Down-regulation of AMP-activated protein kinase by calorie restriction in rat liver.
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 AMPKalpha 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 6weeks 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 AMPKalpha (p-AMPKalpha; an activated form) levels in the liver, whereas the CR-fed-fasted cycle or overnight fasting did not significantly affect the p-AMPKalpha level. In the QFM, the p-AMPKalpha 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-AMPKalpha level. The phosphorylated-ACC levels did not alter in parallel with the p-AMPKalpha level, particularly in the liver. The present results suggest that CR down-regulates the AMPK activity in the liver on a long-term basis.
To
Kazuo
K
Department of Investigative Pathology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 12-4 Sakamoto 1-chome, Nagasaki City 852-8523, Japan.
Yamaza
Haruyoshi
H
Komatsu
Toshimitsu
T
Hayashida
Takahiro
T
Hayashi
Hiroko
H
Toyama
Hiroaki
H
Chiba
Takuya
T
Higami
Yoshikazu
Y
Shimokawa
Isao
I
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D015536:Down-Regulation; D013006:Growth Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008136:Longevity; D008297:Male; D009097:Multienzyme Complexes / Q000032:analysis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D030781:Organisms, Genetically Modified; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009097:Multienzyme Complexes; D013006:Growth Hormone; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase