A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism

Yanlin He, Gang Shu, Yongjie Yang, Pingwen Xu, Yan Xia, Chunmei Wang, Kenji Saito, Antentor Hinton, Xiaofeng Yan, Chen Liu, Qi Wu, Qingchun Tong, Yong Xu

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1807-1818
Number of pages12
JournalCell Reports
Volume17
Issue number7
DOIs
StatePublished - Nov 8 2016

Keywords

  • AgRP/NPY neurons
  • body weight
  • energy expenditure
  • food intake
  • SK3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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