Author
ZHU, CANJUN - University Of Texas Health Science Center | |
JIANG, ZHIYING - University Of Texas Health Science Center | |
XU, YUANGZHONG - University Of Texas Health Science Center | |
CAI, ZHAO-LIN - Baylor College Of Medicine | |
JIANG, QINGYAN - South China Agricultural University | |
XU, YONG - Children'S Nutrition Research Center (CNRC) | |
XUE, MINGSHAN - Baylor College Of Medicine | |
ARENKIEL, BENJIAMIN - Baylor College Of Medicine | |
WU, QI - Children'S Nutrition Research Center (CNRC) | |
SHU, GANG - South China Agricultural University | |
LU, YUNGANG - University Of Texas Health Science Center | |
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., Lu, Y., Tong, Q. 2020. Profound and redundant functions of arcuate neurons in obesity development. Nature Metabolism. 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. These findings may provide a neurobiological basis for why certain population are prone to develop obesity but hard to reduce their overall 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. |