title: Developmental switch of leptin signaling in arcuate nucleus neurons.
abstract: Leptin is well known for its role in the regulation of energy homeostasis in adults, a mechanism that at least partially results from the inhibition of the activity of NPY/AgRP/GABA neurons (NAG) in the arcuate nucleus of the hypothalamus (ARH). During early postnatal development in the rodent, leptin promotes axonal outgrowth from ARH neurons, and preautonomic NAG neurons are particularly responsive to leptin's trophic effects. To begin to understand how leptin could simultaneously promote axonal outgrowth from and inhibit the activity of NAG neurons, we characterized the electrochemical effects of leptin on NAG neurons in mice during early development. Here, we show that NAG neurons do indeed express a functional leptin receptor throughout the early postnatal period in the mouse; however, at postnatal days 13-15, leptin causes membrane depolarization in NAG neurons, rather than the expected hyperpolarization. Leptin action on NAG neurons transitions from stimulatory to inhibitory in the periweaning period, in parallel with the acquisition of functional ATP-sensitive potassium channels. These findings are consistent with the idea that leptin provides an orexigenic drive through the NAG system to help rapidly growing pups meet their energy requirements.
authors: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center, Beaverton, Oregon 97006.
authors: Arian F
authors: AF
authors: Baquero
authors: Division of Molecular Genetics, Naomi Berrie Diabetes Center, Columbia University, New York, New York 10032.
authors: Alain J
authors: http://orcid.org/0000-0002-0181-3287
authors: AJ
authors: de Solis
authors: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center, Beaverton, Oregon 97006.
authors: Sarah R
authors: SR
authors: Lindsley
authors: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center, Beaverton, Oregon 97006.
authors: Melissa A
authors: http://orcid.org/0000-0002-2570-777X
authors: MA
authors: Kirigiti
authors: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center, Beaverton, Oregon 97006.
authors: M Susan
authors: http://orcid.org/0000-0002-3057-7009
authors: MS
authors: Smith
authors: Monash Obesity and Diabetes Institute, Monash University, Clayton, Victoria, Australia 3800, and.
authors: Michael A
authors: MA
authors: Cowley
authors: Division of Molecular Genetics, Naomi Berrie Diabetes Center, Columbia University, New York, New York 10032, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032.
authors: Lori M
authors: http://orcid.org/0000-0002-4330-6240
authors: LM
authors: Zeltser
authors: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center, Beaverton, Oregon 97006, grovek@ohsu.edu.
authors: Kevin L
authors: KL
authors: Grove
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000254:growth & development*; D020738:Leptin / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D054411:Receptors, Leptin / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse
keywords: KATP channels; NPY; arcuate nucleus; development; leptin; mouse