Molecular mechanisms for hormonal control of adipose tissue lipolysis.
The fast-acting lipolytic hormones and insulin regulate adipose tissue lipolysis through control of the activity of hormone-sensitive lipase. This enzyme catalyzes the rate limiting step of adipose tissue lipolysis--the hydrolysis of stored triacylglycerols. The isolated enzyme is rapidly phosphorylated and activated by cyclic AMP-dependent protein kinase, with 1 mol of phosphate incorporated per mol of lipase Mr = 84000 subunit into a single serine residue. The enzyme is dephosphorylated and deactivated by protein phosphatases type 1, 2A and 2C. In the intact, isolated adipocytes the enzyme incorporates phosphate in the absence of hormonal stimulation into a specific 'basal' phosphorylation site. The phosphorylation of this 'basal' site (into a serine residue) is not accompanied with any change of the activity of the enzyme and is not influenced by hormones. The fast-acting lipolytic hormones induce a phosphorylation of another serine residue in a 'regulatory' phosphorylation site, which is identical to that phosphorylated in the isolated enzyme by cyclic AMP-dependent protein kinase. Following the phosphorylation of the 'regulatory' site the activity of the lipase, and consequently the rate of lipolysis, is increased almost 50-fold. Insulin causes a rapid net dephosphorylation of the lipase and exerts its well-known anti-lipolytic action. Half-maximal inhibition of both phosphorylation and activity occurs at an insulin concentration of about 25 pM. The mechanism(s) whereby insulin causes its effects is unknown but apparently to a large extent involve reduction of the cellular cyclic AMP level.
D000273:Adipose Tissue / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D006728:Hormones / Q000502:physiology*; D007328:Insulin / Q000502:physiology; D007700:Kinetics; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D008954:Models, Biological; D008970:Molecular Weight; D009638:Norepinephrine / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D006728:Hormones; D007328:Insulin; D014280:Triglycerides; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D000242:Cyclic AMP; D011494:Protein Kinases; D008049:Lipase; D010749:Phosphoprotein Phosphatases; D009638:Norepinephrine