Lipedema and Dynapenia: Inflammatory Myosteatosis as a Mechanistic Link Between Tissue Expansion and Muscle Dysfunction

Background: Lipedema is a chronic, progressive adipose tissue disorder that affects almost exclusively women and is characterized by disproportionate limb fat accumulation, pain, edema, and resistance to conventional weight-loss strategies. Although traditionally approached as a disorder of adipose tissue expansion, emerging evidence suggests that functional impairment in advanced lipedema cannot be fully explained by fat pathology alone. Methods: This hypothesis-driven review proposes a novel conceptual framework in which advanced lipedema is accompanied by a parallel failure of skeletal muscle function, characterized by dynapenia despite preserved or increased limb volume. Results: Our findings indicate a phenotype characterized by reduced muscle strength and quality in advanced lipedema, which we term lipedemata dynapenic myosteatosis. We synthesize clinical, imaging, and mechanistic data indicating that inflammatory myosteatosis, mitochondrial dysfunction, and impaired lipid oxidation contribute to reduced muscle quality and exercise intolerance in late-stage lipedema, particularly Stage 3, while emphasizing that functional decline should be proactively investigated from Stage 2 onward. Within this context, conventional resistance exercise, while physiologically required to prevent dynapenia, may be poorly tolerated due to inflammation, edema, and pain, creating a therapeutic deadlock. To address this paradox, we present a hypothesis-generating dual-target framework that integrates metabolic modulation aimed at restoring mitochondrial fatty-acid oxidation with anabolic signaling directed toward contractile tissue, drawing mechanistic analogies from established catabolic states. Conclusions: Importantly, this model is presented as a conceptual and translational framework rather than a clinical recommendation. By shifting the focus from adipose volume to muscle quality and function, this work reframes advanced lipedema as a disorder of coupled adipose–muscle bioenergetic failure. Future clinical studies are required to validate this framework, with outcomes centered on strength, mobility, pain, and functional independence rather than weight loss alone.