title: Diet composition, not calorie intake, rapidly alters intrinsic excitability of hypothalamic AgRP/NPY neurons in mice.
abstract: Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate acute effects of HFD on AgRP neuronal excitability and highlight a critical role for diet composition. In parallel with our earlier finding in obese, long-term HFD mice, we found that even brief HFD feeding results in persistent activation of ARH AgRP neurons. However, unlike long-term HFD-fed mice, AgRP neurons from short-term HFD-fed mice were still leptin-sensitive, indicating that the development of leptin-insensitivity is not a prerequisite for the increased firing rate of AgRP neurons. To distinguish between diet composition, caloric intake, and body weight, we compared acute and long-term effects of HFD and CD in pair-fed mice on AgRP neuronal spiking. HFD consumption in pair-fed mice resulted in a significant increase in AgRP neuronal spiking despite controls for weight gain and caloric intake. Taken together, our results suggest that diet composition may be more important than either calorie intake or body weight for electrically remodeling arcuate AgRP/NPY neurons.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pham
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Jesse W
authors.initials: JW
authors.lastname: Gammons
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sutherland
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.|College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan City, Hubei Province, China 430065.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Alana
authors.initials: A
authors.lastname: Smith
authors.affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Kaczorowski
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163.
authors.forename: Kristen M S
authors.initials: KM
authors.lastname: O'Connell
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D054369:Agouti-Related Protein / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake; D005786:Gene Expression Regulation; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D004041:Dietary Fats; D020738:Leptin; D009478:Neuropeptide Y