The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes.
Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.
Wang
Li
L
Department of Medicine, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Liu
Jun
J
Saha
Pradip
P
Huang
Jiansheng
J
Chan
Lawrence
L
Spiegelman
Bruce
B
Moore
David D
DD
D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000648:ultrastructure; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000166:cytology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009765:Obesity / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation
D008055:Lipids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; C099713:nuclear receptor subfamily 0, group B, member 2