Substitution of linoleic acid with \u03b1-linolenic acid or long chain n-3 polyunsaturated fatty acid prevents Western diet induced nonalcoholic steatohepatitis

Sugeedha Jeyapal,Surekha Venkata Mullapudi,Ahamed Ibrahim,Puvaneswari Gurumurthy,Suryam Reddy Kona,Uday Kumar Putcha

doi:10.1038/s41598-018-29222-y

Sugeedha Jeyapal, Surekha Venkata Mullapudi + Show 4 more

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https://doi.org/10.1038/s41598-018-29222-y

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Journal: Scientific Reports	Publication Date: Jul 19, 2018
Citations: 47	License type: open-access

Affiliation: National Institute of Nutrition

Abstract

Imbalance in the n-6 polyunsaturated fatty acids (PUFA) and n-3 PUFA in the Western diet may increase the risk of nonalcoholic fatty liver disease (NAFLD). This study investigates the impact of substitution of linoleic acid with α-linolenic acid (ALA) or long chain (LC) n-3 PUFA and hence decreasing n-6:n-3 fatty acid ratio on high fat, high fructose (HFHF) diet induced nonalcoholic steatohepatitis (NASH). Male Sprague-Dawley rats were divided into four groups and fed control diet, HFHF diet (n-6:n-3 ratio of 200), HFHF diet with ALA (n-6:n-3 ratio of 2) or HFHF diet with LC n-3 PUFA (n-6:n-3 ratio of 5) for 24 weeks. Rats fed HFHF diet with n-6:n-3 ratio of 200 resulted in hepatic steatosis, induced glucose intolerance, insulin resistance and oxidative stress accompanied by increase in markers of inflammation, plasma lipids and aminotransferase levels. Histopathological examination of liver further confirmed the establishment of NASH. ALA and LC n-3 PUFA supplementation prevented hepatic steatosis and dyslipidemia by inhibiting lipogenesis and increasing insulin sensitivity. Furthermore, n-3 PUFA supplementation attenuated hepatic oxidative stress by restoring antioxidant status, decreased inflammation and preserved hepatic architecture. These finding suggest that decreasing n-6:n-3 ratio prevented HFHF induced NASH by attenuating oxidative stress and inflammation.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the chronic liver disease of unknown etiology and is more common in affluent countries, affecting both adults and children
The weights of retroperitoneal and mesenteric fat pads were increased by 70% (P < 0.001) and 30% (P = 0.045) respectively in rats fed diet with HFHF compared to control diet fed rats
In the present study by mimicking typical Western diet, we investigated the impact of substitution of n-6 polyunsaturated fatty acids (PUFA) with n-3 PUFA on the development of nonalcoholic steatohepatitis (NASH)

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the chronic liver disease of unknown etiology and is more common in affluent countries, affecting both adults and children. Western diets are known to induce NAFLD, it is not clear how the individual components of the Western diet influence the development/progression of NAFLD In this context, our recent study demonstrated that in a series of high energy diets mimicking Western diet, the type of dietary fat determines the development of advanced form of NAFLD15. High intake of n-6 PUFA create proinflammatory milieu, which in turn, may affect the development or progression of several diet related chronic diseases including NAFLD17. Transgenic mice engineered to express FAT-1 gene encoding n-3 fatty acid desaturase, which is capable of converting n-6 PUFA to LC n-3 PUFA prevents high fat[26] and Western diet[27] induced NAFLD by restoring LC n-3 PUFA. The impact of n-3 PUFA supplementation on hepatic oxidative stress and expression of genes related to lipid metabolism and inflammation were studied to understand the possible molecular mechanism by which n-3 PUFA supplementation prevents NASH

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