Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition

Bd Pachikian,Ya Carpentier,Lb Bindels,L Deldicque,Pd Cani,L Portois,Fc De Backer,Wj Malaisse,M Francaux,Fm Sohet,Am Neyrinck,Nm Delzenne

doi:10.1186/1472-6793-8-21

Abstract

BackgroundThere are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic metabolism.Resultsn-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol) as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPARγ), and an increased β-oxidation (CPT1, PPARα and PGC1α) without modification of fatty acid esterification (DGAT2, GPAT1), secretion (MTTP) or intracellular transport (L-FABP). Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice.Conclusionn-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between β-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency.

Highlights

There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids
Dietary n-3 polyunsaturated fatty acids (PUFA) have important metabolic effects namely through their involvement in eicosanoid biosynthesis and their ability to modulate the transcription of regulatory genes [1,2,3,4]. n3 PUFA are able to coordinate an upregulation of lipid oxidation and a downregulation of lipid synthesis [5,6,7]
Parameters related to glucose metabolism (Table 3) Low n-3 mice exhibited a higher fasting glycaemia compared to CT mice with no effect on fasting insulinemia

Summary

Introduction

There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. Dietary n-3 polyunsaturated fatty acids (PUFA) have important metabolic effects namely through their involvement in eicosanoid biosynthesis and their ability to modulate the transcription of regulatory genes [1,2,3,4]. Several studies have reported the influence of n-3 PUFA supplementation on inflammation and lipid and glucose metabolism [14] Their results give evidence of the beneficial effects of these fatty acids on triglyceridemia [7], blood pressure [15], inflammation [16,17] and insulin sensitivity [18,19]. The rationale to propose dietary supplementation with n-3 PUFA is based on the fact that obese people have a lower level of n-3 PUFA in plasma [20,21], liver and erythrocyte phospholipids (PL) [22]

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