title: Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility.
abstract: Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Lepr(flox/flox) IR(flox/flox) mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Lepr(flox/flox) IR(flox/flox) female mice display elevated serum testosterone levels and ovarian abnormalities, resulting in reduced fertility. We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function.
authors.affiliation: Center for Diabetes and Endocrine Research, Department of Physiology and Pharmacology, College of Medicine, The University of Toledo, Toledo, OH 43614, USA.
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Hill
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuda
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Williams
authors.forename: Eric D
authors.initials: ED
authors.lastname: Berglund
authors.forename: William L
authors.initials: WL
authors.lastname: Holland
authors.forename: You-Ree
authors.initials: YR
authors.lastname: Cho
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Chuang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Michelle
authors.initials: M
authors.lastname: Choi
authors.forename: Danielle
authors.initials: D
authors.lastname: Lauzon
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppari
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zigman
authors.forename: Streamson
authors.initials: S
authors.lastname: Chua
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D013739:Testosterone; D011333:Pro-Opiomelanocortin