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Physiological consequences of transient hyperleptinemia during discrete developmental periods on body weight in mice.
Science Translational Medicine ( IF 15.8 ) Pub Date : 2020-01-01 , DOI: 10.1126/scitranslmed.aax6629
Alicja A Skowronski 1 , Charles A LeDuc 1, 2 , Kylie S Foo 1 , Yossef Goffer 1 , Lisa C Burnett 1 , Dieter Egli 1, 2, 3 , Rudolph L Leibel 1, 2
Affiliation  

Leptin plays a role in central nervous system developmental programs and intercurrent physiological processes related to body fat regulation. The timing and neuromolecular mechanisms for these effects are relevant to the prevention and treatment of obesity. Factors implicated in a body weight "set point" including dietary fat, circulating leptin, and other adipokines tend to covary with adiposity and are difficult to disarticulate experimentally. To dissociate leptin effects from adiposity and diet, we created a transgenic mouse in which leptin expression is regulated by doxycycline exposure. Using this system, we investigated the physiological consequences of developmentally-timed transient hyperleptinemia on subsequent adiposity. We evaluated physiological effects of leptin elevation during adulthood (9 to 29 weeks old), "adolescence" (3 to 8 weeks old), and the immediate postnatal period [postnatal days 0 to 22 (P0 to P22)] on long-term adiposity and susceptibility to gain weight on high-fat diet (HFD) fed ad libitum. We found that inducing chronic hyperleptinemia in adult or "adolescent" mice did not alter body weight when excess leptin was discontinued, and upon later exposure to HFD, weight gain did not differ from controls. However, transient elevation of circulating leptin from P0 to P22 increased weight and fat gain in response to HFD, indicating greater susceptibility to obesity as adults. Thus, transient plasma leptin elevations-mimicking one aspect of transient adiposity-increased later susceptibility to diet-induced obesity, although these effects were restricted to a critical developmental (P0 to P22) time window. These findings may have clinical implications for weight management in infancy.

中文翻译:

离散发育期短暂性高瘦素血症对小鼠体重的生理影响。

瘦素在中枢神经系统发育程序和与体内脂肪调节相关的并发生理过程中起作用。这些作用的时机和神经分子机制与肥胖症的预防和治疗有关。与体重“设定点”有关的因素包括饮食脂肪,循环瘦素和其他脂肪因子倾向于与肥胖共存,并且在实验中难以区分。为了从肥胖和饮食中分离瘦素的作用,我们创建了一个转基因小鼠,其中瘦素的表达受到强力霉素暴露的调节。使用该系统,我们调查了发育定时的短暂性高瘦素血症对随后肥胖的生理影响。我们评估了成年期(9至29周龄)瘦素升高的生理影响,“
更新日期:2020-01-02
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