Essential fatty acids deficiency promotes lipogenic gene expression and hepatic steatosis through the liver X receptor

• Published in: Journal of hepatology Vol. 58; no. 5; pp. 984 - 992
• Main Authors: Ducheix, Simon, Montagner, Alexandra, Polizzi, Arnaud, Lasserre, Frédéric, Marmugi, Alice, Bertrand-Michel, Justine, Podechard, Normand, Al Saati, Talal, Chétiveaux, Maud, Baron, Silvère, Boué, Jérôme, Dietrich, Gilles, Mselli-Lakhal, Laila, Costet, Philippe, Lobaccaro, Jean-Marc A., Pineau, Thierry, Theodorou, Vassilia, Postic, Catherine, Martin, Pascal G.P., Guillou, Hervé
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2013; Elsevier
• Subjects: Animals; Cholesterol; Cholesterol - metabolism; Deficiency Diseases - physiopathology; Dietary Fats - pharmacology; Disease Models, Animal; Fatty Acids, Essential - deficiency; Fatty Liver - physiopathology; Female; Gastroenterology and Hepatology; Gene Expression - drug effects; Gene Expression - physiology; Human health and pathology; Hépatology and Gastroenterology; Life Sciences; Lipogenesis; Lipogenesis - drug effects; Lipogenesis - genetics; Lipogenesis - physiology; Liver - metabolism; Liver X Receptors; LXR; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Orphan Nuclear Receptors - deficiency; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - physiology; Polyunsaturated fatty acids; Steatosis; Transcription Factors - physiology; Triglycerides - metabolism; Up-Regulation - physiology; NAFLD; EFAD; PUFA; Polyunsaturated fatty acids; HNF4α; LXR; WAT; SREBP-1c; Cholesterol; Steatosis; ChREBP; TG; PPAR; EPA; FA; DHA; Lipogenesis; TR; triglyceride; essential fatty acids deficiency; non-alcoholic fatty liver disease; white adipose tissue; polyunsaturated fatty acids; fatty acid; hepatic nuclear factor 4α; sterol responsive element binding protein 1c; thyroid receptor; docosahexaenoic acid; peroxisome proliferator-activated receptor; liver X receptor; carbohydrate response element binding protein; eicosapentaenoic acid
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2013.01.006

Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.