title: Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons.
abstract: OBJECTIVE
  The ventromedial hypothalamic nucleus (VMH) regulates energy balance and glucose homeostasis. Leptin and insulin exert metabolic effects via their cognate receptors expressed by the steroidogenic factor 1 (SF1) neurons within the VMH. However, detailed cellular mechanisms involved in the regulation of these neurons by leptin and insulin remain to be identified.
  
  
  METHODS
  We utilized genetically-modified mouse models and performed patch-clamp electrophysiology experiments to resolve this issue.
  
  
  RESULTS
  We identified distinct populations of leptin-activated and leptin-inhibited SF1 neurons. In contrast, insulin uniformly inhibited SF1 neurons. Notably, we found that leptin-activated, leptin-inhibited, and insulin-inhibited SF1 neurons are distinct subpopulations within the VMH. Leptin depolarization of SF1 neuron also required the PI3K p110β catalytic subunit. This effect was mediated by the putative transient receptor potential C (TRPC) channel. On the other hand, hyperpolarizing responses of SF1 neurons by leptin and insulin required either of the p110α or p110β catalytic subunits, and were mediated by the putative ATP-sensitive K(+) (KATP) channel.
  
  
  CONCLUSIONS
  Our results demonstrate that specific PI3K catalytic subunits are responsible for the acute effects of leptin and insulin on VMH SF1 neurons, and provide insights into the cellular mechanisms of leptin and insulin action on VMH SF1 neurons that regulate energy balance and glucose homeostasis.
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea. Electronic address: jwsohn@kaist.ac.kr.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Sohn
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Pharmacology, Yonsei University Wonju College of Medicine, Wonju, 26426, South Korea.
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Syann
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address: Kevin.Williams@UTSouthwestern.edu.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Williams
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
keywords: Cellular mechanism; Conditional knockout mouse; Functional heterogeneity; Homeostasis; Patch clamp technique