-UAM), 28049 Madrid, Spain; (M.V.C.); (J.F.)
| | - Matilde Sánchez-Conde
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (S.S.-V.); (J.D.-Á.); (M.R.); (S.M.)
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (J.M.-S.); (M.S.-C.)
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31
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Li P, Hu J, Zhao H, Feng J, Chai B. Multi-Omics Reveals Inhibitory Effect of Baicalein on Non-Alcoholic Fatty Liver Disease in Mice. Front Pharmacol 2022; 13:925349. [PMID: 35784718 PMCID: PMC9240231 DOI: 10.3389/fphar.2022.925349] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/06/2022] [Indexed: 12/20/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, whose etiology is poorly understood. Accumulating evidence indicates that gut microbiota plays an important role in the occurrence and progression of various human diseases, including NAFLD. In this study, NAFLD mouse models were established by feeding a high-fat diet (HFD). Baicalein, a natural flavonoid with multiple biological activities, was administered by gavage, and its protective effect on NAFLD was analyzed by histopathological and blood factor analysis. Gut microbiota analysis demonstrated that baicalein could remodel the overall structure of the gut microbiota from NAFLD model mice, especially Anaerotruncus, Lachnoclostridium, and Mucispirillum. Transcriptomic analysis showed baicalein restored the expressions of numerous genes that were upregulated in hepatocytes of NAFLD mice, such as Apoa4, Pla2g12a, Elovl7, Slc27a4, Hilpda, Fabp4, Vldlr, Gpld1, and Apom. Metabolomics analysis proved that baicalein mainly regulated the processes associated with lipid metabolism, such as alpha-Linolenic acid, 2-Oxocarboxylic acid, Pantothenate and CoA biosynthesis, and bile secretion. Multi-omics analysis revealed that numerous genes regulated by baicalein were significantly correlated with pathways related to lipid metabolism and biosynthesis and secrection of bile acid, and baicalein might affect lipid metabolism in liver via regulating the ecological structure of gut microbiota in NAFLD mice. Our results elucidated the correlated network among diet, gut microbiota, metabolomic, and transcriptional profiling in the liver. This knowledge may help explore novel therapeutic approaches against NAFLD.
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Affiliation(s)
- Ping Li
- Institute of Loess Plateau, Shanxi University, Taiyuan, China
- Department of Biological Science and Technology, Jinzhong University, Jinzhong, China
| | - Jianran Hu
- Department of Biological Science and Technology, Jinzhong University, Jinzhong, China
| | - Hongmei Zhao
- Department of Biological Science and Technology, Jinzhong University, Jinzhong, China
| | - Jing Feng
- Department of Gastroenterology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Baofeng Chai
- Institute of Loess Plateau, Shanxi University, Taiyuan, China
- *Correspondence: Baofeng Chai,
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32
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NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules 2022; 12:biom12060824. [PMID: 35740949 PMCID: PMC9221336 DOI: 10.3390/biom12060824] [Citation(s) in RCA: 183] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is one of the most common causes of liver diseases worldwide. NAFLD is growing in parallel with the obesity epidemic. No pharmacological treatment is available to treat NAFLD, specifically. The reason might be that NAFLD is a multi-factorial disease with an incomplete understanding of the mechanisms involved, an absence of accurate and inexpensive imaging tools, and lack of adequate non-invasive biomarkers. NAFLD consists of the accumulation of excess lipids in the liver, causing lipotoxicity that might progress to metabolic-associated steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma. The mechanisms for the pathogenesis of NAFLD, current interventions in the management of the disease, and the role of sirtuins as potential targets for treatment are discussed here. In addition, the current diagnostic tools, and the role of non-coding RNAs as emerging diagnostic biomarkers are summarized. The availability of non-invasive biomarkers, and accurate and inexpensive non-invasive diagnosis tools are crucial in the detection of the early signs in the progression of NAFLD. This will expedite clinical trials and the validation of the emerging therapeutic treatments.
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33
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Tao W, Cao W, Yu B, Chen H, Gong R, Luorong Q, Luo J, Yao L, Zhang D. Hawk tea prevents high-fat diet-induced obesity in mice by activating the AMPK/ACC/SREBP1c signaling pathways and regulating the gut microbiota. Food Funct 2022; 13:6056-6071. [PMID: 35437540 DOI: 10.1039/d1fo04260b] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Scope: Hawk tea, a non-Camellia tea, is an ancient tea drink from southwest China and has been proven to exhibit significant hypoglycaemic and lipid-lowering effects. The aim of this study was to evaluate whether Hawk tea extract (HTE) can improve obesity induced by a high-fat diet (HFD) in a mouse model and to determine whether its anti-obesity effects are related to improvements in lipid metabolism and the gut microbiota. Methods and results: We tested the ability of HTE to prevent obesity and regulate gut microbiota in C57BL/6J mice fed with a HFD. We found that HTE significantly reduced body weight, fat deposition, serum triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, and significantly increased serum levels of high-density lipoprotein cholesterol (HDL-C) induced by HFD. HTE also increased the levels of AMPK and ACC phosphorylation, up-regulated the expression of CPT-1, and downregulated the expression of SREBP1c and FAS. In addition, the administration of HTE significantly altered the composition of the gut microbiota, reduced the ratio of Firmicutes to Bacteroidetes, increased the relative abundance of Akkermansia muciniphila, Bacteroides-vulgatus, and Faecalibaculum_rodentium, and decreased the relative abundance of Desulfovibrionaceae and Lachnospiraceae. Conclusions: Collectively, our data demonstrate that HTE can prevent HFD-induced obesity by regulating the AMPK/ACC/SREBP1c signaling pathways and the gut microbiota.
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Affiliation(s)
- Wei Tao
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Weiguo Cao
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.,The Lab of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
| | - Bao Yu
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Huan Chen
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Ruixue Gong
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Quji Luorong
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Juan Luo
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Ling Yao
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Dan Zhang
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
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34
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Hou Z, Lu X, Tiziani S, Fuiman LA. Nutritional programming by maternal diet alters offspring lipid metabolism in a marine teleost. FISH PHYSIOLOGY AND BIOCHEMISTRY 2022; 48:535-553. [PMID: 35399145 DOI: 10.1007/s10695-022-01069-1] [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: 09/16/2021] [Accepted: 03/25/2022] [Indexed: 06/14/2023]
Abstract
Nutritional programming - the association between the early nutritional environment and long-term consequences for an animal - is an emerging area of research in fish biology. Previous studies reported correlations between maternal provisioning of essential fatty acids to eggs and the whole-body fatty acid composition of larvae reared under uniform conditions for red drum, Sciaenops ocellatus. This study aimed to further investigate the nutritional stimulus and the consequences of nutritional programming by feeding adult red drum several distinct diets and rearing larvae under uniform conditions until 21 days post-hatching when larval lipid and fatty acid compositions were assessed. Different maternal diets produced eggs with distinctive lipid and fatty acid compositions, and despite receiving the same larval diet for almost 3 weeks, larvae showed differences in total fatty acid accumulation and in retention of highly unsaturated fatty acids (HUFA). Specifically, larvae reared from a maternal diet of shrimp generally showed elevated levels of fatty acids in the initial steps of the n-3 and n-6 HUFA biosynthetic pathways and reduced levels of fatty acid products of the same pathways, especially in triglyceride. Furthermore, the variations in larval fatty acid accumulation induced by maternal diet varied among females. Lipid metabolism altered by parental diet may have consequences for larval physiological processes and behavioral performance, which may ultimately influence larval survival.
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Affiliation(s)
- Zhenxin Hou
- The University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX, 78373, USA.
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.
| | - Xiyuan Lu
- Department of Nutritional Sciences and Dell Pediatric Research Institute, The University of Texas at Austin, 1400 Barbara Jordan Blvd., Austin, TX, 78723, USA
| | - Stefano Tiziani
- Department of Nutritional Sciences and Dell Pediatric Research Institute, The University of Texas at Austin, 1400 Barbara Jordan Blvd., Austin, TX, 78723, USA
- Department of Pediatrics and Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Lee A Fuiman
- The University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX, 78373, USA
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35
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Mandala A, Dobrinskikh E, Janssen RC, Fiehn O, D’Alessandro A, Friedman JE, Jonscher KR. Maternal Pyrroloquinoline Quinone Supplementation Improves Offspring Liver Bioactive Lipid Profiles throughout the Lifespan and Protects against the Development of Adult NAFLD. Int J Mol Sci 2022; 23:6043. [PMID: 35682720 PMCID: PMC9181499 DOI: 10.3390/ijms23116043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/18/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric nonalcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal models show that signs of liver injury and perturbed lipid metabolism associated with NAFLD begin in utero; however, safe dietary therapeutics to blunt developmental programming of NAFLD are unavailable. Using a mouse model of maternal Western-style diet (WD), we previously showed that pyrroloquinoline quinone (PQQ), a potent dietary antioxidant, protected offspring of WD-fed dams from development of NAFLD and NASH. Here, we used untargeted mass spectrometry-based lipidomics to delineate lipotoxic effects of WD on offspring liver and identify lipid targets of PQQ. PQQ exposure during pregnancy altered hepatic lipid profiles of WD-exposed offspring, upregulating peroxisome proliferator-activated receptor (PPAR) α signaling and mitochondrial fatty acid oxidation to markedly attenuate triglyceride accumulation beginning in utero. Surprisingly, the abundance of very long-chain ceramides, important in promoting gut barrier and hepatic function, was significantly elevated in PQQ-treated offspring. PQQ exposure reduced the hepatic phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio in WD-fed offspring and improved glucose tolerance. Notably, levels of protective n - 3 polyunsaturated fatty acids (PUFAs) were elevated in offspring exposed to PQQ, beginning in utero, and the increase in n - 3 PUFAs persisted into adulthood. Our findings suggest that PQQ supplementation during gestation and lactation augments pathways involved in the biosynthesis of long-chain fatty acids and plays a unique role in modifying specific bioactive lipid species critical for protection against NAFLD risk in later life.
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Affiliation(s)
- Ashok Mandala
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (J.E.F.)
| | - Evgenia Dobrinskikh
- Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
| | - Rachel C. Janssen
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (J.E.F.)
| | - Oliver Fiehn
- Genome Center-Metabolomics, University of California Davis, Davis, CA 95616, USA;
| | - Angelo D’Alessandro
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
| | - Jacob E. Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (J.E.F.)
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Karen R. Jonscher
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (J.E.F.)
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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36
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Batool M, Ranjha MMAN, Roobab U, Manzoor MF, Farooq U, Nadeem HR, Nadeem M, Kanwal R, AbdElgawad H, Al Jaouni SK, Selim S, Ibrahim SA. Nutritional Value, Phytochemical Potential, and Therapeutic Benefits of Pumpkin ( Cucurbita sp.). PLANTS (BASEL, SWITZERLAND) 2022; 11:1394. [PMID: 35684166 PMCID: PMC9182978 DOI: 10.3390/plants11111394] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/20/2022] [Accepted: 05/21/2022] [Indexed: 05/05/2023]
Abstract
Pumpkin is a well-known multifunctional ingredient in the diet, full of nutrients, and has opened new vistas for scientists during the past years. The fruit of pumpkin including the flesh, seed, and peel are a rich source of primary and secondary metabolites, including proteins, carbohydrates, monounsaturated fatty acids, polyunsaturated fatty acids, carotenoids, tocopherols, tryptophan, delta-7-sterols, and many other phytochemicals. This climber is traditionally used in many countries, such as Austria, Hungary, Mexico, Slovenia, China, Spain, and several Asian and African countries as a functional food and provides health promising properties. Other benefits of pumpkin, such as improving spermatogenesis, wound healing, antimicrobial, anti-inflammatory, antioxidative, anti-ulcerative properties, and treatment of benign prostatic hyperplasia have also been confirmed by researchers. For better drug delivery, nanoemulsions and niosomes made from pumpkin seeds have also been reported as a health promising tool, but further research is still required in this field. This review mainly focuses on compiling and summarizing the most relevant literature to highlight the nutritional value, phytochemical potential, and therapeutic benefits of pumpkin.
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Affiliation(s)
- Maria Batool
- University Institute of Diet and Nutritional Sciences, University of Lahore, Gujrat 50700, Pakistan;
| | | | - Ume Roobab
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China; (U.R.); (R.K.)
| | | | - Umar Farooq
- Department of Food Science and Technology, Muhammad Nawaz Shareef University of Agriculture, Multan 59300, Pakistan;
| | - Hafiz Rehan Nadeem
- Institute of Food Science and Nutrition, Bahauddin Zakariya University, Multan 59300, Pakistan;
| | - Muhammad Nadeem
- Institute of Food Science and Nutrition, University of Sargodha, Sargodha 40100, Pakistan; (M.M.A.N.R.); (M.N.)
| | - Rabia Kanwal
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China; (U.R.); (R.K.)
| | - Hamada AbdElgawad
- Integrated Molecular Plant Physiology Research, Department of Biology, University of Antwerp, 2020 Antwerpen, Belgium;
- Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Soad K. Al Jaouni
- Department of Hematology/Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Samy Selim
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
| | - Salam A. Ibrahim
- Food Microbiology and Biotechnology Laboratory, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA
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37
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Karkucinska-Wieckowska A, Simoes ICM, Kalinowski P, Lebiedzinska-Arciszewska M, Zieniewicz K, Milkiewicz P, Górska-Ponikowska M, Pinton P, Malik AN, Krawczyk M, Oliveira PJ, Wieckowski MR. Mitochondria, oxidative stress and nonalcoholic fatty liver disease: A complex relationship. Eur J Clin Invest 2022; 52:e13622. [PMID: 34050922 DOI: 10.1111/eci.13622] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/19/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023]
Abstract
According to the 'multiple-hit' hypothesis, several factors can act simultaneously in nonalcoholic fatty liver disease (NAFLD) progression. Increased nitro-oxidative (nitroso-oxidative) stress may be considered one of the main contributors involved in the development and risk of NAFLD progression to nonalcoholic steatohepatitis (NASH) characterized by inflammation and fibrosis. Moreover, it has been repeatedly postulated that mitochondrial abnormalities are closely related to the development and progression of liver steatosis and NAFLD pathogenesis. However, it is difficult to determine with certainty whether mitochondrial dysfunction or oxidative stress are primary events or a simple consequence of NAFLD development. On the one hand, increasing lipid accumulation in hepatocytes could cause a wide range of effects from mild to severe mitochondrial damage with a negative impact on cell fate. This can start the cascade of events, including an increase of cellular reactive nitrogen species (RNS) and reactive oxygen species (ROS) production that promotes disease progression from simple steatosis to more severe NAFLD stages. On the other hand, progressing mitochondrial bioenergetic catastrophe and oxidative stress manifestation could be considered accompanying events in the vast spectrum of abnormalities observed during the transition from NAFL to NASH and cirrhosis. This review updates our current understanding of NAFLD pathogenesis and clarifies whether mitochondrial dysfunction and ROS/RNS are culprits or bystanders of NAFLD progression.
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Affiliation(s)
| | - Ines C M Simoes
- Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
| | - Piotr Kalinowski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Lebiedzinska-Arciszewska
- Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland
| | | | - Paolo Pinton
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy
| | - Afshan N Malik
- Department of Diabetes, School of Life Course, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Marcin Krawczyk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.,Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Paulo J Oliveira
- CNC - Center for Neuroscience and Cell Biology, University of Coimbra, CIBB - Centre for Innovative Biomedicine and Biotechnology, Coimbra, Portugal
| | - Mariusz R Wieckowski
- Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
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Maevskaya M, Kotovskaya Y, Ivashkin V, Tkacheva O, Troshina E, Shestakova M, Breder V, Geyvandova N, Doschitsin V, Dudinskaya E, Ershova E, Kodzoeva K, Komshilova K, Korochanskaya N, Mayorov A, Mishina E, Nadinskaya M, Nikitin I, Pogosova N, Tarzimanova A, Shamkhalova M. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. TERAPEVT ARKH 2022; 94:216-253. [PMID: 36286746 DOI: 10.26442/00403660.2022.02.201363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Indexed: 12/15/2022]
Abstract
The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM.
The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described.
The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, etc.), chronic kidney disease (CKD) and the risk of developing hepatocellular cancer (HCC) were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented.
The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid (UDCA) molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered.
The ability of UDCA to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.
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Atefi M, Entezari MH, Vahedi H, Hassanzadeh A. Sesame Oil Ameliorates Alanine Aminotransferase, Aspartate Aminotransferase, and Fatty Liver Grade in Women with Nonalcoholic Fatty Liver Disease Undergoing Low-Calorie Diet: A Randomized Double-Blind Controlled Trial. Int J Clin Pract 2022; 2022:4982080. [PMID: 35685535 PMCID: PMC9159187 DOI: 10.1155/2022/4982080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 11/29/2021] [Indexed: 12/15/2022] Open
Abstract
Background The type and amount of dietary fats play an important role in fat accumulation in the liver. Sesame oil (SO) is a good source of monounsaturated acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Objective This trial aimed at examining the effect of SO consumption on the levels of liver enzymes and the severity of fatty liver in women with nonalcoholic fatty liver disease (NAFLD) undergoing a weight loss diet. Methods This randomized, double-blind, controlled trial was carried out on 60 women with NAFLD. Subjects were randomly assigned to the SO group (n = 30) and sunflower oil (SFO) group (n = 30), each person consuming 30 grams of oil per day for 12 weeks. All the participants received a hypocaloric diet (-500 kcal/day) during the study. Fatty liver grade and liver enzymes were assessed at pre- and postintervention phases. Results 53 patients completed the study. Significant reductions in body weight, body mass index (BMI), waist circumference (WC), and fatty liver grade were observed in both groups (P < 0.05). Following SO, significant decreases in serum aspartate and alanine aminotransferases (AST and ALT) were observed. After adjusting for confounders, ALT, AST, and fatty liver grade of the SO group were significantly reduced compared to the SFO group (P < 0.05). However, the changes in serum alkaline phosphatase (ALP) were not significant (P > 0.05). Conclusions The desired effects of weight loss were reinforced by the consumption of SO through improving fatty liver severity and serum ALT and AST levels in NAFLD patients. Moreover, low-calorie diets may lead to favorable outcomes for NAFLD patients through mitigation of obesity and fatty liver grade.
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Affiliation(s)
- Masoumeh Atefi
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hassan Entezari
- Food Security Research Centre and Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamid Vahedi
- Department of Gastroenterology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Akbar Hassanzadeh
- Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
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Wang Q, Xie T, Zhang T, Deng Y, Zhang Y, Wu Q, Dong M, Luo X. The Role of Changes in Cumulative Lipid Parameter Burden in the Pathogenesis of Type 2 Diabetes Mellitus: A Cohort Study of People Aged 35-65 Years in Rural China. Diabetes Metab Syndr Obes 2022; 15:1831-1843. [PMID: 35733642 PMCID: PMC9208634 DOI: 10.2147/dmso.s363692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/03/2022] [Indexed: 11/23/2022] Open
Abstract
PURPOSE The main purpose of this study was to examine the effect of the cumulative exposure of blood lipid parameters on type 2 diabetes mellitus (T2DM). Another purpose was to explore whether the cumulative burden of blood lipid parameters plays a certain role in the pathogenesis of diet affecting T2DM. PATIENTS AND METHODS A total of 63 cases of diabetes occurred from 2017 to 2020, with an incidence density of 3.71 person-years. The dietary intake of the residents was obtained by using a dietary frequency questionnaire (FFQ). Cumulative lipid parameter burden was calculated according to the number of years (2016-2020) multiplied by total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). A Cox proportional hazard model was used to estimate the effect of cumulative lipid burden on T2DM. A mediating analysis of accelerated failure time (AFT) was used to investigate the mediating effects of certain foods, the cumulative lipid parameter burden and T2DM. RESULTS A higher cumulative TG load corresponded to a higher risk of T2DM onset (Ptrend =0.021). After adjusting for covariates, the highest quartile cumulative TG burden had a 3.462 times higher risk of T2DM than that in the lowest quartile (HR=3.462, 95% CI: 1.297-9.243). Moreover, a higher cumulative HDL load corresponded to a lower risk of T2DM onset (Ptrend =0.006). After adjusting for covariates, the risk of T2DM was 0.314-fold lower in the highest quartile of cumulative HDL burden than that in the lowest quartile (HR=0.314, 95% CI: 0.131-0.753). Cumulative TG burden partially mediated the association between red meat and T2DM. CONCLUSION The increase in cumulative HDL burden and the decrease in cumulative HDL burden are related to the incidence of T2DM. Cumulative TG burden was shown to play a partial mediating role in the pathogenesis of red meat and diabetes.
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Affiliation(s)
- Qi Wang
- Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Tao Xie
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Ting Zhang
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Yuanjia Deng
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Yuying Zhang
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Qingfeng Wu
- Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Minghua Dong
- Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
| | - Xiaoting Luo
- Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China
- School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of China
- Correspondence: Xiaoting Luo, Tel +86 13677975578, Fax +86 0797-8169600, Email
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Marchlewicz E, McCabe C, Djuric Z, Hoenerhoff M, Barks J, Tang L, Song PX, Peterson K, Padmanabhan V, Dolinoy DC. Gestational exposure to high fat diets and bisphenol A alters metabolic outcomes in dams and offspring, but produces hepatic steatosis only in dams. CHEMOSPHERE 2022; 286:131645. [PMID: 34426127 PMCID: PMC8595757 DOI: 10.1016/j.chemosphere.2021.131645] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 06/29/2021] [Accepted: 07/21/2021] [Indexed: 05/07/2023]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Perinatal development is a critical window for altered, lifelong health trajectory, and evidence supports the role of perinatal programming in chronic metabolic diseases. To examine the impact of diet and bisphenol A (BPA) on the developmental trajectory of NAFLD in offspring, we exposed dams from pre-gestation through lactation to a human-relevant dose of oral BPA coupled with intake of high fat Western or Mediterranean-style diets. We assessed hepatic steatosis by quantifying hepatic triglycerides (TGs) and metabolic health by measuring body weight, relative organ weights, and serum hormone levels in dams and offspring at postnatal day 10 (PND10) and 10-months of age. In dams, consumption of the Western or Mediterranean diet increased hepatic TGs 1.7-2.4-fold, independent of BPA intake. Among offspring, both perinatal diet and BPA exposure had a greater impact on metabolic outcomes than on hepatic steatosis. At PND10, serum leptin levels were elevated 2.6-4.8-fold in pups exposed to the Mediterranean diet, with a trend for sex-specific effects on body and organ weights. At 10-months, sex-specific increases in organ weight and hormone levels were observed in mice perinatally exposed to Western + BPA or Mediterranean + BPA. These findings suggest lifestage-specific interaction of perinatal exposures to experimental diets and BPA on offspring metabolic health without effects on NAFLD later in life. Importantly, alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory, emphasizing the need to define dam diet in assessing effects of environmental exposures on offspring health.
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Affiliation(s)
- Elizabeth Marchlewicz
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Carolyn McCabe
- Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Zora Djuric
- Department of Family Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Mark Hoenerhoff
- In Vivo Animal Core, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - John Barks
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Lu Tang
- Department of Biostatistics, University of Pittsburgh, Pittsburg, PA, USA
| | - Peter X Song
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Karen Peterson
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Vasantha Padmanabhan
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Dana C Dolinoy
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
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Craven K, Clement D, Brewster CT, Messenger J, Kolasa KM. Non-Alcoholic Fatty Liver Disease (NAFLD) and Nutrition. NUTRITION TODAY 2021; 56:296-305. [DOI: 10.1097/nt.0000000000000514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Nonalcoholic fatty liver disease is defined as an excess accumulation of fat in the liver in patients with little or no history of alcohol consumption. It is considered difficult to identify and treat in this early, reversible stage and is strongly associated with obesity, insulin resistance (including type 2 diabetes mellitus), metabolic syndrome, and dyslipidemia. The prevalence in both adults and children is increasing. Treatment guidelines from around the world agree that weight loss is the first line of treatment. We discuss diet-related therapies including weight loss and with a special focus on the Mediterranean diet. We present a case from our family medicine practice to demonstrate how evidence-based medical nutrition therapy, along with prescription medication to assist in weight management, can be used to help adult patients with nonalcoholic fatty liver disease. We also comment on recommended treatment for pediatric patients.
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Sotiropoulou M, Katsaros I, Vailas M, Lidoriki I, Papatheodoridis GV, Kostomitsopoulos NG, Valsami G, Tsaroucha A, Schizas D. Nonalcoholic fatty liver disease: The role of quercetin and its therapeutic implications. Saudi J Gastroenterol 2021; 27:319-330. [PMID: 34810376 PMCID: PMC8656328 DOI: 10.4103/sjg.sjg_249_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 08/29/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting almost one-third of the general population and 75% of obese patients with type 2 diabetes. The aim of this article is to review the current evidence concerning the role of quercetin, a natural compound and flavonoid, and its possible therapeutic effects on this modern-day disease. Despite the fact that the exact pathophysiological mechanisms through which quercetin has a hepatoprotective effect on NAFLD are still not fully elucidated, this review clearly demonstrates that this flavonoid has potent antioxidative stress action and inhibitory effects on hepatocyte apoptosis, inflammation, and generation of reactive oxygen species, factors which are linked to the development of the disease. NAFLD is closely associated with increased dietary fat consumption, especially in Western countries. The hepatoprotective effect of quercetin against NAFLD merits serious consideration and further validation by future studies.
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Affiliation(s)
- Maria Sotiropoulou
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Katsaros
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Michail Vailas
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Irene Lidoriki
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Nikolaos G Kostomitsopoulos
- Center of Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Georgia Valsami
- Department of Pharmacy, Laboratory of Biopharmaceutics-Pharmacokinetics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Tsaroucha
- Laboratory of Experimental Surgery, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Guo X, Zheng J, Zhang S, Jiang X, Chen T, Yu J, Wang S, Ma X, Wu C. Advances in Unhealthy Nutrition and Circadian Dysregulation in Pathophysiology of NAFLD. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2021; 2:691828. [PMID: 36994336 PMCID: PMC10012147 DOI: 10.3389/fcdhc.2021.691828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 09/27/2021] [Indexed: 11/13/2022]
Abstract
Unhealthy diets and lifestyle result in various metabolic conditions including metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Much evidence indicates that disruption of circadian rhythms contributes to the development and progression of excessive hepatic fat deposition and inflammation, as well as liver fibrosis, a key characteristic of non-steatohepatitis (NASH) or the advanced form of NAFLD. In this review, we emphasize the importance of nutrition as a critical factor in the regulation of circadian clock in the liver. We also focus on the roles of the rhythms of nutrient intake and the composition of diets in the regulation of circadian clocks in the context of controlling hepatic glucose and fat metabolism. We then summarize the effects of unhealthy nutrition and circadian dysregulation on the development of hepatic steatosis and inflammation. A better understanding of how the interplay among nutrition, circadian rhythms, and dysregulated metabolism result in hepatic steatosis and inflammation can help develop improved preventive and/or therapeutic strategies for managing NAFLD.
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Affiliation(s)
- Xin Guo
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Xin Guo, ; Chaodong Wu,
| | - Juan Zheng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Shixiu Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaofan Jiang
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ting Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Jiayu Yu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Shu'e Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaomin Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chaodong Wu
- Department of Nutrition, Texas A&M University, College Station, TX, United States
- *Correspondence: Xin Guo, ; Chaodong Wu,
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Khandelwal R, Dassanayake AS, Conjeevaram HS, Singh SP. Non-alcoholic fatty liver disease in diabetes: When to refer to the hepatologist? World J Diabetes 2021; 12:1479-1493. [PMID: 34630901 PMCID: PMC8472504 DOI: 10.4239/wjd.v12.i9.1479] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/18/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. A strong relationship exists between NAFLD and diabetes mellitus. There is growing evidence of a mechanistically complex and strong association between the two diseases. Current data also shows that one disease actually leads to worsening of the other and vice versa. Understanding of the various pathophysiological mechanisms involved, natural history and spectrum of these two diseases is essential not only for early diagnosis and management but also for prevention of severe disease forms. Despite the tremendous progress made in recent times in acquiring knowledge about these highly prevalent diseases, the guidelines and recommendations for screening and management of diabetics with NAFLD remain ambiguous. An interdisciplinary approach is required to not only raise awareness of the prevalence of NAFLD in diabetics but also for better patient management. This can help attenuate the development of significant complications, such as cirrhosis, decompensation and hepatocellular carcinoma in these patients, thereby halting NAFLD in its tracks. This review focuses on the pivotal role of primary care physicians and endocrinologists in identification of NAFLD in diabetics in early stages and the role of proactive screening for prompt referral to hepatologist.
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Affiliation(s)
- Reshu Khandelwal
- Department of Gastroenterology, Srirama Chandra Bhanja (SCB) Medical College and Hospital, Cuttack 753007, Odisha, India
| | - Anuradha S Dassanayake
- Department of Medicine, Colombo North Centre for Liver Disease, University of Kelaniya, Kelaniya 11600, Sri Lanka
| | - Hari S Conjeevaram
- Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI 48109, United States
| | - Shivaram P Singh
- Department of Gastroenterology, Srirama Chandra Bhanja (SCB) Medical College and Hospital, Cuttack 753007, Odisha, India
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Li CX, Shen LR. New observations on the effect of camellia oil on fatty liver disease in rats. J Zhejiang Univ Sci B 2021; 21:657-667. [PMID: 32748581 DOI: 10.1631/jzus.b2000101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Camellia oil has become an important plant oil in China in recent years, but its effects on non-alcoholic fatty liver disease (NAFLD) have not been documented. In this study, the effects of camellia oil, soybean oil, and olive oil on NAFLD were evaluated by analyzing the fatty acid profiles of the plant oils, the serum lipids and lipoproteins of rats fed different oils, and by cytological and ultrastructural observation of the rats' hepatocytes. Analysis of fatty acid profiles showed that the polyunsaturated fatty acid (PUFA) n-6/n-3 ratio was 33.33 in camellia oil, 12.50 in olive oil, and 7.69 in soybean oil. Analyses of serum lipids and lipoproteins of rats showed that the levels of total cholesterol and low-density lipoprotein cholesterol in a camellia oil-fed group (COFG) were lower than those in an olive oil-fed group (OOFG) and higher than those in a soybean oil-fed group (SOFG). However, only the difference in total cholesterol between the COFG and SOFG was statistically significant. Cytological observation showed that the degree of lipid droplet (LD) accumulation in the hepatocytes in the COFG was lower than that in the OOFG, but higher than that in the SOFG. Ultrastructural analysis revealed that the size and number of the LDs in the hepatocytes of rats fed each of the three types of oil were related to the degree of damage to organelles, including the positions of nuclei and the integrity of mitochondria and endoplasmic reticulum. The results revealed that the effect of camellia oil on NAFLD in rats was greater than that of soybean oil, but less than that of olive oil. Although the overall trend was that among the three oil diets, those with a lower n-6/n-3 ratio were associated with a lower risk of NAFLD, and the effect of camellia oil on NAFLD was not entirely related to the n-6/n-3 ratio and may have involved other factors. This provides new insights into the effect of oil diets on NAFLD.
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Affiliation(s)
- Chun-Xue Li
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China
| | - Li-Rong Shen
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China
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Harvey DH, Whittaker A, Arnold K, Mills JF, Shchukin DG. Water-in-oil lecithin microcapsule production using an in-line mixer. Colloids Surf A Physicochem Eng Asp 2021. [DOI: 10.1016/j.colsurfa.2021.126510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Cristofano M D, A F, Giacomo M D, C F, F B, D L, Rotondi Aufiero V, F M, E C, G M, V Z, M R, P B. Mechanisms underlying the hormetic effect of conjugated linoleic acid: Focus on Nrf2, mitochondria and NADPH oxidases. Free Radic Biol Med 2021; 167:276-286. [PMID: 33753237 DOI: 10.1016/j.freeradbiomed.2021.03.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/14/2021] [Accepted: 03/15/2021] [Indexed: 12/17/2022]
Abstract
Nuclear factor erythroid 2-related factor2 (Nrf2) is a redox-sensitive transcription factor. Its activation by low dietary intake of ligands leads to antioxidant effects (eustress), while pro-oxidant effects (oxidative distress) may be associated with high doses. NADPH oxidases (NOXs) and the mitochondrial electron transport chain are the main sources of intracellular ROS, but their involvement in the biphasic/hormetic activity elicited by Nrf2 ligands is not fully understood. In this study, we investigated the involvement of NOX expression and mitochondrial function in the hormetic properties of omega-3 typically present in fish oil (FO) and conjugated linoleic acid (CLA) in the mouse liver. Four-week administration of FO, at both low and high doses (L-FO and H-FO) improves Nrf2-activated cyto-protection (by phase 2 enzymes), while a significant increase in respiration efficiency occurs in the liver mitochondria of H-FO BALB/c mice. Eustress conditions elicited by low dose CLA (L-CLA) are associated with increased activity of phase 2 enzymes, and with higher NOX1-2, mitochondrial defences, mitochondrial uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, compared with controls. Steatogenic effects (lipid accumulation and alteration of lipid metabolism) elicited by high CLA (H-CLA) elicited that are associated with oxidative distress, increased mitochondrial complex I/III activity and reduced levels of phase 2 enzymes, in comparison with L-CLA-treated mice. Our results confirm the steatogenic activity of H-CLA and first demonstrate the role of NOX1 and NOX2 in the eustress conditions elicited by L-CLA. Notably, the negative association of the Nrf2/PGC-1α axis with the different CLA doses provides new insight into the mechanisms underlying the hormetic effect triggered by this Nrf2 ligand.
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Affiliation(s)
- Di Cristofano M
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Ferramosca A
- Department of Environmental and Biological Sciences and Technologies, University of Salento, 73100, Lecce, Italy
| | - Di Giacomo M
- Department of Environmental and Biological Sciences and Technologies, University of Salento, 73100, Lecce, Italy
| | - Fusco C
- Institute of Biosciences and Bio-Resources, National Research Council (CNR-IBBR), 80100, Naples, Italy
| | - Boscaino F
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Luongo D
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Vera Rotondi Aufiero
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Maurano F
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Cocca E
- Institute of Biosciences and Bio-Resources, National Research Council (CNR-IBBR), 80100, Naples, Italy
| | - Mazzarella G
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Zara V
- Department of Environmental and Biological Sciences and Technologies, University of Salento, 73100, Lecce, Italy
| | - Rossi M
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy
| | - Bergamo P
- Institute of Food Sciences, National Research Council (CNR-ISA), 83100, Avellino, Italy.
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Su H, Liu D, Shao J, Li Y, Wang X, Gao Q. Aging Liver: Can Exercise be a Better Way to Delay the Process than Nutritional and Pharmacological Intervention? Focus on Lipid Metabolism. Curr Pharm Des 2021; 26:4982-4991. [PMID: 32503400 DOI: 10.2174/1381612826666200605111232] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/18/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Nowadays, the world is facing a common problem that the population aging process is accelerating. How to delay metabolic disorders in middle-aged and elderly people, has become a hot scientific and social issue worthy of attention. The liver plays an important role in lipid metabolism, and abnormal lipid metabolism may lead to liver diseases. Exercise is an easily controlled and implemented intervention, which has attracted extensive attention in improving the health of liver lipid metabolism in the elderly. This article reviewed the body aging process, changes of lipid metabolism in the aging liver, and the mechanism and effects of different interventions on lipid metabolism in the aging liver, especially focusing on exercise intervention. METHODS A literature search was performed using PubMed-NCBI, EBSCO Host and Web of Science, and also a report from WHO. In total, 143 studies were included from 1986 to 15 February 2020. CONCLUSION Nutritional and pharmacological interventions can improve liver disorders, and nutritional interventions are less risky relatively. Exercise intervention can prevent and improve age-related liver disease, especially the best high-intensity interval training intensity and duration is expected to be one of the research directions in the future.
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Affiliation(s)
- Hao Su
- The School of Sport Science, Beijing Sport University, Beijing, China
| | - Dongsen Liu
- The School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Jia Shao
- The Graduate School, Beijing Sport University, Beijing, China
| | - Yinuo Li
- The Graduate School, Beijing Sport University, Beijing, China
| | - Xiaoxia Wang
- The School of Physical Education and Art Education, Beijing Technology and Business University, Beijing, China
| | - Qi Gao
- The School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
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Extra virgin olive oil improved body weight and insulin sensitivity in high fat diet-induced obese LDLr-/-.Leiden mice without attenuation of steatohepatitis. Sci Rep 2021; 11:8250. [PMID: 33859314 PMCID: PMC8050103 DOI: 10.1038/s41598-021-87761-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/30/2021] [Indexed: 02/07/2023] Open
Abstract
Dietary fatty acids play a role in the pathogenesis of obesity-associated non-alcoholic fatty liver disease (NAFLD), which is associated with insulin resistance (IR). Fatty acid composition is critical for IR and subsequent NAFLD development. Extra-virgin olive oil (EVOO) is the main source of monounsaturated fatty acids (MUFA) in Mediterranean diets. This study examined whether EVOO-containing high fat diets may prevent diet-induced NAFLD using Ldlr−/−. Leiden mice. In female Ldlr−/−.Leiden mice, the effects of the following high fat diets (HFDs) were examined: a lard-based HFD (HFD-L); an EVOO-based HFD (HFD-EVOO); a phenolic compounds-rich EVOO HFD (HFD-OL). We studied changes in body weight (BW), lipid profile, transaminases, glucose homeostasis, liver pathology and transcriptome. Both EVOO diets reduced body weight (BW) and improved insulin sensitivity. The EVOOs did not improve transaminase values and increased LDL-cholesterol and liver collagen content. EVOOs and HFD-L groups had comparable liver steatosis. The profibrotic effects were substantiated by an up-regulation of gene transcripts related to glutathione metabolism, chemokine signaling and NF-kappa-B activation and down-regulation of genes relevant for fatty acid metabolism. Collectivelly, EVOO intake improved weight gain and insulin sensitivity but not liver inflammation and fibrosis, which was supported by changes in hepatic genes expression.
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