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n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD.

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD.

Authors+Show Affiliations

Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK. Electronic address: D.Vauzour@uea.ac.uk.Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK.Gastroenterology, Norfolk and Norwich University Hospital, Norwich, UK.Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK; Biological Sciences, UEA, UK.Pancreatic Cancer Centre, Cambridge University, Cambridge, UK.Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK.The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Madrid, Spain.The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.Biological Sciences, UEA, UK.Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28986308

Citation

Vauzour, David, et al. "N-3 Fatty Acids Combined With Flavan-3-ols Prevent Steatosis and Liver Injury in a Murine Model of NAFLD." Biochimica Et Biophysica Acta. Molecular Basis of Disease, vol. 1864, no. 1, 2018, pp. 69-78.
Vauzour D, Rodriguez-Ramiro I, Rushbrook S, et al. N-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD. Biochim Biophys Acta Mol Basis Dis. 2018;1864(1):69-78.
Vauzour, D., Rodriguez-Ramiro, I., Rushbrook, S., Ipharraguerre, I. R., Bevan, D., Davies, S., ... Minihane, A. M. (2018). N-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD. Biochimica Et Biophysica Acta. Molecular Basis of Disease, 1864(1), pp. 69-78. doi:10.1016/j.bbadis.2017.10.002.
Vauzour D, et al. N-3 Fatty Acids Combined With Flavan-3-ols Prevent Steatosis and Liver Injury in a Murine Model of NAFLD. Biochim Biophys Acta Mol Basis Dis. 2018;1864(1):69-78. PubMed PMID: 28986308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD. AU - Vauzour,David, AU - Rodriguez-Ramiro,Ildefonso, AU - Rushbrook,Simon, AU - Ipharraguerre,Ignacio R, AU - Bevan,Damon, AU - Davies,Susan, AU - Tejera,Noemi, AU - Mena,Pedro, AU - de Pascual-Teresa,Sonia, AU - Del Rio,Daniele, AU - Gavrilovic,Jelena, AU - Minihane,Anne Marie, Y1 - 2017/10/03/ PY - 2017/06/22/received PY - 2017/09/18/revised PY - 2017/10/02/accepted PY - 2017/10/8/pubmed PY - 2018/3/27/medline PY - 2017/10/8/entrez KW - Bile acids KW - Fish oil KW - Flavonoids KW - NASH KW - Srebp-1c SP - 69 EP - 78 JF - Biochimica et biophysica acta. Molecular basis of disease JO - Biochim Biophys Acta Mol Basis Dis VL - 1864 IS - 1 N2 - Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD. SN - 0925-4439 UR - https://www.unboundmedicine.com/medline/citation/28986308/n_3_Fatty_acids_combined_with_flavan_3_ols_prevent_steatosis_and_liver_injury_in_a_murine_model_of_NAFLD_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(17)30357-5 DB - PRIME DP - Unbound Medicine ER -