The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice

Mark W Hamrick, A. Dukes, P. Arounleut, Colleen M. Davis, Sudharsan Periyasamy Thandavan, S. Mork, S. Herberg, Maribeth H Johnson, Carlos M Isales, William D Hill, L. Otvos, Eric Jacques Belin de Chantemele

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Muscle- and liver-derived IGF-1 play important roles in muscle anabolism throughout growth and aging. Yet, prolonged food restriction is thought to increase longevity in part by lowering levels of IGF-1, which in turn reduces the risk for developing various cancers. The dietary factors that modulate IGF-1 levels are, however, poorly understood. We tested the hypothesis that the adipokine leptin, which is elevated with food intake and suppressed during fasting, is a key mediator of IGF-1 levels with aging and food restriction. First, leptin levels in peripheral tissues were measured in young mice fed ad libitum, aged mice fed ad libitum, and aged calorie-restricted (CR) mice. A group of aged CR mice were also treated with recombinant leptin for 10. days. Later, aged mice fed ad libitum were treated with saline (VEH) or with a novel leptin receptor antagonist peptide (Allo-aca) and tissue-specific levels of IGF-1 were determined. On one hand, recombinant leptin induced a three-fold increase in liver-derived IGF-1 and a two-fold increase in muscle-derived IGF-1 in aged, CR mice. Leptin also significantly increased serum growth hormone levels in the aged, CR mice. On the other, the leptin receptor antagonist Allo-aca did not alter body weight or muscle mass in treated mice compared to VEH mice. Allo-aca did, however, produce a significant (20%) decline in liver-derived IGF-1 as well as an even more pronounced (>. 50%) decrease in muscle-derived IGF-1 compared to VEH-treated mice. The reduced IGF-1 levels in Allo-aca treated mice were not accompanied by any significant change in growth hormone levels compared to VEH mice. These findings suggest that leptin receptor antagonists may represent novel therapeutic agents for attenuating IGF-1 signaling associated with aging, and could potentially mimic some of the positive effects of calorie restriction on longevity.

Original languageEnglish (US)
Pages (from-to)92-96
Number of pages5
JournalExperimental Gerontology
Volume70
DOIs
StatePublished - Oct 1 2015

Fingerprint

Adipokines
Leptin
Insulin-Like Growth Factor I
Liver
Muscle
Muscles
Leptin Receptors
Aging of materials
Growth Hormone
Tissue
Food
Fasting
Eating
Body Weight

Keywords

  • Aging
  • Calorie restriction
  • Food intake
  • Longevity

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice. / Hamrick, Mark W; Dukes, A.; Arounleut, P.; Davis, Colleen M.; Periyasamy Thandavan, Sudharsan; Mork, S.; Herberg, S.; Johnson, Maribeth H; Isales, Carlos M; Hill, William D; Otvos, L.; Belin de Chantemele, Eric Jacques.

In: Experimental Gerontology, Vol. 70, 01.10.2015, p. 92-96.

Research output: Contribution to journalArticle

Hamrick, Mark W ; Dukes, A. ; Arounleut, P. ; Davis, Colleen M. ; Periyasamy Thandavan, Sudharsan ; Mork, S. ; Herberg, S. ; Johnson, Maribeth H ; Isales, Carlos M ; Hill, William D ; Otvos, L. ; Belin de Chantemele, Eric Jacques. / The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice. In: Experimental Gerontology. 2015 ; Vol. 70. pp. 92-96.
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