Adenosine 5'-Monophosphate (AMP) Activated Protein Kinase (AMPK) Activation in Liver Is Sensitively Regulated by Exercise in C57BL/6J Mice
Abstract Number: 58-OR
Authors: RAUL C. CAMACHO, E. PATRICK DONAHUE, FREYJA D. JAMES, DAVID H. WASSERMAN
Institutions: Nashville, TN
Results: The putative energy sensor, AMPK, is sensitive to glycogen stores in muscle during exercise. The role of AMPK in liver, another tissue important to sustaining energy homeostasis, remains to be clearly defined. The hypothesis was that AMPK phosphorylation is dependent on energy state and would correspond to hepatic glycogen levels. To test this, male mice (27.4±0.4 g) were maintained at rest (SED, n=8), or exercised (20 m•min-1, 5% grade) for 35 min (NEX, n=8) or until exhaustion (EXH, n=8; time to exhaustion was 84±12 min). Data from liver are shown below.
∗Different than SED, p<0.05; †Different than SED and MOD, p<0.05Exercise increased hepatic AMPK phosphorylation, the magnitude of which corresponded to the energy demands of exercise, as reflected in the extent of hepatic glycogen depletion and AMP accumulation. Changes in hepatic glycogen were not accompanied by detectable changes in glycogen phosphorylase or synthase activity ratios, suggesting that in vivo microenvironment (e.g. allosteric regulation by AMP) is responsible for increased phosphorylase activity. Exercise for 35 min resulted in ∼40% and ∼200% increases in hepatic AMP and AMPK phosphorylation. Exhaustive exercise resulted in ∼300% and ∼750% increases in hepatic AMP and AMPK phosphorylation. This suggests that the liver is highly sensitive to metabolic demands as evidenced by dramatic increases in cellular energy indicators (AMP) and sensors thereof (AMPK). In conclusion, AMPK is sensitively regulated and may be an important metabolic controller in the liver, as has been proposed in muscle.
|Hepatic Glycogen (mg/g tissue)||22.6±0.5||16.1±3.1∗||1.2±0.6†|
|Hepatic AMP (μmol/g tissue)||0.82±0.05||1.17±0.11∗||2.52±0.16†|
|AMPK (Thr172) Phosphorylation (Arbitrary Units)||1.00±0.14||1.96±0.16∗||7.44±0.63†|
|Glycogen Phosphorylase Activity Ratio||0.90±0.03||0.82±0.04||0.81±0.4|
|Glycogen Synthase Activity Ratio||0.48±0.02||0.52±0.03||0.54±0.04|