Counter modulation of adipocyte mitochondrial processes by insulin and S-oxalylglutathione

• Published in: The international journal of biochemistry & cell biology Vol. 28; no. 2; pp. 183 - 191
• Main Authors: Moore, Kathleen H., Tsatsos, Panagiota, Staudacher, Diane M., Kiechle, Frederick L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-02-1996
• Subjects: Acyl-CoA hydrolase; Adipocytes - drug effects; Adipocytes - metabolism; Adipocytes - ultrastructure; Animals; Enzyme Inhibitors - pharmacology; Epididymis - cytology; Epididymis - drug effects; Epididymis - metabolism; Glutathione - analogs & derivatives; Glutathione - pharmacology; Insulin - pharmacology; Male; Metabolism; Mitochondria - drug effects; Mitochondria - enzymology; Mitochondria - metabolism; Oxalyl thiolesters; Oxidation-Reduction; Palmitoyl-CoA Hydrolase - drug effects; Pyruvate dehydrogenase; Pyruvate Dehydrogenase Complex - drug effects; Rats; Rats, Sprague-Dawley; β-Oxidation; Acyl-CoA hydrolase; Pyruvate dehydrogenase; Oxalyl thiolesters; Metabolism; β-Oxidation
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/1357-2725(95)00132-8

Oxalyl thiolesters, a group of putative intracellular regulators, have been shown to be in vitro inhibitors of some cytosolic enzymes which are stimulated by insulin. In this study, the effects of insulin and oxalyl thiolesters on pyruvate dehydrogenase, β-oxidation, and acyl-CoA hydrolase activities in mitochondria from rat epididymal adipocytes are compared. Using glutathione, CoASH, cysteine, and cysteamine as thiol sources, oxalyl thiolesters were synthesized, purified, and quantitated. Mitochondria were isolated from rat epididymal adipocytes, some of which were incubated with or without insulin. Mitochondrial activities were determined by radio topic assay subsequent to control, insulin, or oxalyl thiolester incubation. Under the conditions used in this may, pyrovate dehydrogenase activity was increased 28% subsequent to 10-min incubation of adipocytes with 400 μU/ml insulin; in contrast, preincubation of adipocyte mitochondria with S-oxalylgintathione resulted in a dose-dependent 11–19% inhibition of pyruvate dehydrogenase. S-oxalyiglutathione also attenuated the spermine-induced activation of pyruvate dehydrogenase. Insulin treatment resulted in a mall but significant increase in β -oxidation of palmitic acid while 100 μM S-oxalylglutathione mediated a 40% decrease in palmitate oxidation. Pahnitoyl-CoA hydrolase activity was decreased 14% by insulin treatment; however, S-oxalylgiutathione caused a 14–50% increase in hydrolaxe activity. The other oxalyl thiolesters were not as effective or as consistent as S-oxalylglutathione in modulation of the mitochondrial activities; free thiols and oxalic acid did not modulate the activities. In summary, pyruvate dehydrogenase, palmitate β-oxidation, and pahnitoyl-CoA hydrolaxe activities in adipocyte mitochondria were modulated in approximately equal but opposite directions by insulin and S-oxalylglutathione. These findings support the suggestion that oxalyl thiolesters may function as an intracellular signal recruited to return insulin to normal levels.