Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice.
A portal venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion that results in hepatic 5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl-5-monophosphate (ZMP) concentrations of approximately 4 micromol/g liver increases hepatic glycogenolysis and glucose output. ZMP is an AMP analog that mimics the regulatory actions of this nucleotide. The aim of this study was to measure hepatic AMP concentrations in response to increasing energy requirements to test the hypothesis that AMP achieves concentrations during exercise, consistent with a role in stimulation of hepatic glucose metabolism. Male C57BL/6J mice (27.4+/- 0.4 g) were subjected to 35 min of rest [sedentary (SED), n=8], underwent short-term (ST, 35 min) moderate (20 m/min, 5% grade) exercise (n=8), or underwent treadmill exercise under similar conditions but until exhaustion (EXH, n=8). Hepatic AMP concentrations were 0.82+/- 0.05, 1.17+/- 0.11, and 2.52+/- 0.16 micromol/g liver in SED, ST, and EXH mice, respectively (P< 0.05). Hepatic energy charge was 0.66+/- 0.01, 0.58+/- 0.02, and 0.33+/- 0.22 in SED, ST, and EXH mice, respectively (P< 0.05). Hepatic glycogen was 11.6+/- 1.0, 8.8+/- 2.2, and 0.0+/- 0.1 mg/g liver in SED, ST, and EXH mice, respectively (P< 0.05). Hepatic AMPK (Thr(172)) phosphorylation was 1.00+/- 0.14, 1.96+/- 0.16, and 7.44+/- 0.63 arbitrary units in SED, ST, and EXH mice, respectively (P< 0.05). Thus exercise increases hepatic AMP concentrations. These data suggest that the liver is highly sensitive to metabolic demands, as evidenced by dramatic changes in cellular energy indicators (AMP) and sensors thereof (AMP-activated protein kinase). In conclusion, AMP is sensitively regulated, consistent with it having an important role in hepatic metabolism.
Camacho
Raul C
RC
Department of Molecular Physiology and Biolphysics and Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, TN, USA. rcamacho@aecom.yu.edu
Donahue
E Patrick
EP
James
Freyja D
FD
Berglund
Eric D
ED
Wasserman
David H
DH
D000091162:AMP-Activated Protein Kinase Kinases; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D005934:Glucagon / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D005082:Physical Exertion / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism
D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005934:Glucagon; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases