TY - JOUR
T1 - Down-regulation of AMP-activated protein kinase by calorie restriction in rat liver
AU - To, Kazuo
AU - Yamaza, Haruyoshi
AU - Komatsu, Toshimitsu
AU - Hayashida, Takahiro
AU - Hayashi, Hiroko
AU - Toyama, Hiroaki
AU - Chiba, Takuya
AU - Higami, Yoshikazu
AU - Shimokawa, Isao
N1 - Funding Information:
The authors wish to thank Yutaka Araki and the staff at the Biomedical Research Center, Center of Frontier Life Sciences at Nagasaki University, for their technical assistance and animal care. This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (No. 15390128).
PY - 2007/11
Y1 - 2007/11
N2 - AMP-activated protein kinase (AMPK) may act as a key enzyme for metabolic adaptation to calorie restriction (CR) or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling, an experimental intervention for lifespan extension in animals. We investigated the protein levels of AMPKα and a downstream enzyme, acetyl-CoA carboxylase (ACC), by immunoblotting of liver and quadriceps femoris muscle (QFM) extracts from 6-month-old wild-type (W) and GH-suppressed transgenic (Tg) Wistar rats fed ad libitum (AL) or 30% CR diets from 6 weeks of age. A modified alternate-day feeding regimen for CR yielded a fed-fasted cycle in CR rats, and therefore the effects of overnight fasting in W-AL rats were also evaluated. CR decreased threonine-172-phosphorylated AMPKα (p-AMPKα; an activated form) levels in the liver, whereas the CR-fed-fasted cycle or overnight fasting did not significantly affect the p-AMPKα level. In the QFM, the p-AMPKα level was slightly elevated in the CR-fasted phase, but greatly increased in the AL-fasted phase. Suppression of GH did not affect the p-AMPKα level. The phosphorylated-ACC levels did not alter in parallel with the p-AMPKα level, particularly in the liver. The present results suggest that CR down-regulates the AMPK activity in the liver on a long-term basis.
AB - AMP-activated protein kinase (AMPK) may act as a key enzyme for metabolic adaptation to calorie restriction (CR) or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling, an experimental intervention for lifespan extension in animals. We investigated the protein levels of AMPKα and a downstream enzyme, acetyl-CoA carboxylase (ACC), by immunoblotting of liver and quadriceps femoris muscle (QFM) extracts from 6-month-old wild-type (W) and GH-suppressed transgenic (Tg) Wistar rats fed ad libitum (AL) or 30% CR diets from 6 weeks of age. A modified alternate-day feeding regimen for CR yielded a fed-fasted cycle in CR rats, and therefore the effects of overnight fasting in W-AL rats were also evaluated. CR decreased threonine-172-phosphorylated AMPKα (p-AMPKα; an activated form) levels in the liver, whereas the CR-fed-fasted cycle or overnight fasting did not significantly affect the p-AMPKα level. In the QFM, the p-AMPKα level was slightly elevated in the CR-fasted phase, but greatly increased in the AL-fasted phase. Suppression of GH did not affect the p-AMPKα level. The phosphorylated-ACC levels did not alter in parallel with the p-AMPKα level, particularly in the liver. The present results suggest that CR down-regulates the AMPK activity in the liver on a long-term basis.
KW - AMP-activated protein kinase
KW - Acetyl-CoA carboxylase
KW - Aging
KW - Calorie restriction
KW - Growth hormone
KW - IGF-1
KW - Metabolic adaptation
UR - http://www.scopus.com/inward/record.url?scp=35448976050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35448976050&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2007.07.003
DO - 10.1016/j.exger.2007.07.003
M3 - Article
C2 - 17709221
AN - SCOPUS:35448976050
SN - 0531-5565
VL - 42
SP - 1063
EP - 1071
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 11
ER -