title: Proopiomelanocortin, agouti-related protein, and leptin in human cerebrospinal fluid: correlations with body weight and adiposity.
abstract: Leptin and its neuronal targets, which produce proopiomelanocortin (POMC) and agouti-related protein (AgRP), regulate energy balance. This study characterized leptin, POMC, and AgRP in the cerebrospinal fluid (CSF) of 47 healthy human subjects, 23 lean and 24 overweight/obese (OW/OB), as related to BMI, adiposity, plasma leptin, soluble leptin receptor (s-OB-R), and insulin. POMC was measured since the POMC prohormone is the predominant POMC peptide in CSF and correlates with hypothalamic POMC in rodents. Plasma AgRP was similarly characterized. CSF leptin was 83-fold lower than in plasma and correlated strongly with BMI, body fat, and insulin. The relative amount of leptin transported into CSF declined with increasing BMI, ranging from 4.5 to 0.52%, consistent with a saturable transport mechanism. CSF sOB-R was 78-fold lower than in plasma and correlated negatively with plasma and CSF leptin. CSF POMC was higher in lean vs. OW/OB subjects (P < 0.001) and correlated negatively with CSF leptin (r = -0.60, P < 0.001) and with plasma leptin, insulin, BMI, and adiposity. CSF AgRP was not different in lean vs. OW/OB; however, plasma AgRP was higher in lean subjects (P = 0.001) and correlated negatively with BMI, adiposity, leptin, insulin, and HOMA (P < 0.005). Thus, CSF measurements may provide useful biomarkers for brain leptin and POMC activity. The striking negative correlation between CSF leptin and POMC could be secondary to leptin resistance and/or neuronal changes associated with obesity but may also indicate that POMC plays a primary role in regulating body weight and adiposity. The role of plasma AgRP as a neuroendocrine biomarker deserves further study.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York;
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Page-Wilson
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York;
authors.forename: Kana
authors.initials: K
authors.lastname: Meece
authors.affiliation: Faculties of Life Sciences and Medical and Human Sciences, University of Manchester, Manchester, United Kingdom;
authors.forename: Anne
authors.initials: A
authors.lastname: White
authors.affiliation: Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosenbaum
authors.affiliation: Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York; and.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Smiley
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; sw22@cumc.columbia.edu.
authors.forename: Sharon L
authors.identifier: http://orcid.org/0000-0002-9659-7360
authors.initials: SL
authors.lastname: Wardlaw
mesh_terms: D050154:Adiposity; D000328:Adult; D054369:Agouti-Related Protein / Q000097:blood / Q000134:cerebrospinal fluid*; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000134:cerebrospinal fluid*; D050177:Overweight / Q000134:cerebrospinal fluid; D011333:Pro-Opiomelanocortin / Q000134:cerebrospinal fluid*; D054411:Receptors, Leptin / Q000097:blood; D055815:Young Adult
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D007328:Insulin; D020738:Leptin; D054411:Receptors, Leptin; D011333:Pro-Opiomelanocortin
keywords: agouti-related protein; cerebrospinal fluid; leptin; proopiomelanocortin