Effect of Leptin on Regulation of Renal 25-hydroxyvitamin D3 Metabolism and Maintenance of Calcium Homeostasis

Leptin, a hormone secreted by adipocytes, acts on the hypothalamus to reduce appetite and inhibit body weight gain. Leptin has pleiotropic actions on bone, gonadal hormone secretion, the pancreas, immune tissues, and vascular organs. Leptin-deficient (ob/ob) mice, used in many studies defining leptin actions, have low bone mineral density (BMD) and retarded femoral growth. Loss of leptin function contributes to aberrant regulation of renal 25-hydroxyvitamin D3 metabolism by increasing the gene expression of renal 1α-hydroxylase, which catalyzes 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] synthesis and thus elevates serum 1,25(OH)2D3 concentrations. Excess 1,25(OH)2D3 results in increased calcium absorption in the intestine and stimulates bone resorption, resulting in reduced BMD, especially in long bones. Finally, leptin deficiency increases serum calcium concentrations; excess calcium in blood is excreted in urine.