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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #385609
Research Project: Molecular, Cellular, and Regulatory Aspects of Obesity Development

Location: Children's Nutrition Research Center

Title: Paraventricular hypothalamus mediates diurnal rhythm of metabolism

Author
item KIM, EUR RAN - University Of Texas Health Science Center
item XU, YUANZHONG - University Of Texas Health Science Center
item CASSIDY, RYAN - University Of Texas Health Science Center
item LU, YUNGANG - University Of Texas Health Science Center
item YANG, YONGJIE - Children'S Nutrition Research Center (CNRC)
item TIAN, JINBIN - University Of Texas Health Science Center
item LI, DE-PEI - Md Anderson Cancer Center
item DRUNEN, RACHEL - University Of Texas Health Science Center
item RIBAS-LATRE, ALEIX - University Of Texas Health Science Center
item CAI, ZHAO-LIN - Baylor College Of Medicine
item XUE, MINGSHAN - Baylor College Of Medicine
item ARENKIEL, BEN - Baylor College Of Medicine
item ECKEL-MAHAN, KRISTIN - University Of Texas Health Science Center
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item TONG, QINGCHUN - University Of Texas Health Science Center

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/9/2020
Publication Date: 7/30/2020
Citation: Kim, E., Xu, Y., Cassidy, R., Lu, Y., Yang, Y., Tian, J., Li, D., Drunen, R., Ribas-Latre, A., Cai, Z., Xue, M., Arenkiel, B., Eckel-Mahan, K., Xu, Y., Tong, Q. 2020. Paraventricular hypothalamus mediates diurnal rhythm of metabolism. Nature Communications. 11:3794. https://doi.org/10.1038/s41467-020-17578-7.
DOI: https://doi.org/10.1038/s41467-020-17578-7

Interpretive Summary: Obesity is serious health issue to our society but the mechanisms for obesity development is still elusive. Here we discovered that a small group of cells within the brain, PVH neurons, regulates diurnal food intake and body weight in animals, which may provide neurobiological mechanisms for obesity development in humans.

Technical Abstract: Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor y2 subunit, and dampening rhythmicity of GABAergic input to the PVH reduces diurnal rhythmicity in metabolism and causes obesity. Finally, BMAL1 deletion blunts PVH neuron responses to external stressors, an effect mimicked by HFD feeding. Thus, BMAL1-driven PVH neuron responsiveness in dynamic activity changes involving rhythmic GABAergic neurotransmission mediates diurnal rhythmicity in metabolism and is implicated in diet-induced obesity.