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Horm Metab Res 2012; 44(02): 99-104
DOI: 10.1055/s-0031-1298018
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

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

S. Freude
1   Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
3   Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
,
K. Schilbach
1   Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany
,
M. M. Hettich
1   Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany
4   Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
,
H. S. Brönneke
3   Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
,
J. Zemva
1   Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
3   Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
,
W. Krone
1   Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
3   Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
,
M. Schubert
1   Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
3   Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
› Author Affiliations
Further Information

Publication History

received 29 July 2011

accepted 30 November 2011

Publication Date:
23 December 2011 (online)

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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
 

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