title: Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis.
abstract: Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.
authors.affiliation: Department of Mouse Genetics and Metabolism, Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Center of Molecular Medicine, University of Cologne,Cologne, Germany.
authors.forename: A Christine
authors.initials: AC
authors.lastname: Könner
authors.forename: Simon
authors.initials: S
authors.lastname: Hess
authors.forename: Sulay
authors.initials: S
authors.lastname: Tovar
authors.forename: Andrea
authors.initials: A
authors.lastname: Mesaros
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Lasheras
authors.forename: Nadine
authors.initials: N
authors.lastname: Evers
authors.forename: Linda A W
authors.initials: LA
authors.lastname: Verhagen
authors.forename: Hella S
authors.initials: HS
authors.lastname: Brönneke
authors.forename: André
authors.initials: A
authors.lastname: Kleinridders
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hampel
authors.forename: Peter
authors.initials: P
authors.lastname: Kloppenburg
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
mesh_terms: D000200:Action Potentials; D050154:Adiposity; D000818:Animals; D002153:Calorimetry, Indirect; D002395:Catecholamines / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression; D006706:Homeostasis / Q000187:drug effects*; D006946:Hyperinsulinism / Q000235:genetics; D007328:Insulin / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D002395:Catecholamines; D007328:Insulin; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D011972:Receptor, Insulin; D003042:Cocaine