The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis.
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.
Bost
Frédéric
F
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
Aouadi
Myriam
M
Caron
Leslie
L
Even
Patrick
P
Belmonte
Nathalie
N
Prot
Matthieu
M
Dani
Christian
C
Hofman
Paul
P
Pagès
Gilles
G
Pouysségur
Jacques
J
Le Marchand-Brustel
Yannick
Y
Binétruy
Bernard
B
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
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D007527:Isoenzymes; D048052:Mitogen-Activated Protein Kinase 3