Cold-induced beta-adrenergic recruitment of lipoprotein lipase in brown fat is due to increased transcription.
The cellular basis for the cold-induced increase in lipoprotein lipase activity in rat brown adipose tissue was investigated. Rats were treated with inhibitory agents and either exposed to cold for 4 h or injected with isoprenaline. Lipoprotein lipase activity was followed in acetone-ether extracts of the tissue. Besides cold, both the beta-adrenergic agonist isoprenaline and the adenylate cyclase activator cholera toxin were able to increase lipoprotein lipase activity in the tissue. The protein synthesis inhibitor cycloheximide fully abolished this response; the half-life of lipoprotein lipase activity was both in control and in the cold-exposed state approximately 2 h. Also the mRNA synthesis inhibitor actinomycin D fully abolished the cold-, the isoprenaline-, and the cholera toxin-induced increases in lipoprotein lipase activity; the half-life of lipoprotein lipase mRNA was estimated to be 20-30 h. However, in animals returned to control conditions after a 4-h cold stress, the decline in activity corresponded to a half-life of only 4 h. It was concluded that the increase in lipoprotein lipase activity in the brown adipose tissue of cold-exposed rats is not due to an activation of preexisting enzyme nor due to an increased half-life of functional enzyme. Rather it is suggested that in brown adipose tissue the rate of lipoprotein lipase gene transcription is positively regulated by the cellular level of cAMP and that this increase in lipoprotein lipase mRNA leads directly to an increased rate of enzyme synthesis and hence to the increase in activity.
D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000818:Animals; D003080:Cold Temperature; D000242:Cyclic AMP / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D012313:RNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D003609:Dactinomycin; D012313:RNA; D000242:Cyclic AMP; D008071:Lipoprotein Lipase