Leptin Corrects Increased Gene Expression of Renal 25-Hydroxyvitamin D3-1α-Hydroxylase and -24-Hydroxylase in Leptin-Deficient,ob/obMice
| Autor: | Toyonobu Maeda, Noboru Horiuchi, Tetsuya Kawane, Ayako Matsunuma, Setsuo Hamada |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Leptin
Male medicine.medical_specialty Deoxypyridinoline Mice Obese Biology Kidney Bone and Bones Gene Expression Regulation Enzymologic Bone resorption Bone remodeling Mice chemistry.chemical_compound Endocrinology Calcitriol Cytochrome P-450 Enzyme System Bone Density Internal medicine medicine Animals Homeostasis Vitamin D3 24-Hydroxylase 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Bone mineral Phosphorus Urinary calcium Mice Inbred C57BL medicine.anatomical_structure chemistry Steroid Hydroxylases Alkaline phosphatase Calcium Biomarkers |
| Zdroj: | Endocrinology. 145:1367-1375 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Leptin, the ob gene product secreted by adipocytes, controls overall energy balance. We investigated leptin effects on bone metabolism using male leptin-deficient obese (ob/ob) mice, which had lower bone mineral density (BMD) and shorter femurs than lean (?/+) controls. Serum concentrations of calcium, phosphate, tartrate-resistant acid phosphatase (a bone resorption marker) and alkaline phosphatase, and urinary calcium and phosphate excretion were significantly elevated in ob/ob mice, whereas urinary concentrations of deoxypyridinoline did not differed between ob/ob and control mice. Because ob/ob mice develop severe hypogonadism, testosterone was administered to these mice for 10 wk (5 mg/kg, sc, twice weekly); this did not affect femoral BMD. Control and ob/ob mice showed similar vitamin D-receptor densities in bone and kidney; the obese mice had marked increases in serum 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] and in mRNA expression and activities of renal 25-hydroxyvitamin D(3)-1 alpha-hydroxylase (CYP27B1) and -24-hydroxylase (CYP24) compared with control mice. Leptin administration to ob/ob mice (4 mg/kg body weight, ip, every 12 h for 2 d) greatly reduced mRNAs and activities of 1 alpha-hydroxylase and 24-hydroxylase. Elevated concentrations of serum calcium, phosphate, and 1,25-(OH)(2)D(3) were normalized by leptin treatment. Thus, leptin suppresses renal gene overexpression for 1 alpha-hydroxylase and 24-hydroxylase and corrects increased serum concentrations of calcium and phosphate in ob/ob mice. Therefore, low BMD in leptin-deficient mice appears to be related to stimulation of bone resorption by 1,25-(OH)(2)D(3). |
| Databáze: | OpenAIRE |
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