title: ERK1 and ERK2 activation modulates diet-induced obesity in mice.
abstract: Obesity is a worldwide problem, and dietary lipids play an important role in its pathogenesis. Recently, Erk1 knock-out (ERK1-/-) mice have been shown to exhibit low preference for dietary fatty acids. Hence, we maintained Erk1-/-mice on a high-fat diet (HFD) to assess the implication of this mitogen-activated protein (MAP) kinase in obesity. The Erk1-/-mice, fed the HFD, were more obese than wild-type (WT) animals, fed the same diet. Erk1-/-obese mice gained more fat and liver mass than WT obese animals. No difference was observed in daily food and energy intake in HFD-fed both group of animals. However, feed efficiency was higher in Erk1-/-than WT animals. Blood cholesterol, triglyceride and insulin concentrations were higher in Erk1-/-obese mice compared to WT obese animals. Accordingly, homeostatic model assessment of insulin resistance (HOMA-IR) value was higher in Erk1-/-obese mice compared to WT obese animals. Interestingly, only Erk1-/-obese mice, but not WT-obese animals, exhibited high degree of phosphorylation of liver MEK, the upstream regulator of ERK1/2. This phenomenon was associated with high liver ERK2 phosphorylation in Erk1-/-obese mice which also had high liver acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) mRNA expression, suggesting high lipogenesis in these animals. The Erk1-/-obese mice also had low PPAR-α and CPT1β mRNA, indicating low fatty acid oxidation. Our observations suggest that ERK1 and ERK2 might play key roles in the regulation of obesity.
authors.affiliation: Physiologie de la Nutrition & Toxicologie, UMR U1231 INSERM/Université de Bourgogne-Franche Compté (UBFC), Dijon, 21000, France; Département de Biochimie, Biologie Cellulaire et Moléculaire, Université des Frères Mentouri, Constantine, 25000, Algeria.
authors.forename: Amira Sayed
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Physiologie de la Nutrition & Toxicologie, UMR U1231 INSERM/Université de Bourgogne-Franche Compté (UBFC), Dijon, 21000, France; Biochemistry Department, Bharathiar University, Coimbatore, Tamil Nadu, India.
authors.forename: Selvakumar
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Physiologie de la Nutrition & Toxicologie, UMR U1231 INSERM/Université de Bourgogne-Franche Compté (UBFC), Dijon, 21000, France; Département des Sciences de la Vie, Ecole Normale Supérieure de Natitingou, Université de Parakou, 03PB212, Parakou, Benin.
authors.forename: Gado
authors.initials: G
authors.lastname: Dramane
authors.affiliation: Laboratoire de Génétique, Université des Frères Mentouri, Constantine, 25000, Algeria.
authors.forename: Douadi
authors.initials: D
authors.lastname: Khelifi
authors.affiliation: Physiologie de la Nutrition & Toxicologie, UMR U1231 INSERM/Université de Bourgogne-Franche Compté (UBFC), Dijon, 21000, France. Electronic address: Naim.Khan@u-bourgogne.fr.
authors.forename: Naim Akhtar
authors.initials: NA
authors.lastname: Khan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D001835:Body Weight; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Lipids; MAP kinase; Obesity