Decreased cerebrospinal fluid/plasma ratio of the novel satiety molecule, nesfatin-1/NUCB-2, in obese humans: Evidence of nesfatin-1/NUCB-2 resistance and implications for obesity treatment

CONTEXT: The novel adipokine, nesfatin-1/NUCB-2, reduces food intake, levels of which are elevated in overweight individuals.\n\nOBJECTIVES: The aim of the study was to investigate the mechanisms underlying brain nesfatin-1/NUCB-2 uptake and to determine whether reduced uptake may contribute to nesfatin-1/NUCB-2 resistance.\n\nDESIGN: Cerebrospinal fluid (CSF) and corresponding plasma nesfatin-1/NUCB-2 were measured by ELISA [18 men and 20 women; age, 19-80 yr; body mass index (BMI), 16.2-38.1 kg/m(2)] and correlated to body adiposity and metabolic parameters.\n\nRESULTS: CSF/plasma nesfatin-1/NUCB-2 ratio was significantly negatively associated with BMI, body weight, fat mass, and CSF glucose. BMI was predictive of CSF/plasma nesfatin-1/NUCB-2 ratio (β = -0.786; P = 0.045). CSF nesfatin-1/NUCB-2 was significantly positively associated with plasma nesfatin-1/NUCB-2 (R = 0.706; P < 0.01). There was a significant linear relation between CSF and plasma nesfatin-1/NUCB-2 in lean (BMI <25 kg/m(2); R = 0.744; P = 0.002) and obese (BMI ≥ 30 kg/m(2); R = 0.693; P = 0.026) subjects. Subjects in the highest plasma nesfatin-1/NUCB-2 quintile had lower CSF/plasma nesfatin-1/NUCB-2 ratio [26.5% (26.0-29.5%)] compared to the lowest plasma nesfatin-1/NUCB-2 quintile [38.5% (34.0-42.0%)] (P < 0.01), corresponding BMI [32.4 (31.0-35.0) vs. 23.3 (19.7-23.5) kg/m(2); P < 0.01], and fat mass [32.8 (29.5-40.6) vs. 30.7 (8.2-20.1) kg/m(2); P < 0.01].\n\nCONCLUSIONS: Our observations have important implications with respect to the potential weight-reducing actions of nesfatin-1/NUCB-2 treatment. Future research should seek to clarify whether nesfatin-1/NUCB-2 would be beneficial in the management of obesity.