title: 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.
authors.affiliation: Department of Anatomy and Physiology, School of Medicine, Laval University, Québec, Canada G1K 7P4.
authors.forename: Henrike
authors.initials: H
authors.lastname: Sell
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Pierre
authors.initials: P
authors.lastname: Samson
authors.forename: Gino
authors.initials: G
authors.lastname: Castriota
authors.forename: Josée
authors.initials: J
authors.lastname: Lalonde
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001823:Body Composition; D004734:Energy Metabolism; D005260:Female; D007473:Ion Channels; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism*; D010940:Plant Proteins; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000502:physiology*; D014157:Transcription Factors / Q000819:agonists / Q000502:physiology*; D014280:Triglycerides / Q000097:blood; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010940:Plant Proteins; D022702:Receptors, Adrenergic, beta-3; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1