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Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice : genomic analysis of cellular targets.

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Pachikian, Barbara D. [UCL] Essaghir, Ahmed [UCL] Demoulin, Jean-Baptiste [UCL] Neyrinck, Audrey M. [UCL] Catry, Emilie [UCL] De Backer, Fabienne [UCL] Dejeans, Nicolas [UCL] Dewulf, Evelyne [UCL] Sohet, Florence [UCL] Molendi-Coste, Olivier [UCL] Leclercq, Isabelle [UCL] Francaux, Marc [UCL] Muccioli, Giulio [UCL] Cani, Patrice D. [UCL] Delzenne, Nathalie M. [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès libre
Publication date 2011
Language Anglais
Journal information "PLoS One" - Vol. 6, no. 8, p. e23365 (2011)
Peer reviewed yes
Publisher Public Library of Science ((United States) San Francisco, CA)
e-issn 1932-6203
Publication status Publié
Affiliations UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie
UCL - SSS/LDRI - Louvain Drug Research Institute
UCL - SSS/IONS - Institute of NeuroScience
UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
UCL - (SLuc) Service d'hépato-gastro-entérologie
UCL - SSS/DDUV/MEXP - Médecine expérimentale
MESH Subject Triglycerides - metabolism ; Sterol Regulatory Element Binding Protein 1 - metabolism ; Reproducibility of Results ; RNA, Messenger - genetics - metabolism ; Phospholipids - metabolism ; Oxidation-Reduction ; Orphan Nuclear Receptors - metabolism ; Oligonucleotide Array Sequence Analysis ; Mice ; Liver - metabolism - pathology ; Lipid Metabolism - genetics ; Insulin Resistance - genetics ; Genome - genetics ; Gene Expression Regulation ; Feeding Behavior ; Fatty Liver - genetics - pathology ; Fatty Acids, Omega-3 - metabolism ; Endoplasmic Reticulum Stress - genetics ; Endocannabinoids - metabolism ; Diet ; Cholesterol - biosynthesis ; Animals
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Bibliographic reference Pachikian, Barbara D. ; Essaghir, Ahmed ; Demoulin, Jean-Baptiste ; Neyrinck, Audrey M. ; Catry, Emilie ; et. al. Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice : genomic analysis of cellular targets.. In: PLoS One, Vol. 6, no. 8, p. e23365 (2011)
Permanent URL http://hdl.handle.net/2078.1/95891