Inhibition of adenosine 3':k'-monophosphate accumulation white fat acids, lactate, and beta-hydroxybutyrate.
The large increase in cyclic AMP accumulation by rat white fat cells seen in the presence of lipolytic agents plus methylxanthines and adenosine deaminase was markedly inhibited by lactate. However, lipolysis was unaffected by lactate. Octanoate, hexanoate, heptanoate, and beta-hydroxybutyrate inhibited both cyclic AMP accumulation and lipolysis by rat fat cells. The mechanism by which these acids inhibit lipolysis differs from that for long chain fatty acids such as oleate. Oleate directly inhibited triglyceride lipase activity of homogenized rat adipose tissue. In contrast, octanoate, beta-hydroxybutyrate, and lacatate had no effect on triglyceride lipase activity. Hormone-stimulated adenylate cyclase activity of rat fat cell ghosts was inhibited by oleate and 4mM octanoate but not by 1.6 mM octanoate, heptanoate, hexanoate, beta-hydroxybutyrate or lactate. None of the acids affected the soluble protein kinase activity of rat adipose tissue. There was no stimulation by lactate, butyrate, beta-hydroxybutyrate, or octanoate of the soluble or particulate cyclic AMP antilipolytic action of a short chain acid such as octanoate or hexanoate was not accompanied by any drop in total fat cell ATP. The mechanism by which lactate lowers cyclic AMP but not lipolysis remains to be established.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology*; D008053:Lipid Mobilization / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007773:Lactates; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D009638:Norepinephrine