The effects of graded levels of calorie restriction: II. Impact of short term calorie and protein restriction on circulating hormone levels, glucose homeostasis and oxidative stress in male C57BL/6 mice

Sharon E. Mitchell, Camille Delville, Penelope Konstantopedos, Jane Hurst, Davina Derous, Cara Leanne Green, Luonan Chen, Jackie J.D. Han, Yingchun Wang, Daniel E. L. Promislow, David Lusseau, Alex Douglas, John R. Speakman

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Limiting food intake attenuates many of the deleterious effects of aging, impacting upon healthspan and leading to an increased lifespan. Whether it is the overall restriction of calories (calorie restriction: CR) or the incidental reduction in macronutrients such as protein (protein restriction: PR) that mediate these effects is unclear. The impact of 3 month CR or PR, (10 to 40%), on C57BL/6 mice was compared to controls fed ad libitum. Reductions in circulating leptin, tumor necrosis factor-α and insulin-like growth factor-1 (IGF-1) were relative to the level of CR and individually associated with morphological changes but remained unchanged following PR. Glucose tolerance and insulin sensitivity were improved following CR but not affected by PR. There was no indication that CR had an effect on oxidative damage, however CR lowered antioxidant activity. No biomarkers of oxidative stress were altered by PR. CR significantly reduced levels of major urinary proteins suggesting lowered investment in reproduction. Results here support the idea that reduced adipokine levels, improved insulin/IGF-1 signaling and reduced reproductive investment play important roles in the beneficial effects of CR while, in the short-term, attenuation of oxidative damage is not applicable. None of the positive effects were replicated with PR.
Original languageEnglish
Pages (from-to)23213-23237
Number of pages25
Issue number27
Early online date1 Jun 2015
Publication statusPublished - 1 Jun 2015



  • calorie restriction
  • protein restriction
  • glucose homoeostasis
  • oxidative stress
  • adipokines

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