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

Cell Rep. 2016 Nov 8;17(7):1807-1818. doi: 10.1016/j.celrep.2016.10.044.


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.

Keywords: AgRP/NPY neurons; SK3; body weight; energy expenditure; food intake.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Agouti-Related Protein / metabolism*
  • Animals
  • Circadian Rhythm / drug effects
  • Diet, High-Fat
  • Energy Metabolism* / drug effects
  • Fasting / metabolism
  • Feeding Behavior* / drug effects
  • Hyperphagia / complications
  • Hyperphagia / metabolism
  • Ion Channel Gating / drug effects
  • Mice, Inbred C57BL
  • Mutation / genetics
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism*
  • Obesity / complications
  • Obesity / metabolism
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism*


  • Agouti-Related Protein
  • Neuropeptide Y
  • Small-Conductance Calcium-Activated Potassium Channels
  • N-Methylaspartate