title: The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis.
abstract: Hyperplasia of adipose tissue is critical for the development of obesity, but molecular mechanisms governing normal or pathological recruitment of new adipocytes remain unclear. The extracellular signal-regulated kinase (ERK) pathway plays a pivotal role in many essential cellular functions, such as proliferation and differentiation. Using ERK1(-/-) mice, we investigated the role of this isoform in adipose tissue development. Mice lacking ERK1 have decreased adiposity and fewer adipocytes than wild-type animals. Furthermore, ERK1(-/-) mice challenged with high-fat diet are resistant to obesity, are protected from insulin resistance, and have a higher postprandial metabolic rate. To get insights into cellular mechanisms implicated in reduced adiposity in ERK1(-/-) animals, we analyzed adipocyte differentiation in ERK1(-/-) cells. Compared with wild-type control cells, mouse embryo fibroblasts and cultures of adult preadipocytes isolated from ERK1(-/-) adult animals exhibit impaired adipogenesis. An inhibitor of the ERK pathway does not affect the residual adipogenesis of the ERK1(-/-) cells, suggesting that ERK2 is not implicated in adipocyte differentiation. Our results clearly link ERK1 to the regulation of adipocyte differentiation, adiposity, and high-fat diet-induced obesity. This suggests that a therapeutic approach of obesity targeting specifically the ERK1 isoform and not ERK2 would be of particular interest.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 568, IFR 50, Faculté de Médecine, Université de Nice- Sophia Antipolis, Avenue de Valombrose, Nice, France. bost@unice.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bost
authors.forename: Myriam
authors.initials: M
authors.lastname: Aouadi
authors.forename: Leslie
authors.initials: L
authors.lastname: Caron
authors.forename: Patrick
authors.initials: P
authors.lastname: Even
authors.forename: Nathalie
authors.initials: N
authors.lastname: Belmonte
authors.forename: Matthieu
authors.initials: M
authors.lastname: Prot
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Gilles
authors.initials: G
authors.lastname: Pagès
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Marchand-Brustel
authors.forename: Bernard
authors.initials: B
authors.lastname: Binétruy
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000273:Adipose Tissue / Q000196:embryology / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000494:pharmacology*; D004622:Embryo, Mammalian; D004734:Energy Metabolism / Q000502:physiology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D007527:Isoenzymes; D048052:Mitogen-Activated Protein Kinase 3