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Unraveling the central nervous system pathways underlying responses to leptin

Abstract

Here we summarize recent progress in the biology of leptin, concentrating on its central nervous system (CNS) actions. The product of the ob gene, leptin is a circulating hormone produced by white adipose tissue that has potent effects on feeding behavior, thermogenesis and neuroendocrine responses. Leptin regulates energy homeostasis, as its absence in rodents and humans causes severe obesity. We consider the physiological mechanisms underlying leptin action, along with several novel hypothalamic neuropeptides that affect food intake and body weight. The molecular causes of several other obesity syndromes are discussed to illuminate how the CNS regulates body weight. We describe neural circuits that are downstream of leptin receptors and propose a model linking populations of leptin-responsive neurons with effector neurons underlying leptin's endocrine, autonomic and behavioral effects.

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Figure 1: Hypothalamic cell groups respond to circulating leptin.
Figure 2: A neuroanatomical model of leptin's actions in the rat brain.

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Acknowledgements

The authors thank Quan Ha, Minh Ha, Charlotte Lee and Joseph Kelly for technical assistance and Carol Elias, Christian Bjørbæk and Rexford S. Ahima for discussions.

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Elmquist, J., Maratos-Flier, E., Saper, C. et al. Unraveling the central nervous system pathways underlying responses to leptin. Nat Neurosci 1, 445–450 (1998). https://doi.org/10.1038/2164

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