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

Abstract

Abstract Context: The novel adipokine, nesfatin-1/NUCB-2, reduces food intake, levels of which are elevated in overweight individuals. Objectives: 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. Design: 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/m2] and correlated to body adiposity and metabolic parameters. Results: 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/m2; R = 0.744; P = 0.002) and obese (BMI ≥30 kg/m2; 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/m2; P < 0.01], and fat mass [32.8 (29.5–40.6) vs. 30.7 (8.2–20.1) kg/m2; P < 0.01]. Conclusions: 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.