Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I

Adam Salmon, Chad Lerner, Yuji Ikeno, Susan M Motch Perrine, Roger McCarter, Christian Sell

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)E545-E553
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume308
Issue number7
DOIs
StatePublished - 2015

Fingerprint

Insulin-Like Growth Factor I
Obesity
High Fat Diet
Fats
Insulin
Rodentia
Phenotype
Gluconeogenesis
Somatomedins
Vascular Resistance
Insulin Resistance
Fatty Acids
Alleles
Diet
Weights and Measures
Glucose

Keywords

  • Gluconeogenesis
  • Insulin
  • Insulin-like growth factor I
  • Metabolism
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I. / Salmon, Adam; Lerner, Chad; Ikeno, Yuji; Perrine, Susan M Motch; McCarter, Roger; Sell, Christian.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 308, No. 7, 2015, p. E545-E553.

Research output: Contribution to journalArticle

Salmon, Adam ; Lerner, Chad ; Ikeno, Yuji ; Perrine, Susan M Motch ; McCarter, Roger ; Sell, Christian. / Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I. In: American Journal of Physiology - Endocrinology and Metabolism. 2015 ; Vol. 308, No. 7. pp. E545-E553.
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