Metabolic dysfunction-associated steatotic liver disease in spinal cord injury and obesity: A narrative review of divergent mechanisms, convergent outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is most frequently attributed to obesity. However, spinal cord injury (SCI) also induces a rapidly developing MASLD phenotype in the absence of obesity. This narrative review synthesizes emerging evidence to compare neurogenic and obesogenic drivers of MASLD (neurogenic MASLD vs obesity-associated MASLD [oMASLD]) to uncover mechanistic pathways that converge on liver injury despite markedly different initiating stimuli. While neurogenic MASLD is characterized by abrupt and pronounced sympathetic nervous system dysregulation, oMASLD also shows chronic sympathetic overactivity driven by hyperinsulinemia and adipose dysfunction, highlighting sympathetic nervous system imbalance as a mechanistic intersection linking both etiologies. This review also discusses how oMASLD onset contrasts with the acute sympathetic dysregulation, inflammation, and multi‑organ metabolic disturbances leading to neuro‑MASLD. By integrating liver‑specific mechanisms with adipose, gastrointestinal, and autonomic pathways, we identify how neurogenic signals may potentiate or mimic obesogenic pathways. Thus, understanding neuro‑MASLD provides unique insight into the early, obesity‑independent instigators of MASLD, which may help to explain why individuals with SCI, despite being normal weight at the time of injury, develop cardiometabolic dysfunction and premature mortality. The comparative framework presented here also offers a mechanistic foundation for considering nutritional strategies targeting gut barrier integrity, inflammation, and mitochondrial function, all of which are critically understudied in SCI. Leveraging neuro‑MASLD to identify actionable neuroimmune-metabolic intersections may accelerate the development of precision nutrition interventions relevant to both neurogenic and obesogenic MASLD.