Identification of Functional Food Factors as β₂-Adrenergic Receptor Agonists and Their Potential Roles in Skeletal Muscle

Abstract

Maintaining skeletal muscle functions by controlling muscle metabolism is of utmost importance. β-Adrenergic receptor (β-AR), which is expressed in skeletal muscle, is a member of the G-protein-coupled receptor family that plays a critical role in the maintenance of muscle mass. In the present study, using luciferase reporter assays in β-AR-expressing HEK293 cells, we discovered several food factors that exhibited agonistic activity at mouse or human β-AR. Osthole, gramine, and hordenine were identified as both mouse and human β-AR agonists, whereas berberine was identified as a mouse β-AR agonist only. Additionally, intramuscular injection of gramine or hordenine in mice facilitated gene expression of several cAMP response element binding protein targets, which is thought to result in increased skeletal muscle protein synthesis. This study provides evidence that several food factors might exert potential health effects on skeletal muscle by enhancing cAMP signaling through the activation of β-AR.

Identification of a Novel Function of Resveratrol and Genistein as a Regulator of β2‐Adrenergic Receptor Expression in Skeletal Muscle Cells and Characterization of Promoter Elements Required for Promoter Activation

“…To assess food factors that boost β 2 ‐AR promoter activity, we performed luciferase assays using a reporter gene positioned within −1500 to +1 nucleotides of the mouse β 2 ‐AR promoter region. A total of 357 purified in‐house food factors were used as test compounds . C2C12 myoblast cells were transfected with the reporter plasmid and then cultured with one of the food factors at 100 µ m for 24 h. Subsequently, we selected food factors that fulfilled the following requirements: 1) those that elevated luciferase activity more than 2.5‐fold compared to the control group and 2) those that elevated endogenous β 2 ‐AR mRNA levels in the C2C12 cells.…”

Taurine Stimulates Thermoregulatory Genes in Brown Fat Tissue and Muscle without an Influence on Inguinal White Fat Tissue in a High-Fat Diet-Induced Obese Mouse Model

“…Meanwhile, ARDB2, which is highly expressed in skeletal muscle, plays a critical role in the maintenance of muscle mass by enhancing cAMP signaling through the activation of ADRB2. Several food factors are known to show agonistic activity at mouse or human ADRB2 [ 54 ]. Taurine also has potential to modulate the expression of ADRBs in tissues.…”

The effects of beta (2)-adrenergic receptors activation on the cardiovascular system and on the skeletal muscle: A narrative review

“…Skeletal muscle mass is controlled by balancing protein synthesis and degradation (Chikazawa & Sato, 2018a). Decreased protein synthesis and/or increased protein degradation for a prolonged period of time, which may be caused by inactivity, inadequate diet, reduced hormone levels or disease, contribute to a decrease in skeletal muscle mass and the onset of atrophy (Chikazawa & Sato, 2018a;Toledo et al, 2016).…”

“…β2-ar agonist clenbuterol administration was found to improve skeletal muscle atrophy induced by hindlimb unweighting, denervation, and dexamethasone treatment through the activation of protein synthesis and inhibition of protein degradation by controlling lysosomal and proteasomal activity in animal models (Chikazawa and Sato, 2018a;Gonçalves et al, 2011;Pellegrino et al, 2004;Yimlamai et al, 2005).…”