Induction of G alpha(q)-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 G alpha(q) provide a model in which to study a loss-of-function mutant of G alpha(q) in vivo. G alpha(q) 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. G alpha(q)-deficient adipocytes display reduced lipolytic responses, shown to reflect a newly discovered, alpha(1)-adrenergic regulation of lipolysis. This alpha(1)-adrenergic response via phosphoinositide hydrolysis and activation of protein kinase C is lacking in the G alpha(q) loss-of-function mutants in vivo and provides a basis for the increased fat accumulation.