Lymphatic dysfunction and impaired interstitial clearance in sarcopenic obesity: a hypothesis-generating review

Sarcopenic obesity (SO) is characterized by excess adiposity together with reduced skeletal muscle mass and impaired muscle function, and primarily affects older adults. Its pathogenesis involves chronic low-grade inflammation, insulin resistance, ectopic lipid accumulation, mitochondrial dysfunction, and disrupted skeletal muscle homeostasis. Current models mainly explain how inflammatory and metabolic signals are generated through adipose-muscle crosstalk, but less clearly address why these signals persist within the local interstitial environment. The lymphatic system maintains interstitial homeostasis by regulating tissue drainage, mediator clearance, immune trafficking, lipid transport, and microenvironmental renewal. In SO, ageing and obesity may jointly impair lymphatic function: obesity increases inflammatory, lipid, and metabolic lymphatic stress, whereas ageing lowers baseline lymphatic reserve. These abnormalities may sustain a pro-inflammatory, pro-lipotoxic, and repair-unfavorable interstitial milieu. In this review, we summarize ageing- and obesity-associated lymphatic abnormalities and propose a clearance-centered framework in which impaired lymphatic clearance amplifies local inflammation, lipid stress, insulin resistance, gut-muscle axis disturbance, and defective skeletal muscle repair in SO. Skeletal muscle deterioration may further weaken contraction-assisted lymphatic return, potentially reinforcing impaired clearance and local inflammatory-metabolic stress. This framework complements the adipose-muscle crosstalk model and highlights testable directions for future SO-specific studies.