DIURNAL PATTERNS OF CARDIAC AND HEPATIC PYRUVATE-DEHYDROGENASE COMPLEX ACTIVITY IN GOLD THIOGLUCOSE-OBESE MICE

The diurnal pattern of the activity of the pyruvate dehydrogenase comp lex (PDHC) was studied in the heart and liver of gold-thioglucose (GTG )-obese mice and age-matched controls. The diurnal pattern of lipogene sis was also measured in the liver. Both lean and obese mice had one m ain eating period, from 20: 00 to 24: 00 h. Eating produced no change in serum glucose of control mice but there was a significant rise in s erum insulin and triacylglycerols. There was also a 3-fold increase in cardiac PDHC activity and a 3-fold increase in hepatic lipogenesis in the control mice, but little change in hepatic PDHC activity. GTG-obe se mice were hyperglycaemic, hyperinsulinaemic and hyper-triglyceridae mic at all times studied, with significant increases in these paramete rs being seen in response to eating. Eating produced little change in cardiac PDHC activity, but there was a 5-fold increase in hepatic PDHC activity, paralleled by a 10-fold increase in hepatic lipogenesis. He patic PDHC activity was significantly higher in GTG-obese mice at all times except 16:00h. The simultaneous rise of hepatic PDHC activity, l ipogenesis and serum triacylglycerols in GTG-obese mice suggests an in creased utilization of glucose for lipogenesis. The lack of change in heart PDHC activity in GTG-obese mice over 24 h suggests that a genera l decrease in PDHC activity may contribute to the development of the g lucose intolerance and insulin resistance of obesity and non-insulin-d ependent diabetes. However, it appears that a different level of metab olic control allows hepatic PDHC activity of the same obese animals to increase in response to hyperinsulinaemia and contribute to the highe r rates of lipogenesis seen in obese mice.