Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice.

Abstract:

:Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt in adipose tissue. AdipoPten-KO mice also showed marked hyperthermia and increased energy expenditure with induced mitochondriagenesis in adipose tissue, associated with marked reduction of p53, inactivation of Rb, phosphorylation of cyclic AMP response element binding protein (CREB) and increased expression of Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma coactivator 1 alpha. Physiologically, adipose Pten mRNA decreased with exposure to cold and increased with obesity, which were linked to the mRNA alterations of mitochondriagenesis. Our results suggest that altered expression of adipose Pten could regulate insulin sensitivity and energy expenditure. Suppression of adipose Pten may become a beneficial strategy to treat type 2 diabetes and obesity.

journal_name

Nat Med

journal_title

Nature medicine

authors

Komazawa N,Matsuda M,Kondoh G,Mizunoya W,Iwaki M,Takagi T,Sumikawa Y,Inoue K,Suzuki A,Mak TW,Nakano T,Fushiki T,Takeda J,Shimomura I

doi

10.1038/nm1117

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

1208-15

issue

11

eissn

1078-8956

issn

1546-170X

pii

nm1117

journal_volume

10

pub_type

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