论文部分内容阅读
Leptin regulates energy balance and glucose metabolism via activation of multiple signaling cascades mediated by the long form leptin receptor Ob-Rb.However, the whole spectrum of signaling actions through the three cytoplasmic tyrosines of mouse Ob-Rb remains to be completely defined in vivo.Here we generated two knock-in lines of mice expressing mutant leptin receptors with phenylalanine substitution for all three tyrosines (Y123F) or for Tyrl138 alone (Y3F).Y123F animals developed similarly overt obesity as Y3F animals with abrogated hypothalamic activation of STAT3 by leptin, but exhibited more severe impairment in glucose tolerance.In striking contrast to db/db mice, however, both Y 123F and Y3F mice showed attenuated adiposity with reduced hyperphagia, marked improvement in physical activity and adaptive thermogenesis, as well as significantly ameliorated glycemic control.