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Publication : Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake.

First Author  Li Z Year  2015
Journal  Cell Metab Volume  22
Issue  6 Pages  1059-67
PubMed ID  26655697 Mgi Jnum  J:235897
Mgi Id  MGI:5803922 Doi  10.1016/j.cmet.2015.10.012
Citation  Li Z, et al. (2015) Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake. Cell Metab 22(6):1059-67
abstractText  In this report we evaluated the functions of hypothalamic amylin in vivo and in vitro. Profiling of hypothalamic neurons revealed that islet amyloid polypeptide (Iapp, precursor to amylin) is expressed in neurons in the lateral hypothalamus, arcuate nucleus, medial preoptic area, and elsewhere. Hypothalamic expression of lapp is markedly decreased in ob/ob mice and normalized by exogenous leptin. In slices, amylin and leptin had similar electrophysiologic effects on lateral hypothalamic leptin receptor ObRb-expressing neurons, while the amylin antagonist AC187 inhibited their activity and blunted the effect of leptin. Finally, i.c.v. infusion of AC187 acutely reduced the anorectic effects of leptin. These data show that hypothalamic amylin is transcriptionally regulated by leptin, that it can act directly on ObRb neurons in concert with leptin, and that it regulates feeding. These findings provide a potential mechanism for the increased efficacy of a metreleptin/pramlintide combination therapy for obesity.
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