title: Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.
abstract: Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kocalis
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Hagan
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Leena
authors.initials: L
authors.lastname: George
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Maxine K
authors.initials: MK
authors.lastname: Turney
authors.affiliation: Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, United States ; Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Siuta
authors.affiliation: Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, United States.
authors.forename: Gloria N
authors.initials: GN
authors.lastname: Laryea
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Lindsey C
authors.initials: LC
authors.lastname: Morris
authors.affiliation: Center for Prevention of Preterm Birth, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Muglia
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Printz
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Gregg D
authors.initials: GD
authors.lastname: Stanwood
authors.affiliation: Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, United States ; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States ; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Niswender
keywords: AgRP neurons; CNS insulin; Energy balance; Food intake; Obesity; POMC neurons; Rictor; mTORC2