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 language | English (US) |
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Pages (from-to) | 1807-1818 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 17 |
Issue number | 7 |
DOIs | |
State | Published - Nov 8 2016 |
Keywords
- AgRP/NPY neurons
- SK3
- body weight
- energy expenditure
- food intake
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology