NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity.

Autor: Cheng W; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. wenwenc@umich.edu., Ndoka E; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Maung JN; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Pan W; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Rupp AC; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Rhodes CJ; Research and Early Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Olson DP; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.; Division of Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA., Myers MG Jr; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. mgmyers@umich.edu.; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. mgmyers@umich.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Aug 30; Vol. 12 (1), pp. 5175. Date of Electronic Publication: 2021 Aug 30.
DOI: 10.1038/s41467-021-25525-3
Abstrakt: Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; Calcr NTS cells) contribute to the long-term control of food intake and body weight. Here, we show that Prlh-expressing NTS (Prlh NTS ) neurons represent a subset of Calcr NTS cells and that Prlh expression in these cells restrains body weight gain in the face of high fat diet challenge in mice. To understand the relationship of Prlh NTS cells to hypothalamic feeding circuits, we determined the ability of Prlh NTS -mediated signals to overcome enforced activation of AgRP neurons. We found that Prlh NTS neuron activation and Prlh overexpression in Prlh NTS cells abrogates AgRP neuron-driven hyperphagia and ameliorates the obesity of mice deficient in melanocortin signaling or leptin. Thus, enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity, demonstrating that NTS-mediated signals can override the effects of orexigenic hypothalamic signals on long-term energy balance.
(© 2021. The Author(s).)
Databáze: MEDLINE
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