Molecular and cellular mechanisms of muscle–adipose tissue crosstalk driving sarcopenic obesity: an integrative review of human, animal, and in vitro models
- 1Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, Egypt. [email protected]
- 2Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, Egypt
Abstract
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. We conclude that future therapeutic frontiers are in the area of combination therapies and miRNA mimics to reinstate this broken molecular dialogue.
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BibTeX
@article{seliem2026molecular,
title = {{Molecular and cellular mechanisms of muscle–adipose tissue crosstalk driving sarcopenic obesity: an integrative review of human, animal, and in vitro models}},
author = {Mahmoud A. Seliem and Mamdouh A. Ragab},
journal = {Nutrition \& Metabolism},
year = {2026},
month = may,
doi = {10.1186/s12986-026-01123-2},
url = {https://doi.org/10.1186/s12986-026-01123-2},
note = {CC BY},
}
RIS
TY - JOUR
TI - Molecular and cellular mechanisms of muscle–adipose tissue crosstalk driving sarcopenic obesity: an integrative review of human, animal, and in vitro models
AU - Mahmoud A. Seliem
AU - Mamdouh A. Ragab
PY - 2026
DA - 2026/05/13
JO - Nutrition & Metabolism
DO - 10.1186/s12986-026-01123-2
UR - https://doi.org/10.1186/s12986-026-01123-2
AB - 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. We conclude that future therapeutic frontiers are in the area of combination therapies and miRNA mimics to reinstate this broken molecular dialogue.
SN - 1743-7075
ER -