PPARgamma in the control of brown adipocyte differentiation.
The effects of fatty acids and retinoic acid (carotene) on brown adipose tissue differentiation are mediated by activation of the transcription factors PPARgamma and PPARalpha in combination with RXR. There is good support for the idea that activated PPARgamma promotes adipogenesis also in brown adipose tissue. However, the issue is more complex concerning the full differentiation to the brown adipocyte phenotype, particularly the expression of the brown-fat-specific marker UCP1. The effect of norepinephrine on PPARgamma gene expression, at least in-vitro, is negative, PPARgamma-ablated brown adipose tissue can express UCP1, and PGC-1alpha coactivates other transcription factors (including PPARalpha); thus, the significance of PPARgamma for the physiological control of UCP1 gene expression is not settled. However, importantly, the effects of PPAR agonists demonstrate the existence of a pathway for brown adipose tissue recruitment that is not dependent on chronic adrenergic stimulation and may be active in recruitment conditions such as prenatal and prehibernation recruitment. The ability of chronic PPARgamma agonist treatment to promote the occurrence of brown-fat features in white adipose tissue-like depots implies a role in anti-obesity treatment, but this will only be effective if the extra thermogenic capacity is activated by adrenergic stimulation.
Nedergaard
Jan
J
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden. jan@metabol.su.se
Petrovic
Natasa
N
Lindgren
Eva M
EM
Jacobsson
Anders
A
Cannon
Barbara
B
D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000196:embryology; D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D024101:Mitochondrial Proteins; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology*; D022722:Thermogenesis; D045162:Thiazolidinediones; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D009638:Norepinephrine