Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle.

Détails

ID Serval
serval:BIB_2464A90C3861
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle.
Périodique
Journal of Biological Chemistry
Auteur(s)
Martin T.L., Alquier T., Asakura K., Furukawa N., Preitner F., Kahn B.B.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2006
Volume
281
Numéro
28
Pages
18933-18941
Langue
anglais
Résumé
AMP-activated protein kinase (AMPK) is a key regulator of cellular energy balance and of the effects of leptin on food intake and fatty acid oxidation. Obesity is usually associated with resistance to the effects of leptin on food intake and body weight. To determine whether diet-induced obesity (DIO) impairs the AMPK response to leptin in muscle and/or hypothalamus, we fed FVB mice a high fat (55%) diet for 10-12 weeks. Leptin acutely decreased food intake by approximately 30% in chow-fed mice. DIO mice tended to eat less, and leptin had no effect on food intake. Leptin decreased respiratory exchange ratio in chow-fed mice indicating increased fatty acid oxidation. Respiratory exchange ratio was low basally in high fat-fed mice, and leptin had no further effect. Leptin (3 mg/kg intraperitoneally) increased alpha2-AMPK activity 2-fold in muscle in chow-fed mice but not in DIO mice. Leptin decreased acetyl-CoA carboxylase activity 40% in muscle from chow-fed mice. In muscle from DIO mice, acetyl-CoA carboxylase activity was basally low, and leptin had no further effect. In paraventricular, arcuate, and medial hypothalamus of chow-fed mice, leptin inhibited alpha2-AMPK activity but not in DIO mice. In addition, leptin increased STAT3 phosphorylation 2-fold in arcuate of chow-fed mice, but this effect was attenuated because of elevated basal STAT3 phosphorylation in DIO mice. Thus, DIO in FVB mice alters alpha2-AMPK in muscle and hypothalamus and STAT3 in hypothalamus and impairs further effects of leptin on these signaling pathways. Defective responses of AMPK to leptin may contribute to resistance to leptin action on food intake and energy expenditure in obese states.
Mots-clé
AMP-Activated Protein Kinases, Acetyl-CoA Carboxylase/metabolism, Animal Feed, Animals, Body Weight, Energy Metabolism, Fatty Acids/metabolism, Hypothalamus/enzymology, Hypothalamus/pathology, Leptin/metabolism, Male, Mice, Multienzyme Complexes/physiology, Muscle, Skeletal/enzymology, Obesity, Oxygen/metabolism, Protein-Serine-Threonine Kinases/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/12/2012 15:56
Dernière modification de la notice
20/08/2019 13:02
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