Nuclear receptor coactivator PNRC2 regulates energy expenditure and adiposity.
PNRC2 was identified in our laboratory as a general cofactor for nuclear receptors. To better characterize the physiological function of PNRC2, we used gene-targeting technology to generate PNRC2-null mice (PNRC2(-/-) mice). These PNRC2(-/-) mice are viable and fertile. PNRC2-null mice, especially male mice, are lean and are resistant to high fat diet-induced obesity but without the induction of insulin resistance. Male mice devoid of PNRC2 protein have a higher metabolic rate than wild-type mice. They consume more oxygen and produce more heat. Consistent with reduced adipose mass, the levels of leptin are lower in PNRC2(-/-) mice. This study provides evidence that PNRC2 plays one or more important roles in controlling the energy balance between energy storage and energy expenditure. PNRC2 may be a new target in the treatment of obesity and related metabolic diseases.
Zhou
Dujin
D
Department of Surgical Research, Duarte, California 91010.
Shen
Ruoqing
R
Department of Surgical Research, Duarte, California 91010.
Ye
Jing Jing
JJ
Department of Surgical Research, Duarte, California 91010.
Li
Yuping
Y
Department of Surgical Research, Duarte, California 91010.
Tsark
Walter
W
Transgenic Mouse Facility, Duarte, California 91010.
Isbell
Donna
D
Animal Resources Center, Beckman Research Institute of City of Hope, Duarte, California 91010.
Tso
Patrick
P
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529.
Chen
Shiuan
S
Department of Surgical Research, Duarte, California 91010. Electronic address: schen@coh.org.
D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015992:Body Mass Index; D001831:Body Temperature; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002153:Calorimetry, Indirect; D004041:Dietary Fats; D004435:Eating / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D004041:Dietary Fats; C506876:PNRC2 protein, mouse; D015534:Trans-Activators