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Experiments were performed to investigate the timing of the development of hyperleptinemia with that of hyperinsulinemia in the gold thioglucose-injected (GTG) mouse. The relationships between the circulating leptin levels and the size of fat deposits during the development of obesity among fasted and fed mice and the effect of glucocorticoid decrease on the amount of leptin circulating in the blood were examined. The findings demonstrated increased obesity gene expression preceded by hyperinsulinemia.

The activity of the pyruvate dehydrogenase complex (PDHC), as an indicator of glucose oxidation in tissues of controls, showed that changes in PDHC activity induced significantly short-term increases in plasma insulin within the physiological range in insulin resistant fat-fed rats. It is proven that the regulation of intracellular glucose oxidation depends on the local intracellular fatty acid metabolism.

Bryson, Janet M., Jenny L. Phuyal, Verity Swan, and Ian D. Caterson. Leptin has acute effects on glucose and lipid metabolism in both lean and gold thioglucose-obese mice. Am. J. Physiol. 277 (Endocrinol. Metab. 40): E417-E422, 1999.--Leptin is reported to have effects in peripheral tissues that are independent of its central effects on food intake and body weight. In this study, the acute effects of a single dose of recombinant mouse leptin on lipid and glucose metabolism in lean and gold thioglucose-injected obese mice were examined. Changes were measured 2 h after leptin injection. In lean mice, liver and white adipose tissue (WAT) lipogenesis was inhibited. The activity of the pyruvate dehydrogenase complex (PDHCa), the rate-determining step for glucose oxidation, was reduced in heart, liver, quadriceps muscle, and both brown and white adipose tissues. Muscle and liver glycogen and liver triglyceride (TG) content was unchanged, but muscle TG was decreased. In obese mice, liver and WAT lipogenesis was inhibited and PDHCa reduced in heart and quadriceps muscle. Muscle and liver glycogen was decreased but not TG. Serum insulin was reduced in obese but not lean mice. These results are consistent with a role for leptin in the maintenance of steady-state energy stores by decreasing lipid synthesis and increasing fat mobilization, with decreased glucose oxidation occurring as a result of increased fatty acid oxidation. lipogenesis; pyruvate dehydrogenase complex; fatty acid oxidation