Chronic AICAR treatment, but not voluntary exercise training, increases nicotinamide phosphoribosyl transferase (Nampt) protein expression in an AMPK‐dependent manner in mouse quadriceps muscle

Abstract

Nampt regulates intracellular NAD+ levels and may modulate sirtuin activity. AMP-activated protein kinase (AMPK) may regulate Nampt expression in skeletal muscle. We investigated whether chronic endurance exercise or treatment with aminoimidazole carboxamide ribonucleotide (AICAR) alter skeletal muscle Nampt concentrations in an AMPK-dependent fashion. Whole-body AMPK α2 (catalytic subunit) KO mice and WT littermates (n=9–11) were injected subcutaneously with AICAR or saline for 28 d (500 mg/kg body weight). Separately, WT and α2 KO animals (n=10–16) performed voluntary wheel-cage exercise for 28 d or served as sedentary controls. Animals were sacrificed 24 h after the last AICAR injection or 14–16 h after the last exercise bout. Nampt protein expression in quadriceps muscle was assessed via immunoblots. Running distance was similar between WT (3.98 ± 0.34 km; mean ± S.E.M.) and AMPK α2 KO mice (4.59 ± 0.36 km). Nampt expression did not change with training, but was lower in sedentary and trained α2 KO mice by 22 and 13 %, respectively (main effect, p<0.05). In the cohort receiving saline or AICAR, Nampt was also significantly (main effect, p<0.05) lower in the α2 KO mice. AICAR treatment increased Nampt expression in WT mice by 25% (p<0.05); this effect was completely abolished in the α2 KO animals. In conclusion, whole-body knockout of the AMPK α2 catalytic subunit reduces Nampt expression in mouse skeletal muscle. Furthermore, chronic AICAR treatment, but not prolonged exercise training increases Nampt protein expression in an AMPK α2-dependent manner.