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Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):69-78. doi: 10.1016/j.bbadis.2017.10.002. Epub 2017 Oct 3.

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

Author information

1
Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK. Electronic address: D.Vauzour@uea.ac.uk.
2
Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK.
3
Gastroenterology, Norfolk and Norwich University Hospital, Norwich, UK.
4
Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
5
Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia (UEA), Norwich, UK; Biological Sciences, UEA, UK.
6
Pancreatic Cancer Centre, Cambridge University, Cambridge, UK.
7
The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.
8
Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Madrid, Spain.
9
Biological Sciences, UEA, UK.

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.

KEYWORDS:

Bile acids; Fish oil; Flavonoids; NASH; Srebp-1c

PMID:
28986308
DOI:
10.1016/j.bbadis.2017.10.002
[Indexed for MEDLINE]
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