Children’s Nutrition Research Center Staff Publications
Publication Date
1-1-2021
Journal
Endocrinology
DOI
10.1210/endocr/bqaa183
PMID
33034617
PMCID
PMC7685027
PubMedCentral® Posted Date
10-9-2020
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Dorsal Raphe Nucleus, Energy Metabolism, Estradiol, Female, Gene Expression Regulation, Genes, fos, Male, Mice, Mice, Knockout, Neurons, Ovariectomy, Sex Factors, Tryptophan Hydroxylase, Weight Gain, TPH2, DRN, food intake, body weight, OVX, E2
Abstract
AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female mice. Ablation of TPH2 reduces hypothalamic pro-opiomelanocortin (POMC) neuronal activity robustly in males, but only to a modest degree in females. Deprivation of estrogen by ovariectomy (OVX) causes comparable food intake and weight gain in female control and DRN-specific TPH2 knockout mice. Nevertheless, disruption of TPH2 blunts the anorexigenic effects of exogenous estradiol (E2) and abolishes E2-induced activation of POMC neurons in OVX female mice, indicating that TPH2 is indispensable for E2 to activate POMC neurons and to suppress appetite. Together, our study revealed that TPH2 in the DRN contributes to energy balance regulation in a sexually dimorphic manner.
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