Increased protease activity in muscles of obese- (ob/ob) mice.
Muscles of genetically-obese animals exhibit decreased binding of and metabolic responses to insulin. Muscle protein catabolism was investigated by measuring the activity of alkaline, myofibril-bound protease in male (ob/ob) mice, fed ad libitum, or fasted for 5 d. Enzyme activity in the isolated myobrillar fraction was determined by the degradation of 14C-globin. Compared to the lean siblings, protease activity in the obese mice was 2.0, 1.5 and 1.3-fold higher in gastrocnemius, diaphragm and soleus muscle respectively, but without change in heart. The higher protease activity in gastrocnemius, diaphragm and soleus was associated with a parallel decrease in the weight and protein mass of the muscles. The muscles of obese mice also showed a 3 to 4-fold increase in triglyceride and a 2-fold increase in glycogen content. After 5-d starvation, the activity of protease rose in the gastrocnemius of obese mice only 1.5 fold, while it increased as much as 4 and 2 fold in gastrocnemius and diaphragm, respectively, in the lean mice. There was no significant change in heart enzyme activity. After 5-d starvation, serum insulin in obese mice fell markedly but remained still higher than that in ad libitum fed lean mice. Insulin-dependent serum metabolites, as well as adipose tissue lipoprotein lipase and hepatic enzymes related to lipogenesis and gluconeogenesis were consequently much less affected in obese mice and the prevalence of adequate insulin supply appeared to be the cause for lack of significant effect on muscle protease activity in fasting obese mice. It is suggested, therefore, that the induction of myofibrillar protease in obesity is linked to the decrease in cellular responsiveness to insulin and may also be interrelated with the intracellular metabolic adjustments to the enhanced muscle lipid availability.
D000818:Animals; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D009210:Myofibrils / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D007328:Insulin; D009124:Muscle Proteins; D014280:Triglycerides; D006003:Glycogen; D010447:Peptide Hydrolases