1: BMC Physiol. 2008 Dec 1;8:21.

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

Pachikian BD, Neyrinck AM, Cani PD, Portois L, Deldicque L, De Backer FC, Bindels
LB, Sohet FM, Malaisse WJ, Francaux M, Carpentier YA, Delzenne NM.

Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université
catholique de Louvain, Brussels, Belgium. barbara.pachikian@uclouvain.be

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, PPAR gamma), and an
increased beta-oxidation (CPT1, PPAR alpha and PGC1 alpha) 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 beta-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.

PMCID: PMC2612019
PMID: 19046413 [PubMed - in process]

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