Effects of nutritional status and aging on leptin gene expression in mice: importance of glucose.

The factors regulating leptin mRNA under physiological conditions have not been fully elucidated, although both insulin and glucose have been implicated. Since, in male mice, plasma glucose decreases with age without a change in body weight or insulin, aging mice constitute a model to examine effects of glucose independent of effects of insulin or body weight. Therefore, we measured leptin mRNA in adipose tissue of 6-, 15- and 24-month-old C57BL/6J male mice, sacrificed either after a 48 h fast (nutritional deprivation) or 15 min after an intraperitoneal injection of glucose (2 mg/g body weight) (nutritional stimulation). There was a significant effect of both age and nutritional status on leptin mRNA, correlated with effects of age and nutritional status on plasma glucose. Leptin mRNA correlated with body weight, plasma glucose and plasma insulin. After statistically removing effects of plasma glucose, the remaining effects of age, nutritional status, and plasma insulin on leptin mRNA were no longer significant. However, after statistically removing effects of plasma insulin, the remaining effects of age, nutritional status, and plasma glucose continued to be significant. When nutrition-deprived and nutrition-stimulated mice were analyzed separately, plasma glucose significantly correlated with leptin mRNA in both groups, but body weight and plasma insulin correlated with leptin mRNA only in nutrition-deprived mice. When mice at each age were analyzed separately, glucose correlated with leptin mRNA at every age, and after statistical removal of the effects of glucose, the remaining effects of insulin on leptin mRNA were no longer significant at any age. These results support the hypothesis that plasma glucose is important in the regulation of leptin gene expression.