Continuous 24-Hour Proopiomelanocortin, Leptin, and Amino Acid Measurements in Human Cerebrospinal Fluid: Correlations with Plasma Leptin, Soluble Leptin Receptor and Amino Acid Levels

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-649
Sharon L Wardlaw*1, Charles F Burant2, Samuel Klein3, Kana Meece1, Anne White4 and Randall J Bateman5
1Columbia University College of Physicians & Surgeons, New York, NY, 2University of Michigan Medical School, Ann Harbor, MI, 3Washington Univ Schl of Med, Saint Louis, MO, 4University of Manchester, Manchester, United Kingdom, 5Washington University School of Medicine, St Louis, MO
In order to characterize diurnal changes in central leptin and its target neuropeptide, proopiomelanocortin (POMC), we have measured leptin and POMC in cerebrospinal fluid (CSF) as related to changes in plasma leptin and soluble leptin receptor (SLR) levels. We have also measured CSF and plasma levels of 20 amino acids (AA) as AA can affect brain POMC.  Stored CSF and plasma samples were obtained from 8 healthy subjects (5M,3F) aged 23-49, BMI 23-33, who served as controls for an Alzheimer disease study. CSF was collected hourly over a 24-36h period via indwelling subarachnoid catheter.  Plasma was collected every 1-2h. CSF leptin and POMC were measured by sensitive ELISA.  The POMC ELISA detects POMC prohormone, the predominant POMC peptide in CSF.  There was a diurnal rhythm for plasma leptin with a peak at 10pm (144% of baseline); there was a similar rhythm for leptin in CSF with a peak (117%) 3-5h after the plasma peak. A strong positive correlation was noted between plasma and CSF leptin (r=0.810, p<0.001) when CSF levels were shifted to correct for the 5h time delay of CSF flow to the lumbar intrathecal space.  Plasma SLR levels were lowest between 1 and 3 am when plasma and CSF leptin levels were elevated.  A strong negative correlation between plasma SLR and CSF leptin was noted (r=-0.941), consistent with animal data showing that SLR inhibits transport of leptin into the brain, and suggests that during the night, lower levels of SLR may enhance leptin transport into the brain in humans.  A consistent diurnal rhythm for POMC in CSF was also detected with the highest levels (125% of baseline) between 11pm-2am. Diurnal changes in POMC expression have also been found in the rodent hypothalamus that correspond to their leptin rhythm. In fact there was a good correlation (r= 0.755) between CSF POMC and CSF leptin concentrations in individual subjects studied over  24h.  CSF AA levels also increased at night, including changes in branched chain AA which increased by 175 to 597% in the 8 subjects.  The magnitude of these changes appears large enough to influence metabolic and signaling pathways in the brain and may impact on the nocturnal changes in POMC levels. These studies show that there are diurnal changes in leptin and POMC in human CSF that likely reflect changes in central leptin and melanocortin activity.  Our results suggest that nocturnal elevations in leptin, AA and POMC levels may help to suppress appetite and decrease feeding at night.

Nothing to Disclose: SLW, CFB, SK, KM, AW, RJB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Atkins Foundation, NIH DK093920
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