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

ABSTRACT: 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.

SUBMITTER: Cheng W

PROVIDER: S-EPMC8405610 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Cheng Wenwen W Ndoka Ermelinda E Maung Jessica N JN Pan Warren W Rupp Alan C AC Rhodes Christopher J CJ Olson David P DP Myers Martin G MG

Nature communications 20210830 1

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 circ ...[more]

PMID: 34462445

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Project description:BackgroundRecent studies showed that eating behaviors such as disinhibition, emotional and external eating, and snacking mediate genetic susceptibility to obesity. It remains unknown if diet quality and intake of specific food groups also mediate the genetic susceptibility to obesity.ObjectiveThis study aimed to assess if diet quality and intakes of specific food groups mediate the association between a polygenic risk score (PRS) for BMI and BMI and waist circumference (WC). We hypothesized that poor diet quality, high intakes of energy-dense food groups, and low intakes of nutrient-dense food groups mediate the genetic susceptibility to obesity.MethodsThis cross-sectional study included 750 participants (56.3% women, aged 41.5 ± 14.9 y, BMI 27.8 ± 7.5 kg/m2) from the Quebec Family Study. A PRSBMI based on >500,000 genetic variants was calculated using LDpred2. Dietary intakes were assessed with a 3-d food record from which a diet quality score (i.e. Nutrient Rich Food Index 6.3) and food groups were derived. Mediation analyses were conducted using a regression-based and bootstrapping approach.ResultsThe PRSBMI explained 25.7% and 19.8% of the variance in BMI and WC, respectively. The association between PRSBMI and BMI was partly mediated by poor diet quality (β = 0.33 ± 0.12; 95% CI: 0.13, 0.60), high intakes of fat and high-fat foods (β = 0.46 ± 0.16; 95% CI: 0.19, 0.79) and sugar-sweetened beverages (β = 0.25 ± 0.14; 95% CI: 0.05, 0.60), and low intakes of vegetables (β = 0.15 ± 0.08; 95% CI: 0.03, 0.32), fruits (β = 0.37 ± 0.12; 95% CI: 0.17, 0.64), and dairy products (β = 0.17 ± 0.09; 95% CI: 0.02, 0.37). The same trends were observed for WC.ConclusionsThe genetic susceptibility to obesity was partly mediated by poor diet quality and intakes of specific food groups. These results suggest that improvement in diet quality may reduce obesity risk among individuals with high genetic susceptibility and emphasize the need to intervene on diet quality among these individuals.

Dataset Information

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

Publications

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

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