Peroxisome proliferator-activated receptor-alpha-null mice have increased white adipose tissue glucose utilization, GLUT4, and fat mass: Role in liver and brain.

Détails

ID Serval
serval:BIB_4BF6D6D4BC30
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Peroxisome proliferator-activated receptor-alpha-null mice have increased white adipose tissue glucose utilization, GLUT4, and fat mass: Role in liver and brain.
Périodique
Endocrinology
Auteur(s)
Knauf C., Rieusset J., Foretz M., Cani P.D., Uldry M., Hosokawa M., Martinez E., Bringart M., Waget A., Kersten S., Desvergne B., Gremlich S., Wahli W., Seydoux J., Delzenne N.M., Thorens B., Burcelin R.
ISSN
0013-7227
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
147
Numéro
9
Pages
4067-4078
Langue
anglais
Résumé
Activation of the peroxisome proliferator-activated receptor (PPAR)-alpha increases lipid catabolism and lowers the concentration of circulating lipid, but its role in the control of glucose metabolism is not as clearly established. Here we compared PPARalpha knockout mice with wild type and confirmed that the former developed hypoglycemia during fasting. This was associated with only a slight increase in insulin sensitivity but a dramatic increase in whole-body and adipose tissue glucose use rates in the fasting state. The white sc and visceral fat depots were larger due to an increase in the size and number of adipocytes, and their level of GLUT4 expression was higher and no longer regulated by the fed-to-fast transition. To evaluate whether these adipocyte deregulations were secondary to the absence of PPARalpha from liver, we reexpresssed this transcription factor in the liver of knockout mice using recombinant adenoviruses. Whereas more than 90% of the hepatocytes were infected and PPARalpha expression was restored to normal levels, the whole-body glucose use rate remained elevated. Next, to evaluate whether brain PPARalpha could affect glucose homeostasis, we activated brain PPARalpha in wild-type mice by infusing WY14643 into the lateral ventricle and showed that whole-body glucose use was reduced. Hence, our data show that PPARalpha is involved in the regulation of glucose homeostasis, insulin sensitivity, fat accumulation, and adipose tissue glucose use by a mechanism that does not require PPARalpha expression in the liver. By contrast, activation of PPARalpha in the brain stimulates peripheral glucose use. This suggests that the alteration in adipocyte glucose metabolism in the knockout mice may result from the absence of PPARalpha in the brain.
Mots-clé
Adipocytes, Adipose Tissue, Animals, Blood Glucose, Body Composition, Brain, Cell Size, Fasting, Female, Glucose, Glucose Transporter Type 4, Hepatocytes, Hypothalamus, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuropeptides, PPAR alpha, Peroxisome Proliferators, Pyrimidines, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:41
Dernière modification de la notice
20/08/2019 14:00
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