Leptin Distribution in the Gut of Male Mice

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-665
Robert Allan Hart*1 and James Robert McFarlane2
1University of New England, Armidale, NSW, Australia, 2Univ of New England, Armidale NSW, Australia
Leptin, the product of the Ob gene, was originally thought to be synthesised exclusively by adipose tissue, entering the circulation to signal primarily at the hypothalamus to regulate energy turnover. However, there have been several studies which suggest that little circulating leptin enters the brain, suggesting it may not be the major target of leptin, and that leptin may have important roles in tissues outside of the central nervous system. Others have shown that leptin is produced in the stomach and that its receptors are located along the gut, suggesting a potential role in the digestive tract.

Our previous work examining the distribution of leptin in adult mice of both sexes after intravenous administration found that 60 mins after administration only 0.12 % of the dose was found intact in the brain, whereas the gut was a major target for leptin with 13 % of the administered leptin recovered from the stomach, small and large intestine tissues and contents in a form with potential signalling capacity. To determine if there is a reciprocal balance of leptin leaving the gut and entering circulation, iodinated leptin was administered by oral gavage to lightly anesthetised male mice. Animals were sacrificed at 30, 45, 60, 90 and 120 minutes, blood was collected and tissues dissected out. Tissues and blood were measured for trichloroacetic acid precipitable counts.

At 30 mins 53 % of the dose was detectable in the stomach, declining to 24 % by 120 mins. A peak appeared to move aborally through the small intestine, leaving the stomach less than 30 min after administration and accumulated in the cecum and large intestine by 120 min. Radioactivity was almost undetectable in systemic circulation at all time points.

These data support the hypothesis that the gut may be a major target for leptin and imply a novel route for leptin elimination via the faeces. The results also demonstrate that of the leptin that originates in or enters the gut, an almost negligible amount reaches the peripheral circulation from the gut. This together with the abundance of its receptors in the gut indicates that leptin has a major role in the digestive tract.

Nothing to Disclose: RAH, JRM

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