title: Neuron-specific deletion of a single copy of the insulin-like growth factor-1 receptor gene reduces fat accumulation during aging.
abstract: Insulin, insulin-like growth factor-1 (IGF-1), and leptin signaling have been proposed to play an important role in regulating energy homeostasis. In order to specifically address the role of neuronal IGF-1 receptor (IGF-1R) signaling for energy expenditure and metabolism we used conditional mutagenesis. Deletion of one copy of the IGF-1R specifically in post-mitotic neurons (nIGF-1R(+/-) ) does not result in growth retardation or skeletal abnormalities. Interestingly, male nIGF-1R(+/-)  mice accumulate less fat mass during aging accompanied with decreased leptin levels compared to wild-type littermates. Furthermore, male nIGF-1R(+/-)  mice present with increased locomotor activity and energy expenditure. In contrast, female nIGF-1R(+/-)  mice remained nearly unaffected. Circadian pattern of locomotor activity and energy expenditure as well as food and water intake did not change. Consistent with increased locomotor activity, the respiratory quotient was shifted to increased fat oxidation in nIGF-1R(+/-)  mice. Surprisingly, serum IGF-1 and IGF-1 binding protein 3 (IGF-BP3) concentrations were decreased in nIGF-1R(+/-)  mice despite the presence of normal pituitaries suggesting a functional feedback mechanism via neuronal IGF-1Rs, which regulate serum IGF-1 levels. Thus, we show that neuron-specific IGF-1R deletion in male mice decreases body fat accumulation and increases energy expenditure during aging.
authors.affiliation: Center for Endocrinology, Diabetes, and Preventive Medicine, University of Cologne, Cologne, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Freude
authors.forename: K
authors.initials: K
authors.lastname: Schilbach
authors.forename: M M
authors.initials: MM
authors.lastname: Hettich
authors.forename: H S
authors.initials: HS
authors.lastname: Brönneke
authors.forename: J
authors.initials: J
authors.lastname: Zemva
authors.forename: W
authors.initials: W
authors.lastname: Krone
authors.forename: M
authors.initials: M
authors.lastname: Schubert
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000375:Aging / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D004734:Energy Metabolism; D007328:Insulin / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017526:Receptor, IGF Type 1