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Journal article
Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I
American journal of physiology: endocrinology and metabolism, v 308(7), pp E545-E553
01 Apr 2015
PMID: 25648834
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The extension of lifespan due to reduced insulin-like growth factor 1 (IGF-I) signaling in mice has been proposed to be mediated through alterations in metabolism. Previously, we showed that mice homozygous for an insertion in the Igf1 allele have reduced levels of IGF-I, are smaller, and have an extension of maximum lifespan. Here, we tested whether this specific reduction of IGF-I alters glucose metabolism both on normal rodent chow and in response to high-fat feeding. We found that female IGF-I-deficient mice were lean on a standard rodent diet but paradoxically displayed an insulin-resistant phenotype. However, these mice gained significantly less weight than normal controls when placed on a high-fat diet. In control animals, insulin response was significantly impaired by high-fat feeding, whereas IGF-I-deficient mice showed a much smaller shift in insulin response after high-fat feeding. Gluconeogenesis was also elevated in the IGF-I-deficient mice relative to controls on both normal and high-fat diet. An analysis of metabolism and respiratory quotient over 24 h indicated that the IGF-I-deficient mice preferentially utilized fatty acids as an energy source when placed on a high-fat diet. These results indicate that reduction in the circulating and tissue IGF-I levels can produce a metabolic phenotype in female mice that increases peripheral insulin resistance but renders animals resistant to the deleterious effects of high-fat feeding.
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Details
- Title
- Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I
- Creators
- Adam B Salmon - Murphy Oil CorporationChad Lerner - Drexel UniversityYuji Ikeno - The University of Texas Health Science Center at San AntonioSusan M Motch PerrineRoger McCarter - Pennsylvania State UniversityChristian Sell - Drexel University
- Publication Details
- American journal of physiology: endocrinology and metabolism, v 308(7), pp E545-E553
- Publisher
- American Physiological Society (APS)
- Grant note
- AG-223343 / NIA NIH HHS AG-02243 / NIA NIH HHS T32-AG021890-05 / NIA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000352194300001
- Scopus ID
- 2-s2.0-84926373468
- Other Identifier
- 991019169629604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Physiology