Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets.
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...
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2011
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oai:doaj.org-article:75626a5b5bac47a482041ccc4a1738232021-11-18T06:48:17ZHepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets.1932-620310.1371/journal.pone.0023365https://doaj.org/article/75626a5b5bac47a482041ccc4a1738232011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21853118/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Patients 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.Barbara D PachikianAhmed EssaghirJean-Baptiste DemoulinAudrey M NeyrinckEmilie CatryFabienne C De BackerNicolas DejeansEvelyne M DewulfFlorence M SohetLaurence PortoisLouise DeldicqueOlivier Molendi-CosteIsabelle A LeclercqMarc FrancauxYvon A CarpentierFabienne FoufelleGiulio G MuccioliPatrice D CaniNathalie M DelzennePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23365 (2011) |
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Medicine R Science Q Barbara D Pachikian Ahmed Essaghir Jean-Baptiste Demoulin Audrey M Neyrinck Emilie Catry Fabienne C De Backer Nicolas Dejeans Evelyne M Dewulf Florence M Sohet Laurence Portois Louise Deldicque Olivier Molendi-Coste Isabelle A Leclercq Marc Francaux Yvon A Carpentier Fabienne Foufelle Giulio G Muccioli Patrice D Cani Nathalie M Delzenne Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| description |
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. |
| format |
article |
| author |
Barbara D Pachikian Ahmed Essaghir Jean-Baptiste Demoulin Audrey M Neyrinck Emilie Catry Fabienne C De Backer Nicolas Dejeans Evelyne M Dewulf Florence M Sohet Laurence Portois Louise Deldicque Olivier Molendi-Coste Isabelle A Leclercq Marc Francaux Yvon A Carpentier Fabienne Foufelle Giulio G Muccioli Patrice D Cani Nathalie M Delzenne |
| author_facet |
Barbara D Pachikian Ahmed Essaghir Jean-Baptiste Demoulin Audrey M Neyrinck Emilie Catry Fabienne C De Backer Nicolas Dejeans Evelyne M Dewulf Florence M Sohet Laurence Portois Louise Deldicque Olivier Molendi-Coste Isabelle A Leclercq Marc Francaux Yvon A Carpentier Fabienne Foufelle Giulio G Muccioli Patrice D Cani Nathalie M Delzenne |
| author_sort |
Barbara D Pachikian |
| title |
Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| title_short |
Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| title_full |
Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| title_fullStr |
Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| title_full_unstemmed |
Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| title_sort |
hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/75626a5b5bac47a482041ccc4a173823 |
| work_keys_str_mv |
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| _version_ |
1718424358530056192 |