Molecular and cellular mechanisms of muscle-adipose tissue crosstalk driving sarcopenic obesity: an integrative review of human, animal, and in vitro models.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Sarcopenic Obesity is a complex geriatric syndrome that is not simply the co-occurrence of sarcopenia and obesity but is a synergistic pathophysiological relationship in which the sum of the risk factors is greater than the sum of the individual conditions. This integrative review proposes that sarcopenic obesity is fundamentally an illness of impaired bidirectional communication between skeletal muscle and adipose tissue that function as dynamic endocrine organs that interact through a vast repertoire of bioactive molecules. We critically analyze the molecular signaling pathways responsible for this crosstalk and the simultaneous hyperactivation of the Ubiquitin-Proteasome System and NF-κB pathways. Furthermore, highlighting the paradigm-shifting role of the Exosomal miRNA Regulatory Network, we explored how adipose-derived extracellular vesicles deliver atromiRs (e.g., miR-27a, Let-7d-3p) to myocytes and cause insulin resistance and regenerative failure, and the loss of myocyte-derived miR-146a-5p eliminates an important brake on adipogenesis. Also, we explored cellular mechanisms such as macrophage phenotypic switching (metaflammation), mitochondrial lipotoxicity, and the newly emerging gut-microbiota-muscle axis. Finally, we explored advanced experimental models, such as organ-on-a-chip systems, and explored the clinical paradox of GLP-1 receptor agonist-induced muscle loss

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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