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.