Calorie restriction initiated at a young age activates the Akt/PKCζ/λ-Glut4 pathway in rat white adipose tissue in an insulin-independent manner

Seongjoon Park, Toshimitsu Komatsu, Hiroko Hayashi, Haruyoshi Yamaza, Takuya Chiba, Yoshikazu Higami, Kazunao Kuramoto, Isao Shimokawa

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10 Citations (Scopus)


Calorie restriction (CR) may exert an anti-aging effect through a metabolic adaptation to limited energy intake. The present study investigated the effect of CR on insulin signaling in response to glucose load in the epididymal adipose tissue of male F344 rats at 7 and 22 months of age. Young and middle-aged rats were fed ad libitum (AL) or 30% CR diets for 4 months, underwent glucose tolerance tests and were sacrificed 15 min after an intraperitoneal glucose or saline injection to evaluate glucose-stimulated insulin response and subsequent activation of insulin signaling molecules in the adipose tissue. In the 7- and 22- month AL groups, glucose administration increased serum insulin levels and also increased phosphorylated (p) levels of the insulin receptor (IR), v-akt murine thymoma viral oncogene homolog (Akt), protein kinase C (PKC) ζ/λ and the membrane fraction of glucose transporter 4 (mGlut4). In contrast, in the 7-month CR group, p-Akt, p-PKCζ/λ and mGlut4 levels were upregulated without glucose stimulation; the glucose load augmented the p-IR level but there was no additional activation of the downstream molecules. In the 22-month CR group, these unexpected findings were not observed. In summary, basal levels of insulin signaling molecules such as p-Akt, p-PKCζ/λ, and mGlut4 were significantly increased with a low insulin response in the 7-month CR group. The present results suggest the presence of an age-specific insulin-independent mechanism that is induced by CR to regulate energy metabolism in white adipose tissue.

Original languageEnglish
Pages (from-to)293-302
Number of pages10
Issue number4
Publication statusPublished - 2008 Dec
Externally publishedYes



  • Adipose tissue
  • Aging
  • Calorie restriction
  • Glucose intolerance
  • Insulin signal

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

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