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

Wenwen Cheng (), Ermelinda Ndoka, Jessica N. Maung, Warren Pan, Alan C. Rupp, Christopher J. Rhodes, David P. Olson and Martin G. Myers ()
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Wenwen Cheng: University of Michigan
Ermelinda Ndoka: University of Michigan
Jessica N. Maung: University of Michigan
Warren Pan: University of Michigan
Alan C. Rupp: University of Michigan
Christopher J. Rhodes: Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca
David P. Olson: University of Michigan
Martin G. Myers: University of Michigan

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; CalcrNTS cells) contribute to the long-term control of food intake and body weight. Here, we show that Prlh-expressing NTS (PrlhNTS) neurons represent a subset of CalcrNTS 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 PrlhNTS cells to hypothalamic feeding circuits, we determined the ability of PrlhNTS-mediated signals to overcome enforced activation of AgRP neurons. We found that PrlhNTS neuron activation and Prlh overexpression in PrlhNTS 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25525-3

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DOI: 10.1038/s41467-021-25525-3

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