Neuron-specific Deletion of a Single Copy of the Insulin-like Growth Factor-1 Receptor Gene Reduces Fat Accumulation during Aging

S. Freude; K. Schilbach; M. M. Hettich; H. S. Brönneke; J. Zemva; W. Krone; M. Schubert

doi:10.1055/s-0031-1298018

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2012; 44(02): 99-104
DOI: 10.1055/s-0031-1298018

Original Basic

Neuron-specific Deletion of a Single Copy of the Insulin-like Growth Factor-1 Receptor Gene Reduces Fat Accumulation during Aging

S. Freude

¹Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

³Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

,

K. Schilbach

¹Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany

,

M. M. Hettich

¹Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany

⁴Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

,

H. S. Brönneke

³Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

,

J. Zemva

¹Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

³Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

,

W. Krone

¹Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

³Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

,

M. Schubert

¹Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany

²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

³Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

› Institutsangaben

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.

Key words

IGF-1 - adipose tissue - energy homeostasis - leptin - neurons

Volltext

Referenzen

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