A Combination of Resveratrol and Quercetin Prevents Sarcopenic Obesity: Its Role as a Signaling Inhibitor of Myostatin/ActRIIA and ActRIIB/Smad and as an Enhancer of Insulin Actions

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Abstract
Sarcopenic obesity (SO), characterized by an excess of fat and a decrease in muscle strength or mass, is a global public health concern and is linked to metabolic conditions such as metabolic syndrome (MetS). Different mechanisms contribute to SO, such as inflammation, fatty acid infiltration, and insulin resistance (IR). Recently, myostatin (MYOST), an inhibitory factor for skeletal muscle tissue, was proposed as an aimed compound for the treatment of conditions of muscular metabolic imbalance mass and MetS. On the other hand, a therapy with natural compounds such as resveratrol (R) and quercetin (Q) is effective for the treatment of MetS, but its effect on the MYOST pathway has been poorly explored. The control group received water, and the MetS group received 30% commercial sugar in the drinking water for 6 months. Polyphenol mix (R at a dose of 50 mg/kg/day and Q at 0.95 mg/kg/day) was administered for 1 month. MetS rats present SO linked to an increase in the expression of MYOST/ActRIIA and ActRIIB (p < 0.0001). R+Q treatment prevented SO by lowering the expression of MYOST and its receptors and increased the expression of Smad 7 in MetS rats (p < 0.0001). Moreover, the polyphenol treatment reverted IR by increasing Akt phosphorylation, leading to an increase in muscle mass. It decreased lipid stores, restored glycogen accumulation, and increased myosin expression (p < 0.0001). The results of this work indicate that R+Q supplementation could be a promising therapeutic agent to prevent SO and sarcopenia derived from other metabolic alterations.

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