Document Detail


Cerebrospinal fluid levels of leptin, proopiomelanocortin, and agouti-related protein in human pregnancy: evidence for leptin resistance.
MedLine Citation:
PMID:  23118421     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: 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.
DESIGN AND PARTICIPANTS: 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:
Gabrielle Page-Wilson; Elena Reitman-Ivashkov; Kana Meece; Anne White; Michael Rosenbaum; Richard M Smiley; Sharon L Wardlaw
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-01
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  98     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-03-07     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  264-71     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Agouti-Related Protein / cerebrospinal fluid*
Body Mass Index
Case-Control Studies
Drug Resistance / physiology
Energy Metabolism / physiology
Fasting / blood,  cerebrospinal fluid,  metabolism
Female
Humans
Immunochemistry
Leptin / blood,  cerebrospinal fluid*,  metabolism*
Pregnancy / blood,  cerebrospinal fluid*,  metabolism
Pro-Opiomelanocortin / cerebrospinal fluid*
Receptors, Leptin / blood,  metabolism
Grant Support
ID/Acronym/Agency:
DK093920/DK/NIDDK NIH HHS; R01 DK064773/DK/NIDDK NIH HHS; R01 DK093920/DK/NIDDK NIH HHS; TR000040/TR/NCATS NIH HHS; UL1 RR024156/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Agouti-Related Protein; 0/Leptin; 0/Receptors, Leptin; 66796-54-1/Pro-Opiomelanocortin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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