Leptin upregulation in advanced multiple system atrophy with hypocholesterolemia and unexpected fat accumulation

Advanced multiple system atrophy (MSA) patients exhibit malnutrition with hypocholesterolemia and hypoalbuminemia, similar to patients with other neurodegenerative disorders, but also display unexpected fat accumulation. To understand this paradox, we herein examined the relationship between fat accumulation, measured by triceps skinfold thickness (TSF), and plasma leptin in 29 MSA patients at three clinical stages: activities of daily living (ADL) 1: ambulatory with/without wheelchair; ADL2: bedridden/communicable; and ADL3: bedridden/non-communicable. TSF and leptin were higher while cholesterol and albumin were lower in advanced stage ADL3 than in ADL1 or ADL2. Although a correlation was observed between leptin and TSF, a stepwise regression analysis identified the first significant positive predictor of leptin as the duration of autonomic symptoms (p < 0.005) rather than TSF. Leptin/TSF strongly correlated with the duration of autonomic symptoms (p < 0.001). These results implicate leptin resistance through autonomic dysfunction in the paradoxical fat accumulation observed in patients with advanced MSA, but not to be seen in the cholesterol metabolism.