A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.
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.
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yanlin
Y
He
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; College of Animal Science, South China Agricultural University, Guangzhou 100044, China.
Gang
G
Shu
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yongjie
Y
Yang
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Pingwen
P
Xu
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yan
Y
Xia
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Chunmei
C
Wang
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Kenji
K
Saito
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Antentor
A
Hinton
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xiaofeng
X
Yan
Division of Hypothalamic Research, Department of Internal Medical, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Chen
C
Liu
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Qi
Q
Wu
Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Qingchun
Q
Tong
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: yongx@bcm.edu.
Yong
Y
Xu
D000200:Action Potentials / Q000187:drug effects; D054369:Agouti-Related Protein / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D006963:Hyperphagia / Q000150:complications / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*
D054369:Agouti-Related Protein; D009478:Neuropeptide Y; D051640:Small-Conductance Calcium-Activated Potassium Channels; D016202:N-Methylaspartate
AgRP/NPY neurons; SK3; body weight; energy expenditure; food intake