Resveratrol Attenuates Fibrosis and Alters Signaling Pathways in Diabetic Cardiac and Skeletal Muscle, and Adipose Tissue without Reversing the Structural Damage

• DOI: 10.20944/preprints202501.0940.v1
• Publication Date: 2025-01-14T03:20:53Z
• Authors: Célia Maria Cássa...; Alessandra Roggerio; Paula Lázara Cruz; Luiz Alberto Benv...; Maria Cláudia Iri...; Antonio de Padua ...

Resveratrol (RSV) improves metabolic and cardiovascular functions, but its tissue-specific effects on diabetes remain unclear. This study investigated RSV's impact on cardiac and skeletal muscle and adipose tissue in a rat diabetes model. Thirty-two Wistar rats were assigned to four groups: control (C), control treated with RSV (RC), diabetic (D), and diabetic treated with RSV (RD). Diabetes was induced using streptozotocin and nicotinamide. After two weeks, RC and RD groups received RSV for six weeks. Histological and protein expression analyses were performed on cardiac, skeletal muscle, and visceral fat tissues. RSV significantly reduced collagen accumulation in diabetic cardiac and skeletal muscles compared to untreated diabetic rats. Adipose tissue in diabetic rats exhibited the most notable reduction in collagen levels following RSV treatment (D/C: 30.15, IQ: 9.66–50.36 vs. RD/C: 8.88, IQ: 4.86–19.06, p < 0.01).In cardiac tissue, RSV downregulated AKT and rpS6 phosphorylation. In skeletal muscle, RSV suppressed rpS6 phosphorylation and in adipose tissue, RSV enhanced mTOR and PPARα expression. RSV reduced receptor for advanced glycation end products expression across all examined tissues, indicating its role in modulating pathways driven by hyperglycemia. Although RSV improved fibrosis and signaling pathways, it did not reverse structural damage or metabolic dysfunction. These results highlight the need for further studies to refine RSV-based therapies for diabetes-induced tissue damage.