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Physiological consequences of transient hyperleptinemia during discrete developmental periods on body weight in mice.

ABSTRACT: 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.

SUBMITTER: Skowronski AA

PROVIDER: S-EPMC7427106 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Physiological consequences of transient hyperleptinemia during discrete developmental periods on body weight in mice.

Skowronski Alicja A AA LeDuc Charles A CA Foo Kylie S KS Goffer Yossef Y Burnett Lisa C LC Egli Dieter D Leibel Rudolph L RL

Science translational medicine 20200101 524

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 d ...[more]

PMID: 31894105

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Physiological consequences of transient hyperleptinemia during discrete developmental periods on body weight in mice.

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Physiological consequences of transient hyperleptinemia during discrete developmental periods on body weight in mice.

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