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. 1993 Nov 1;295(Pt 3):731–734. doi: 10.1042/bj2950731

Diurnal patterns of cardiac and hepatic pyruvate dehydrogenase complex activity in gold-thioglucose-obese mice.

J M Bryson 1, G J Cooney 1, V R Wensley 1, S C Blair 1, I D Caterson 1
PMCID: PMC1134621  PMID: 8240285

Abstract

The diurnal pattern of the activity of the pyruvate dehydrogenase complex (PDHC) was studied in the heart and liver of gold-thioglucose (GTG)-obese mice and age-matched controls. The diurnal pattern of lipogenesis was also measured in the liver. Both lean and obese mice had one main 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 serum 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-obese mice were hyperglycaemic, hyperinsulinaemic and hypertriglyceridaemic at all times studied, with significant increases in these parameters 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. Hepatic PDHC activity was significantly higher in GTG-obese mice at all times except 16:00 h. The simultaneous rise of hepatic PDHC activity, lipogenesis and serum triacylglycerols in GTG-obese mice suggests an increased utilization of glucose for lipogenesis. The lack of change in heart PDHC activity in GTG-obese mice over 24 h suggests that a general decrease in PDHC activity may contribute to the development of the glucose intolerance and insulin resistance of obesity and non-insulin-dependent diabetes. However, it appears that a different level of metabolic control allows hepatic PDHC activity of the same obese animals to increase in response to hyperinsulinaemia and contribute to the higher rates of lipogenesis seen in obese mice.

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Selected References

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  1. Caterson I. D., Astbury L. D., Williams P. F., Vanner M. A., Cooney G. J., Turtle J. R. The activity of the pyruvate dehydrogenase complex in heart and liver from mice during the development of obesity and insulin resistance. Biochem J. 1987 Apr 15;243(2):549–553. doi: 10.1042/bj2430549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caterson I. D., Kerbey A. L., Cooney G. J., Frankland R., Denyer G. S., Nicks J., Williams P. F. Inactivation of pyruvate dehydrogenase complex in heart muscle mitochondria of gold-thioglucose-induced obese mice is not due to a stable increase in activity of pyruvate dehydrogenase kinase. Biochem J. 1988 Jul 1;253(1):291–294. doi: 10.1042/bj2530291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caterson I. D., Williams P. F., Kerbey A. L., Astbury L. D., Plehwe W. E., Turtle J. R. The effect of body weight and the fatty acid-oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in mouse heart. Biochem J. 1984 Dec 15;224(3):787–791. doi: 10.1042/bj2240787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen C., Williams P. F., Cooney G. J., Caterson I. D., Turtle J. R. The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice. Horm Metab Res. 1992 Apr;24(4):161–166. doi: 10.1055/s-2007-1003285. [DOI] [PubMed] [Google Scholar]
  5. Cooney G. J., Astbury L. D., Williams P. F., Caterson I. D. Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose. Diabetes. 1987 Feb;36(2):152–158. doi: 10.2337/diab.36.2.152. [DOI] [PubMed] [Google Scholar]
  6. Cooney G. J., Denyer G. S., Jenkins A. B., Storlien L. H., Kraegen E. W., Caterson I. D. In vivo insulin sensitivity of the pyruvate dehydrogenase complex in tissues of the rat. Am J Physiol. 1993 Jul;265(1 Pt 1):E102–E107. doi: 10.1152/ajpendo.1993.265.1.E102. [DOI] [PubMed] [Google Scholar]
  7. Cooney G. J., Denyer G. S., Kerbey A. L., Frankland R. L., Blair S. C., Williams P. F., Caterson I. D. Pyruvate dehydrogenase-complex activity in brown adipose tissue of gold thioglucose-obese mice. Biochem J. 1990 Aug 15;270(1):257–259. doi: 10.1042/bj2700257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooney G. J., Vanner M. A., Nicks J. L., Williams P. F., Caterson I. D. Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold-thioglucose-injected mouse. Biochem J. 1989 May 1;259(3):651–657. doi: 10.1042/bj2590651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Denyer G. S., Cooney G. J., Storlien L. H., Jenkins A. B., Kraegen E. W., Kusunoki M., Caterson I. D. Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex. Pflugers Arch. 1991 Sep;419(2):115–120. doi: 10.1007/BF00372995. [DOI] [PubMed] [Google Scholar]
  10. Denyer G. S., Lam D., Cooney G. J., Caterson I. D. Effect of starvation and insulin in vivo on the activity of the pyruvate dehydrogenase complex in rat skeletal muscles. FEBS Lett. 1989 Jul 3;250(2):464–468. doi: 10.1016/0014-5793(89)80777-x. [DOI] [PubMed] [Google Scholar]
  11. Kerbey A. L., Randle P. J., Cooper R. H., Whitehouse S., Pask H. T., Denton R. M. Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. Biochem J. 1976 Feb 15;154(2):327–348. doi: 10.1042/bj1540327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Le Marchand-Brustel Y., Grémeaux T., Ballotti R., Van Obberghen E. Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice. Nature. 1985 Jun 20;315(6021):676–679. doi: 10.1038/315676a0. [DOI] [PubMed] [Google Scholar]
  13. McGarry J. D., Foster D. W. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem. 1980;49:395–420. doi: 10.1146/annurev.bi.49.070180.002143. [DOI] [PubMed] [Google Scholar]
  14. RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
  15. Randle P. J., Kerbey A. L., Espinal J. Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones. Diabetes Metab Rev. 1988 Nov;4(7):623–638. doi: 10.1002/dmr.5610040702. [DOI] [PubMed] [Google Scholar]
  16. Sugden M. C., Howard R. M., Holness M. J. Variations in hepatic carbon flux during unrestricted feeding. Biochem J. 1992 Jun 15;284(Pt 3):721–724. doi: 10.1042/bj2840721. [DOI] [PMC free article] [PubMed] [Google Scholar]

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