Similar metabolic responses to calorie restriction in lean and obese Zucker rats.
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.
Chiba
Takuya
T
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. takuya@nagasaki-u.ac.jp
Komatsu
Toshimitsu
T
Nakayama
Masahiko
M
Adachi
Toshiyuki
T
Tamashiro
Yukari
Y
Hayashi
Hiroko
H
Yamaza
Haruyoshi
H
Higami
Yoshikazu
Y
Shimokawa
Isao
I
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001835:Body Weight; D031204:Caloric Restriction; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000097:blood; D005943:Gluconeogenesis / Q000235:genetics; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010902:Pituitary Gland / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000172:deficiency / Q000378:metabolism; D013851:Thinness / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D054439:Ghrelin; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D054411:Receptors, Leptin; D014157:Transcription Factors; D013006:Growth Hormone