Adrenergic regulation of HSL serine phosphorylation and activity in human skeletal muscle during the onset of exercise

Skeletal muscle hormone-sensitive lipase (HSL) activity is increased by contractions and increases in blood epinephrine (EPI) concentrations and cyclic AMP activation of the adrenergic pathway during prolonged exercise. To determine the importance of hormonal stimulation of HSL activity during the onset of moderate- and high-intensity exercise, nine men [age 24.3 ± 1.2 yr, 80.8 ± 5.0 kg, peak oxygen consumption (V̇o2 peak) 43.9 ± 3.6 ml·kg−1·min−1] cycled for 1 min at ∼65% V̇o2 peak, rested for 60 min, and cycled at ∼90% V̇o2 peak for 1 min. Skeletal muscle biopsies were taken pre- and postexercise, and arterial blood was sampled throughout exercise. Arterial EPI increased ( P < 0.05) postexercise at 65% (0.45 ± 0.10 to 0.78 ± 0.27 nM) and 90% V̇o2 peak (0.57 ± 0.34 to 1.09 ± 0.50 nM). HSL activity increased ( P < 0.05) following 1 min of exercise at 65% V̇o2 peak [1.05 ± 0.39 to 1.78 ± 0.54 mmol·min−1·kg dry muscle (dm)−1] and 90% V̇o2 peak (1.07 ± 0.24 to 1.91 ± 0.62 mmol·min−1·kg dm−1). Cyclic AMP content also increased ( P < 0.05) at both exercise intensities (65%: 1.52 ± 0.67 to 2.75 ± 1.12, 90%: 1.85 ± 0.65 to 2.64 ± 0.93 μmol/kg dm). HSL Ser660 phosphorylation (∼55% increase) and ERK1/2 phosphorylation (∼33% increase) were augmented following exercise at both intensities, whereas HSL Ser563 and Ser565 phosphorylation were not different from rest. The results indicate that increases in arterial EPI concentration during the onset of moderate- and high-intensity exercise increase cyclic AMP content, which results in the phosphorylation of HSL Ser660. This adrenergic stimulation contributes to the increase in HSL activity that occurs in human skeletal muscle in the first minute of exercise at 65% and 90% V̇o2 peak.