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.

Metabolic syndrome (MetS) is associated with ectopic fat deposition, chronic systemic inflammation, oxidative stress, and increased susceptibility to organ dysfunction. While its cardiovascular consequences have been extensively studied, pulmonary al-terations remain less well characterized, particularly with respect to ferropto-sis-regulatory pathways. In this study, we evaluated ectopic fat deposition, TLR4/NF-κB signaling pathway, and ferroptosis-regulatory markers in a MetS rat model and analyzed the therapeutic potential of combined resveratrol plus quercetin (combined R + Q) supplementation. Rats were maintained for five months with 30% sucrose in drinking water to induce MetS and subsequently treated for 4 weeks with the R + Q combination (50 and 0.95 mg/kg/day, respectively). Lung tissue was analyzed by fluorescence microscopy to assess fat deposition, by colorimetric histology to evaluate hemosiderin-containing cells, including the quantification of hemosiderin-laden macrophages (HLMs), and by immunoblotting to determine TLR4, p-p65, and glutathione peroxidase 4 (GPX4), as well as cystine/glutamate antiporter SLC7A11 (xCT) protein expression. Lungs from MetS rats exhibited significantly higher fat deposits, pathological HLMs accumulation, upregulated TLR4/p-p65 signaling, elevated compensatory GPX4 expression, and depressed xCT levels compared with controls. Notably, the combined R + Q treatment markedly attenuated alterations in TLR4/NF-κB signaling and successfully restored xCT expression (p = 0.0116), stabilizing pulmonary redox homeostasis and limiting overall tissue susceptibility to lipotoxic injury.