Effects of aging and life-long moderate calorie restriction on IL-15 signaling in the rat white adipose tissue

Silvia Giovannini, C. S. Carter, C. Leeuwenburgh, Andrea Flex, Federico Biscetti, D. Morgan, A. Laudisio, Daniele Coraci, Giulio Maccauro, Giuseppe Zuccala', Pietro Caliandro, Roberto Bernabei, Emanuele Marzetti

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OBJECTIVE: Phosphorylation of insulin receptor substrate (IRS) 1 by tumor necrosis factor alpha (TNF-α) has been implicated as a factor contributing to insulin resistance. Administration of IL-15 reduces adipose tissue deposition in young rats and stimulates secretion of adiponectin, an insulin sensitizing hormone that inhibits the production and activity of TNF-a. We aimed at investigating the effects of age life-long moderate calorie restriction (CR) on IL-15 and TNF-α signaling in rat white adipose tissue (WAT). MATERIALS AND METHODS: Thirty-six 8-month-old, 18-month-old, and 29-month-old male Fischer344 Brown Norway F1 rats (6 per group) were either fed ad libitum (AL) or calorie restricted by 40%. The serum levels of IL-15 and IL-15 receptor a-chain (IL-15Ra) were increased by CR controls regardless of age. An opposite pattern was detected in WAT. In addition, CR reduced gene expression of TNF-a and cytosolic IRS1 serine phosphorylation in WAT, independently from age. RESULTS: IL-15 signaling in WAT is increased over the course of aging in AL rats compared with CR rodents. Protein levels of IL-15Ra are greater in WAT of AL than in CR rats independently from age. This adaptation was paralleled by increased IRS1 phosphorylation through TNF-a-mediated insulin resistance. Adiponectin decreased at old age in AL rats, while no changes were evident in CR rats across age groups. CONCLUSIONS: IL-15 signaling could therefore represent a potential target for interventions to counteract metabolic alterations and the deterioration of body composition during aging.
Original languageEnglish
Pages (from-to)2738-2749
Number of pages12
JournalEuropean Review for Medical and Pharmacological Sciences
Publication statusPublished - 2020


  • Adipose tissue
  • Aging
  • Calorie restriction
  • IL-15
  • IL-15 receptor
  • IRS1
  • NF-κB
  • TNF-α


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