α₂-AMPK activity is not essential for an increase in fatty acid oxidation during low-intensity exercise

Abstract

A single bout of exercise increases glucose uptake and fatty acid oxidation in skeletal muscle, with a corresponding activation of AMP-activated protein kinase (AMPK). While the exercise-induced increase in glucose uptake is partly due to activation of AMPK, it is unclear whether the increase of fatty acid oxidation is dependent on activation of AMPK. To examine this, transgenic mice were produced expressing a dominant-negative (DN) mutant of alpha(1)-AMPK (alpha(1)-AMPK-DN) in skeletal muscle and subjected to treadmill running. alpha(1)-AMPK-DN mice exhibited a 50% reduction in alpha(1)-AMPK activity and almost complete loss of alpha(2)-AMPK activity in skeletal muscle compared with wild-type littermates (WT). The fasting-induced decrease in respiratory quotient (RQ) ratio and reduced body weight were similar in both groups. In contrast with WT mice, alpha(1)-AMPK-DN mice could not perform high-intensity (30 m/min) treadmill exercise, although their response to low-intensity (10 m/min) treadmill exercise was not compromised. Changes in oxygen consumption and the RQ ratio during sedentary and low-intensity exercise were not different between alpha(1)-AMPK-DN and WT. Importantly, at low-intensity exercise, increased fatty acid oxidation in response to exercise in soleus (type I, slow twitch muscle) or extensor digitorum longus muscle (type II, fast twitch muscle) was not impaired in alpha(1)-AMPK-DN mice, indicating that alpha(1)-AMPK-DN mice utilize fatty acid in the same manner as WT mice during low-intensity exercise. These findings suggest that an increased alpha(2)-AMPK activity is not essential for increased skeletal muscle fatty acid oxidation during endurance exercise.

Effect of exercise intensity and AICAR on isoform-specific expressions of murine skeletal muscle PGC-1α mRNA: a role of β2-adrenergic receptor activation

“…Because ␣1-AMPK-DN mice cannot maintain a 30 m/min running speed for 30 min (24), the intensity of exercise was set at 20 m/min for 30 min. ␣2-AMPK activity was severely inhibited in the skeletal muscle of the ␣1-AMPK-DN mice when sedentary and after running at 10 m/min (24). ␣2-AMPK activity was also inhibited in the skeletal muscle of the ␣1-AMPK-DN mice just after running at 20 m/min for 30min (Fig.…”

“…Transgenic mice were produced expressing a dominant-negative (DN) mutant of ␣1-AMPK in skeletal muscle (␣1-AMPK-DN mice) as previously described (24). Briefly, human skeletal muscle ␣-actin promoter provided by Drs.…”

“…E. D. Hardeman and K. Guven (Children's Medical Research Institute, Westmead, Australia) was used to express ␣1-AMPK-DN in skeletal muscle. ␣1-AMPK-DN mice exhibited a 50% reduction in ␣1-AMPK activity and almost complete loss of ␣2-AMPK activity in skeletal muscle compared with wild-type littermates (24). Male chimeras (BDF1 background) harboring the ␣1-AMPK-DN transgene were mated with pure C57BL/6J females to obtain F 1 offspring.…”

AMPKα2deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle

“…However, studies utilizing transgenic mouse models where AMPK is either inactive or knocked out reveal conflicting results (24 -26, 30). Some studies suggest that AMPK is necessary in the regulation of glucose and FA metabolism (24,25), whereas other studies show that AMPK is not necessary to measure increases in substrate metabolism during exercise or other metabolic challenges (26,30).Therefore, the purpose of this study was to determine 1) whether a caffeine-induced increase in intracellular [Ca 2ϩ ] regulates muscle glucose uptake, FA uptake, and FA oxidation solely via AMPK␣ 2 activation and 2) whether the ␣ 2 -subunit of AMPK is essential to increase glucose uptake, FA uptake, and FA oxidation in contracting skeletal muscle in a hindlimb perfusion system. Although the perfusion system is not as physiologically relevant as tracer studies in live animals, it allowed us to measure glucose uptake, FA uptake, and FA oxidation at various time points and provided an in situ model.…”

Nifedipine increases energy expenditure by increasing PGC-1α expression in skeletal muscle

“…Mice then exercised on a treadmill at a speed of 10 m min À1 , and VO 2 , VCO 2 and RER were measured for 30 min as previously described. 20 Quantitative real-time PCR Total RNA was isolated using TRIzol reagent (Invitrogen Japan KK, Tokyo, Japan). DNase-treated RNA was reverse transcribed using a PrimeScript RT reagent Kit (Takara Bio, Shiga, Japan).…”