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© 2011 Pachikian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Patients with non-alcoholic fatty liver disease are characterised by a decreased n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The metabolic consequences of n-3 PUFA depletion in the liver are poorly understood. We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by feeding C57Bl/6J mice for 3 months with an n-3 PUFA depleted diet (DEF) versus a control diet (CT), which only differed in the PUFA content. DEF mice exhibited hepatic insulin resistance (assessed by euglycemic-hyperinsulinemic clamp) and steatosis that was associated with a decrease in fatty acid oxidation and occurred despite a higher capacity for triglyceride secretion. Microarray and qPCR analysis of the liver tissue revealed higher expression of all the enzymes involved in lipogenesis in DEF mice compared to CT mice, as well as increased expression and activation of sterol regulatory element binding protein-1c (SREBP-1c). Our data suggest that the activation of the liver X receptor pathway is involved in the overexpression of SREBP-1c, and this phenomenon cannot be attributed to insulin or to endoplasmic reticulum stress responses. In conclusion, n-3 PUFA depletion in liver phospholipids leads to activation of SREBP-1c and lipogenesis, which contributes to hepatic steatosis.

Details

Title
Hepatic n-3 Polyunsaturated Fatty Acid Depletion Promotes Steatosis and Insulin Resistance in Mice: Genomic Analysis of Cellular Targets
Author
Pachikian, Barbara D; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Neyrinck, Audrey M; Catry, Emilie; De Backer, Fabienne C; Dejeans, Nicolas; Dewulf, Evelyne M; Sohet, Florence M; Portois, Laurence; Deldicque, Louise; Molendi-Coste, Olivier; Leclercq, Isabelle A; Francaux, Marc; Carpentier, Yvon A; Foufelle, Fabienne; Muccioli, Giulio G; Cani, Patrice D; Delzenne, Nathalie M
First page
e23365
Section
Research Article
Publication year
2011
Publication date
Aug 2011
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1307377498
Copyright
© 2011 Pachikian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.