Induction of Galphaq-specific antisense RNA in vivo causes increased body mass and hyperadiposity.
Transgenic BDF-1 mice harboring an inducible, tissue-specific transgene for RNA antisense to Galphaq provide a model in which to study a loss-of-function mutant of Galphaq in vivo. Galphaq deficiency induced in liver and white adipose tissue at birth produced increased body mass and hyperadiposity within 5 weeks of birth that persisted throughout adult life. Galphaq-deficient adipocytes display reduced lipolytic responses, shown to reflect a newly discovered, alpha1-adrenergic regulation of lipolysis. This alpha1-adrenergic response via phosphoinositide hydrolysis and activation of protein kinase C is lacking in the Galphaq loss-of-function mutants in vivo and provides a basis for the increased fat accumulation.
Galvin-Parton
P A
PA
Department of Pediatrics, Diabetes and Metabolic Diseases Research Program, University Medical Center, SUNY/Stony Brook, Stony Brook, New York 11794-8651, USA.
Chen
X
X
Moxham
C M
CM
Malbon
C C
CC
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D016372:RNA, Antisense / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D016372:RNA, Antisense; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D010729:Phosphoenolpyruvate Carboxykinase (GTP)