Abstract
β2-Adrenergic receptor ( Adrβ2 ) is the most abundant form of adrenergic receptors in skeletal muscle. Our previous studies have shown that the ventromedial hypothalamic nucleus (VMH) regulates metabolic benefits of exercise, potentially by skeletal muscle Adrβ2 . Although a large body of literature has shown the importance of Adrβ2 on skeletal muscle physiology, it remains unexplored whether skeletal muscle Adrβ2 contributes to metabolic benefits of exercise, such as prevention of diet-induced obesity (DIO). Here, we generated mice lacking Adrβ2 in skeletal muscle cells (SKM (Adrβ2) ) and tested whether SKM (Adrβ2) is required for metabolic benefits of exercise on DIO. Deletion of SKM (Adrβ2) completely abolished the induction of peroxisome proliferator-activated receptor gamma coactivator 1-alpha ( Pgc-1α ) in skeletal muscle by β2-agonist, which is a potent activator of Pgc-1α . Exercise upregulates Pgc-1α, which regulates a broad range of skeletal muscle physiology, including hypertrophy and mitochondrial function. Deletion of SKM (Adrβ2) hampers augmented Pgc-1α in skeletal muscle by a single bout of exercise. Intriguingly, we found that deletion of SKM (Adrβ2) increased endurance capacity. Further, our data showed that body weight in DIO mice lacking SKM (Adrβ2) is comparable to that of control DIO mice during exercise training, suggesting that deletion of SKM (Adrβ2) did not affect the metabolic benefits of exercise in DIO. Collectively, our data indicate that SKM (Adrβ2) contributes to exercise-induced transcriptional changes and endurance capacity, however, it is not required for exercise benefits on bodyweight in DIO mice.