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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #340622
Title: A small potassium current in AgRP/NPY neurons regulates feeding behavior and enery metabolism

Author
item HE, YANLIN - Children'S Nutrition Research Center (CNRC)
item SHU, GANG - Children'S Nutrition Research Center (CNRC)
item XU, PINGWEN - Children'S Nutrition Research Center (CNRC)
item YANG, YONGJIE - Children'S Nutrition Research Center (CNRC)
item XIA, YAN - Children'S Nutrition Research Center (CNRC)
item WANG, CHUNMEI - Children'S Nutrition Research Center (CNRC)
item SAITO, KENJI - Children'S Nutrition Research Center (CNRC)
item HINTON, ANTENTOR - Children'S Nutrition Research Center (CNRC)
item YAN, XIAOFENG - Children'S Nutrition Research Center (CNRC)
item LIU, CHEN - University Of Texas Southwestern Medical Center
item WU, QI - Children'S Nutrition Research Center (CNRC)
item TONG, QINGCHUN - University Of Texas Health Science Center
item XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Cell Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/13/2016
Publication Date: 11/8/2016
Citation: He, Y., Shu, G., Xu, P., Yang, Y., Xia, Y., Wang, C., Saito, K., Hinton, A., Yan, X., Liu, C., Wu, Q., Tong, Q., Xu, Y. 2016. A small potassium current in AgRP/NPY neurons regulates feeding behavior and enery metabolism. Cell Reports. 17:1807-1818.

Interpretive Summary: Obesity is a serious global health problem. using a mouse model, ,jwe showed that ion channel, namely SK3, can decrease body weight via its actions in the brain. These findings suggest that SK3 in the brain could be a potential target for treatment of obesity.

Technical Abstract: Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals' feeding behavior and energy metabolism.