Unveiling the gut-muscle-adipose axis in sarcopenic obesity: mechanisms of inter-organ crosstalk and perspectives on GLP-1-based therapeutics

Abstract

Sarcopenia, an age-related loss of muscle mass, strength, and function, reflects failing inter-organ communication. Using sarcopenic obesity (SO) as a model, this review details multi-organ breakdown across three channels: hormonal (declining gut microbial metabolites weakening muscle TGR5/FXR signaling), neural (altered vagal afferent and sympathetic outflow), and immune/cytokine (visceral fat inflammation impairing insulin signaling, while ectopic myocyte lipids trigger MuRF1-mediated muscle breakdown). GLP-1 receptor agonists highlight network fragility, as aggressive therapy strips 20–40% of weight loss from lean tissue. Synthesizing evidence published from January 2000 to July 2026, including clinical and preclinical studies, clinical trials and trial-derived analyses, together with the 2022 ESPEN/EASO consensus criteria, we argue that modeling inter-organ communication must reshape SO diagnosis and combination therapeutics.

Keywords: Sarcopenic obesity, gut-muscle axis, GLP-1 receptor agonists, inter-organ crosstalk, vagal afferent signaling, skeletal muscle atrophy