Steppan C M, Crawford D T, Chidsey-Frink K L, Ke H, Swick A G
Department of Metabolic Diseases, Pfizer Central Research, Eastern Point Road, 06340, Groton, CT, USA.
Regul Pept. 2000 Aug 25;92(1-3):73-8. doi: 10.1016/s0167-0115(00)00152-x.
Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. The lack of leptin in ob/ob mice, who are homozygous for the obese gene, results in hyperglycemia, hyperinsulinemia, hyperphagia, obesity, infertility, decreased brain size and decreased stature. To this end, we investigated the role of leptin as a hormonal regulator of bone growth. Leptin administration led to a significant increase in femoral length, total body bone area, bone mineral content and bone density in ob/ob mice as compared to vehicle treated controls. The increase in total body bone mass was a result of an increase in both trabecular and cortical bone mass. These results suggest that the decreased stature of the ob/ob mouse is due to a developmental defect that is readily reversible upon leptin administration. Our demonstration that the signalling or long form (Ob-Rb) of the leptin receptor is present in both primary adult osteoblasts and chondrocytes suggests that the growth promoting effects of leptin could be direct. In summary, these results indicate a novel role for leptin in skeletal bone growth and development.
瘦素是肥胖基因的产物，是一种主要由脂肪细胞分泌的循环激素。肥胖基因纯合的ob/ob小鼠缺乏瘦素，会导致高血糖、高胰岛素血症、食欲亢进、肥胖、不育、脑体积减小和身材矮小。为此，我们研究了瘦素作为骨生长激素调节剂的作用。与用赋形剂处理的对照组相比，给ob/ob小鼠注射瘦素导致股骨长度、全身骨面积、骨矿物质含量和骨密度显著增加。全身骨量的增加是小梁骨和皮质骨量增加的结果。这些结果表明，ob/ob小鼠身材矮小是由于发育缺陷，而注射瘦素后这种缺陷很容易逆转。我们证明瘦素受体的信号传导形式或长形式（Ob-Rb）存在于原代成年成骨细胞和软骨细胞中，这表明瘦素的促生长作用可能是直接的。总之，这些结果表明瘦素在骨骼生长和发育中具有新的作用。
