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Peroxisome proliferator-activated receptor gamma agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice.

Abstract：

:The nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma modulates the expression of numerous genes involved in glucose and lipid homeostasis and plays a critical role in adipocyte differentiation. Expression of uncoupling protein (UCP)1, which is necessary for thermogenesis, is strongly stimulated by PPARgamma agonists but without an increase in energy expenditure. This study was designed to assess whether PPARgamma-induced UCP1 has any functional impact and, if so, whether it involves sympathetic activity. In a first phase, obese ob/ob C57BL/6J mice and lean controls were treated for 2 wk with the PPARgamma agonist [2-(2-[4-phenoxy-2-propylphenoxy]ethyl)indole-5-acetic acid] (COOH). COOH induced UCP1 expression in brown and white adipose tissues as well as that of other genes associated with substrate oxidation and thermogenesis. However, UCP1 induction did not increase energy expenditure, as assessed by indirect calorimetry and other energy balance measurements. In a second phase, mice received for an additional 2 wk a combination of COOH and the beta(3)-adrenergic receptor (beta(3)-AR) agonist CL-316243 to stimulate the adrenergic signaling pathway and assess whether COOH-induced UCP1 was physiologically functional. The beta(3)-AR agonist stimulated thermogenesis in lean and ob/ob mice, an effect that was much stronger in COOH-pretreated mice, which exhibited lower respiratory quotient, higher oxygen consumption, and marked weight and fat mass loss, compared with mice not pretreated with COOH. These results demonstrate that PPARgamma agonism increases the thermogenic potential of white and brown adipose depots in lean and obese mice. This enhanced capacity leads to increased thermogenesis under beta-adrenergic stimulation, suggesting that the sympathetic drive is blunted by PPARgamma agonism.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Sell H,Berger JP,Samson P,Castriota G,Lalonde J,Deshaies Y,Richard D

doi

10.1210/en.2004-0321

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

3925-34

issue

eissn

0013-7227

issn

1945-7170

pii

en.2004-0321

journal_volume

145

pub_type

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Peroxisome proliferator-activated receptor gamma agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice.