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%u010ceskoslovensk%u00e1 fyziologie 73/2025 %u010d. 2 35P%u0158EHLEDN%u00c9 %u010cL%u00c1NKYet al., 2012). Feutin-A induces triglyceride accumulation in hepatocytes, and consequently, patients with MASLD have higher levels of serum fetuin-A (Seo et al., 2021). It is also a proinflammatory cytokine that also reduces muscle glucose uptake (Seo et al., 2021). Unlike fetuin-A, FGF21 is a hepatokine that was found to have a metabolic protective role in animal models of MASLD. Although not fully investigated in humans, it has been confirmed that it reduces plasma glucose and lipid levels once injected in obese and diabetic rats accompanied by an improvement of insulin sensitivity in both the liver and the skeletal muscle (Kliewer & Mangelsdorf, 2019). The protective role of FGF21 can potentially help counteracting the disease in rats, however, these positive effects decline in advanced stages of the disease (Kliewer & Mangelsdorf, 2019).Another important hepatokine is ANGPTL4, which modulates lipid metabolism by halting lipoprotein lipase, causing a reduction in fatty acid and lipid uptake in peripheral tissues (Jensen-Cody & Potthoff, 2021). While this may be beneficial for the liver as it prevents excessive lipotoxicity in MASLD, it exacerbates insulin resistance and fat deposition in skeletal muscle (Seo et al., 2021).Muscle-liver-fat signalling axisAdipokines are another group of signalling molecules secreted by adipose tissue that influence both liver and muscle tissue. Together with hepatokines and myokines they form the muscle-liver-fat axis. The most investigated adipokines are leptin and adiponectin. Leptin suppresses appetite and increases energy expenditure. It also regulates glucose and lipids utilization in skeletal muscles and reduces lipid accumulation in hepatocytes through activation of %u03b2-oxidation (de Oliveira Dos Santos et al., 2021). However, in metabolic syndrome and obesity, leptin resistance develops leading to elevated serum leptin levels. This eventually results in major dysregulation of glucose and lipids metabolism in both the liver and skeletal muscle (Gonzalez-Gil & Elizondo-Montemayor, 2020). In addition, leptin has a pro-fibrogenic and pro-inflammatory effect on the liver that is related to the progression of MASLD (Merli, Lattanzi & Aprile, 2019). On the other hand, adiponectin has an anti-inflammatory and anti-fibrotic function that positively influences the liver during the pathogenesis of MASLD (de Oliveira Dos Santos et al., 2021). It also increases insulin sensitivity and enhances fatty acid oxidation. Oppositely, low blood adiponectin level is strongly correlated with liver disease progression and with deteriorated glucose metabolism in muscles (Buechler et al., 2017). Therapeutic interventions for muscle atrophy in MASLDMASLD patients commonly develop muscle atrophy during the progression of the disease. This phenomenon is promoted by MASLD pathophysiological complexes, such as insulin resistance and systemic chronic inflammation. Additionally, the dysfunctions in muscular signalling pathways and the generalized catabolic state of muscles all lead to the development of muscle atrophy (Kuchay et al., 2022). Combating muscle atrophy in MASLD involves a combination of therapeutic approaches targeted towards the pathophysiological process in MASLD, including mitochondrial function and the generalized inflammatory state and oxidative stress in the body. Regular exercise, including both aerobic and resistance training, enhances mitochondrial health which is protective to the muscles during the progression of MASLD (Chen et al., 2023). Physical activity promotes mitochondrial resynthesis and reduces inflammation through key signalling pathways like IGF-1/PI3K/Akt/mTOR. Pharmacological interventions also are valid. Antioxidants, such as resveratrol and mitoquinone Q, target oxidative stress and generally benefit the systematic and hepatic mitochondrial health. Mitochondria targeted gene and cell therapies provide novel and clever solutions that have proven effective. (Chen et al., 2023). Nutritional management also plays a positive role. Proper intake of nutrients, including amino acids, omega-3 fatty acids, and essential vitamins, improves mitochondrial function and muscular protein synthesis. Pharmacological options may also include ursodeoxycholic acid (UDCA) which not only regulates apoptosis and programmed cell death in the liver but also exerts well documented antioxidant properties (Delli Bovi et al., 2021). Lifestyle modifications, such as weight management, alcohol, and smoking cessation, also have a great beneficial impact. These changes not only improve mitochondrial and muscle function, but also combat metabolic risk factors associated with MASLD. CONCLUSION MASLD is a multidimensional metabolic disorder defined by complex interactions between the liver and the body organs. The pathophysiological process of MASLD begins with the excessive accumulation of lipids in the liver which consequently promotes damage through oxidative stress and inflammation and results in conditions such as steatohepatitis and fibrosis. Signalling modulators secreted from the liver, skeletal muscle, and adipose tissue facilitate the crosstalk between the liver and muscle tissues. Understanding the function these molecules is crucial for comprehending the complex interactions occurring between organs, and subsequently providing targeted treatment approaches. Exercise as well as pharmacological means targeting MASLD complex pathways has been proven effective in halting the disease progression. FundingThis work was supported by the project SVV-2023-260656.Declaration of generative AI and AI-assisted technologies in the writing process. During the preparation of this work the authors used ChatGpt in order to check grammar. After using this tool the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.Moustafa Elkalaf M.B.B.Ch., Ph.D.Charles UniversityFaculty of Medicine in Hradec Kr%u00e1lov%u00e9Department of Physiology%u0160imkova 870500 03 Hradec Kr%u00e1lov%u00e9e-mail: elkalafm@lfhk.cuni.cz