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Am J Physiol Endocrinol Metab 287: E1032-E1037, 2004. First published July 13, 2004; doi:10.1152/ajpendo.00172.2004
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TRANSLATIONAL PHYSIOLOGY

Metabolic adaptations to fasting and chronic caloric restriction in heart, muscle, and liver do not include changes in AMPK activity

Asensio A. Gonzalez,1 Reetu Kumar,1 Jacob D. Mulligan,1 Ashley J. Davis,1 Richard Weindruch,1 and Kurt W. Saupe1,2

Departments of 1Medicine and 2Physiology, University of Wisconsin, Madison, Wisconsin 53706

Submitted 16 April 2004 ; accepted in final form 2 July 2004

Activation of adenosine monophosphate-activated protein kinase (AMPK) plays a central role in allowing cells to adapt to nutrient deprivation in vitro. This link between AMPK activity and nutritional status has raised the possibility that AMPK plays a role in the metabolic adaptation to acute and chronic nutritional stress. However, the effects of nutritional stress on AMPK activity in vivo have not been systematically evaluated. To address this, we measured the effects of 24 h of fasting and 4 mo of caloric restriction (CR) on AMPK{alpha}1 and -{alpha}2 activities in heart, skeletal muscle, and liver in mice. Although fasting caused the expected changes in body weight, plasma leptin, and free fatty acids, it did not increase AMPK activity in heart or skeletal muscle and only increased liver AMPK activity by ~20% (P = 0.10). Likewise, CR caused the expected changes in body weight, plasma leptin, and free fatty acids but did not alter AMPK activity in any of the three tissues. Although CR did not alter liver AMPK activity, it dramatically decreased the amount of phosphorylated acetyl-CoA carboxylase, and this was found to be due to decreased protein expression. Plasma leptin, a putative activator of AMPK, varied eightfold across the four groups of mice in the absence of changes in AMPK activity in any tissue. We conclude that, although the metabolic adaptations to fasting and CR include changes in plasma leptin concentration and phosphorylated acetyl-CoA carboxylase, these effects occur without changes in AMPK activity.

adenosine monophosphate-activated protein kinase; leptin; acetyl-coenzyme A carboxylase


Address for reprint requests and other correspondence: K. W. Saupe, 1630 Medical Sciences Center, 1300 Univ. Ave., Madison, WI 53706 (E-mail: kws{at}medicine.wisc.edu)




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