Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipose Tissue / cytology
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Adipose Tissue / metabolism*
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Animals
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Body Weight / genetics*
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Cells, Cultured
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Cyclic AMP / metabolism
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Diglycerides / metabolism
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Enzyme Activation
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Female
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GTP-Binding Proteins / genetics*
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Inositol 1,4,5-Trisphosphate / metabolism
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Lipolysis
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Male
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Mice
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Mice, Transgenic
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Phosphoenolpyruvate Carboxykinase (GTP) / genetics
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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RNA, Antisense / biosynthesis*
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Type C Phospholipases / metabolism
Substances
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Diglycerides
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RNA, Antisense
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Inositol 1,4,5-Trisphosphate
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Cyclic AMP
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Protein Kinase C
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Type C Phospholipases
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GTP-Binding Proteins
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Phosphoenolpyruvate Carboxykinase (GTP)