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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #386010
Research Project: Molecular, Cellular, and Regulatory Aspects of Obesity Development

Location: Children's Nutrition Research Center

Title: Profound and redundant functions of arcuate neurons in obesity development

Author
item ZHU, CANJUN - University Of Texas Health Science Center
item JIANG, ZHIYING - University Of Texas Health Science Center
item XU, YUANGZHONG - University Of Texas Health Science Center
item CAI, ZHAO-LIN - Baylor College Of Medicine
item JIANG, QINGYAN - South China Agricultural Univerisity
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item XUE, MINGSHAN - Baylor College Of Medicine
item ARENKIEL, BENJIAMIN - Baylor College Of Medicine
item WU, QI - Children'S Nutrition Research Center (CNRC)
item SHU, GANG - South China Agricultural Univerisity
item TONG, QINGCHUN - University Of Texas Health Science Center

Submitted to: Nature Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2020
Publication Date: 7/27/2020
Citation: Zhu, C., Jiang, Z., Xu, Y., Cai, Z., Jiang, Q., Xu, Y., Xue, M., Arenkiel, B., Wu, Q., Shu, G., Tong, Q. 2020. Profound and redundant functions of arcuate neurons in obesity development. Nature Metabolism. 2:763-774. https://doi.org/10.1038/s42255-020-0229-2.
DOI: https://doi.org/10.1038/s42255-020-0229-2

Interpretive Summary: Obesity is a serious health issue to our society but the mechanisms for obesity development is still elusive. Here we discovered a small group of cells within the brain that drastically increases food intake and body weight, which may provide a neurobiological basis for why certain populations are prone to develop obesity but hchallenged to reduce their weight.

Technical Abstract: The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate GABAergic (GABA+), agouti-related protein (AgRP) neurons or arcuate non-AgRP GABA+neurons leads to obesity, which is similar to the obese phenotype observed in ob/ob mice. Conversely, chronic inhibition of arcuate GABA+, but not AgRP, neurons reduces ageing-related weight gain and corrects ob/ob obesity. These results demonstrate that the modulation of Arc GABA+neuron activity is a fundamental mechanism of body-weight regulation, and that arcuate GABA+neurons are the major mediator of leptin action, with a profound and redundant role in obesity development.