Сytokine and matrix metalloproteinase profile in the skeletal muscle of rats with diet-induced obesity

Abstract

Background. Our previous studies revealed impaired contractile performance of skeletal muscle in diet-induced obesity, accompanied by intramyocellular lipid accumulation and signs of fibrosis. These findings suggest that obesity-related muscle dysfunction may result from activation of pro-fibrotic pathways and imbalance in extracellular matrix turnover driven by chronic low-grade inflammation – a hallmark of obesity pathogenesis. This study aimed to evaluate the effects of long-term high-fat feeding on the cytokine profile and matrix remodeling markers in rat skeletal muscle and to identify possible biochemical mechanisms underlying obesity-related muscle dysfunction. Materials and Methods. Adult male Wistar rats were fed either a standard chow (6.7 % fat; 15.27 kJ·g-1) or a high-fat diet (38.8 % fat; 28.71 kJ·g-1) for ten weeks. Serum biochemical parameters (total protein, glucose, cholesterol, bilirubin fractions, urea, creatinine, alanine and aspartate aminotransferases, α-amylase, alkaline phosphatase, γ-glutamyltransferase) were analyzed. Cytokines (TNF-α, IL-6, IL-1β, IL-10, IFN-γ), matrix metalloproteinases (MMP-2, MMP-9), and their inhibitor (TIMP-1) were quantified in skeletal muscle homogenates by ELISA. Results. A high-fat diet produced pronounced alterations in serum biochemical parameters, reflecting profound metabolic dysregulation and systemic impairment of homeostatic control. In skeletal muscle, obesity induced a significant rise in pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ) and a reduction in anti-inflammatory IL-10. These shifts were accompanied by increased MMP-2 and MMP-9 levels and a decline in TIMP-1, suggesting disturbed extracellular matrix turnover and early profibrotic remodeling. Conclusion. Diet-induced obesity promotes a sustained pro-inflammatory state accompanied by enhanced extracellular matrix remodeling. The imbalance between cytokines, metalloproteinases, and their inhibitor may underlie structural stiffening and decreased contractile efficiency of muscle fibers. A deeper understanding of these cytokine-MMP/TIMP interactions may provide new insights into the mechanisms of obesity-related muscle dysfunction and identify potential targets for maintaining skeletal muscle performance.