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

Abstract

The findings show that food-derived molecules have the potential to influence skeletal muscle mass and function by regulating G protein-coupled receptor expression.

Genistein diet does not modify crypt morphology in the ob/ob mouse jejunum: a comparison of cryostat and clearing techniques

“…For example, in the same ob/ob mouse model, we have previously shown that 1) genistein diet has beneficial effects on energy expenditure, T 3 production, and corticosterone status in ob/ob males,17 2) genistein diet has been shown to rescue the number of acetylcholine receptors and decreases the distance between consecutive contractile events in jejunum from female ob/ob mice,16 3) genistein diet improves femur fracture resistance in response to bending loads in ob/ob females 22. Furthermore, literature evidence from others indicates that dietary genistein has a variety of other effects: 1) increases weight of gastrocnemius muscle in mice,23 2) modulates β 2 -adrenergic receptor expression in mouse skeletal muscle,24 3) ameliorates nonalcoholic fatty liver disease,25 4) has protective effects against neuronal degeneration in ApoE mice that fed a high-fat diet (Park et al26), and 5) attenuates intestinal architecture in broiler chicken following lipopolysaccharide-induced deterioration of intestinal morphology 27…”

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

“…GPCRs have a conserved core of seven transmembrane α-helices that are connected by three extracellular and intracellular loops. Some of these receptors are known as potent inducers of hypertrophy (Berdeaux and Stewart, 2012), and there is evidence about the importance of the regulation of the activation of GPCRs for the maintenance of skeletal muscle function (Chikazawa and Sato, 2018b). They transduce a signal from the extracellular environment to the intracellular ones.…”

“…A couple of recent studies by Sato, 2018a, 2018b) showed that it is also possible to increase muscle β2-ar expression by dietary improvement, so this was thought to be a promising strategy for the maintenance of healthy skeletal muscle and for achieving muscle hypertrophy. Resveratrol (a polyphenolic compound) and genistein (an isoflavone found in soybean) were shown to increase the β2-ar mRNA levels in skeletal muscle cells (Chikazawa and Sato, 2018b). Gramine (a natural indole alkaloid) and hordenine (an alkaloid of the phenethylamine class), if administered by intramuscular route, were shown to increase the expression of hypertrophic genes in mice quadriceps, which was suggested to have been mediated, at least in part, by the β2-ar activation, giving new possible therapeutic options (Chikazawa and Sato, 2018a…”

“…It has been widely accepted that activation of muscle β2-ars with the use of β2-ar agonists, principally divided in long-acting β2-agonists (LABAs) and short-acting β2-agonists (SABAs), leads to muscle hypertrophy and skeletal muscle repair in vivo (Chikazawa and Sato, 2018b;Jean-Baptiste et al, 2005;Sato et al, 2011).…”

“…SABAs, such as albuterol, were not found to generate the same impacts on muscle mass if administered orally, suggesting that drugs with a short halflife are not able to achieve these effects unless they are administered by intravenous route (Choo et al, 1992;Kamalakkannan et al, 2008). Indeed, the use by athletes of β2-ar agonists such as clenbuterol is strictly prohibited, and it would be considered a doping violation (Chikazawa and Sato, 2018b), since these drugs are banned by the World Anti-Doping Agency, though some are permissible under a therapeutic use exemption (such as for asthma).…”