Research article

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

BD Pachikian¹ , AM Neyrinck¹ , PD Cani¹ , L Portois² , L Deldicque³ , FC De Backer¹ , LB Bindels¹ , FM Sohet¹ , WJ Malaisse² , M Francaux³ , YA Carpentier² and NM Delzenne¹

¹  Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium

²  Laboratory of Experimental Surgery, Université Libre de Bruxelles, Brussels, Belgium

³  Department of Physical Education and Rehabilitation, Université catholique de Louvain, Louvain-la-Neuve, Belgium

author email corresponding author email

BMC Physiology 2008, 8:21doi:10.1186/1472-6793-8-21

Published:	1 December 2008

Abstract

Background

There 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.

Results

n-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.

Conclusion

n-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.