title: Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I.
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.
authors: The Sam and Ann Barshop Institute for Longevity and Aging Studies, Department of Molecular Medicine, and The Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, Audie L. Murphy Veterans Affairs Hospital, San Antonio, Texas; salmona@uthscsa.edu.
authors: Adam B
authors: http://orcid.org/0000-0002-1475-7843
authors: AB
authors: Salmon
authors: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania;
authors: Chad
authors: C
authors: Lerner
authors: The Sam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; The Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, Audie L. Murphy Veterans Affairs Hospital, San Antonio, Texas;
authors: Yuji
authors: Y
authors: Ikeno
authors: Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania; and.
authors: Susan M
authors: SM
authors: Motch Perrine
authors: Center for Developmental and Health Genetics, Pennsylvania State University, University Park, Pennsylvania.
authors: Roger
authors: R
authors: McCarter
authors: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania;
authors: Christian
authors: C
authors: Sell
mesh_terms: D000818:Animals; D001823:Body Composition / Q000235:genetics; D059305:Diet, High-Fat; D060467:Disease Resistance / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D007333:Insulin Resistance / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics* / Q000378:metabolism
chemical_list: D007334:Insulin-Like Growth Factor I
keywords: gluconeogenesis; insulin; insulin-like growth factor I; metabolism; obesity
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