Similar metabolic responses to calorie restriction in lean and obese Zucker rats

Takuya Chiba*, Toshimitsu Komatsu, Masahiko Nakayama, Toshiyuki Adachi, Yukari Tamashiro, Hiroko Hayashi, Haruyoshi Yamaza, Yoshikazu Higami, Isao Shimokawa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalMolecular and Cellular Endocrinology
Issue number1-2
Publication statusPublished - 2009 Oct 15
Externally publishedYes


  • Glucose and lipid metabolism
  • Hypothalamus
  • Neuroendocrine
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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