Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Mol Metab. 2014 Mar 5;3(4):432-40. doi: 10.1016/j.molmet.2014.02.003. eCollection 2014 Jul.
Circulating leptin concentrations correlate with fat mass and signal the status of somatic energy stores to the brain. Previous studies suggest that diet-induced elevations of body weight increase body weight "set-point". To assess whether chronic hyperleptinemia is responsible for this shift in defended body weight, we elevated circulating leptin concentrations in lean mice to those comparable to diet-induced obese mice for eighteen weeks. We hypothesized that following cessation of leptin infusion, a higher body weight would be defended. Compared to saline-infused controls, leptin-infused mice had elevated circulating leptin concentrations, gained less weight, yet had similar metabolic rates. Following cessation of leptin administration, leptin-infused mice gained some weight yet plateaued at 5-10% below controls. These results suggest that, unlike mice rendered hyperleptinemic by diet-induced weight gain, leptin-infused mice do not subsequently "defend" a higher body weight, suggesting that hyperleptinemia per se does not mimic the CNS consequences of chronic weight gain.
循环瘦素浓度与脂肪量相关，并向大脑发出体脂储存状态的信号。先前的研究表明，饮食诱导的体重增加会增加体重“设定点”。为了评估慢性高瘦素血症是否是导致这种防御性体重变化的原因，我们将瘦鼠的循环瘦素浓度升高到与饮食诱导肥胖鼠相当的水平长达十八周。我们假设，在停止瘦素输注后，会有更高的体重被防御。与盐水输注对照组相比，瘦素输注组的循环瘦素浓度升高，体重增加较少，但代谢率相似。停止瘦素给药后，瘦素输注组的体重有所增加，但在对照组的 5-10%以下达到平台期。这些结果表明，与因饮食诱导体重增加而导致的高瘦素血症的小鼠不同，瘦素输注组随后不会“防御”更高的体重，这表明高瘦素血症本身并不会模拟慢性体重增加对中枢神经系统的影响。
