title: Cerebrospinal fluid levels of leptin, proopiomelanocortin, and agouti-related protein in human pregnancy: evidence for leptin resistance.
abstract: BACKGROUND
  Leptin suppresses appetite by modulating the expression of hypothalamic neuropeptides including proopiomelanocortin (POMC) and agouti-related peptide (AgRP). Yet during pregnancy, caloric consumption increases despite elevated plasma leptin levels.
  
  
  METHODS
  To investigate this paradox, we measured leptin and soluble leptin receptor in plasma and leptin, POMC, and AgRP in cerebrospinal fluid (CSF) from 21 fasting pregnant women before delivery by cesarean section at a university hospital and from 14 fasting nonpregnant women.
  
  
  RESULTS
  Prepregnancy body mass index was 24.6 ± 1.1 (SE) vs. 31.3 ± 1.3 at term vs. 26.5 ± 1.6 kg/m(2) in controls. Plasma leptin (32.9 ± 4.6 vs. 16.7 ± 3.0 ng/ml) and soluble leptin receptor (30.9 ± 2.3 vs. 22.1 ± 1.4 ng/ml) levels were significantly higher in pregnant women. However, mean CSF leptin did not differ between the two groups (283 ± 34 vs. 311 ± 32 pg/ml), consistent with a relative decrease in leptin transport into CSF during pregnancy. Accordingly, the CSF/plasma leptin percentage was 1.0 ± 0.01% in pregnant subjects vs. 2.1 ± 0.2% in controls (P < 0.0001). Mean CSF AgRP was significantly higher in pregnant subjects (32.3 ± 2.7 vs. 23.5 ± 2.5 pg/ml; P = 0.03). Mean CSF POMC was not significantly different in pregnant subjects (200 ± 13.6 vs. 229 ± 17.3 fmol/ml; P = 0.190). However, the mean AgRP/POMC ratio was significantly higher among pregnant women (P = 0.003), consistent with an overall decrease in melanocortin tone favoring increased food intake during pregnancy.
  
  
  CONCLUSIONS
  These data demonstrate that despite peripheral hyperleptinemia, positive energy balance is achieved during pregnancy by a relative decrease in central leptin concentrations and resistance to leptin's effects on target neuropeptides that regulate energy balance.
authors.affiliation: Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Page-Wilson
authors.forename: Elena
authors.initials: E
authors.lastname: Reitman-Ivashkov
authors.forename: Kana
authors.initials: K
authors.lastname: Meece
authors.forename: Anne
authors.initials: A
authors.lastname: White
authors.forename: Michael
authors.initials: M
authors.lastname: Rosenbaum
authors.forename: Richard M
authors.initials: RM
authors.lastname: Smiley
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Wardlaw
mesh_terms: D000328:Adult; D054369:Agouti-Related Protein / Q000134:cerebrospinal fluid*; D015992:Body Mass Index; D016022:Case-Control Studies; D004351:Drug Resistance / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D007120:Immunochemistry; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D011247:Pregnancy / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000134:cerebrospinal fluid*; D054411:Receptors, Leptin / Q000097:blood / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D020738:Leptin; D054411:Receptors, Leptin; D011333:Pro-Opiomelanocortin