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.
BACKGROUND
The novel adipokine, nesfatin-1/NUCB-2, reduces food intake, levels of which are elevated in overweight individuals.


OBJECTIVE
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.


METHODS
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.


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/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].


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.
Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
Bee K
BK
Tan
Manfred
M
Hallschmid
Werner
W
Kern
Hendrik
H
Lehnert
Harpal S
HS
Randeva
D050154:Adiposity / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D015992:Body Mass Index; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D009765:Obesity / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D036361:Peptide Hormones / Q000032:analysis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D012527:Satiation / Q000502:physiology; D055815:Young Adult
D019440:Anti-Obesity Agents; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D036361:Peptide Hormones