Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells
| Autor: | V Descatoire, T Aparicio, Muriel Hourseau, J-P Marmuse, A-L Pelletier, Francisca Joly, K. Arapis, Françoise Cluzeaud, Robert Ducroc, J Le Beyec, Anne Couvelard, M. Le Gall, André Bado |
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| Rok vydání: | 2014 |
| Předmět: |
Leptin
Male endocrine system medicine.medical_specialty Duodenum Endocrinology Diabetes and Metabolism Radioimmunoassay Fluorescent Antibody Technique Mice Obese Medicine (miscellaneous) Tryptophan Hydroxylase Diet High-Fat Real-Time Polymerase Chain Reaction digestive system Mice chemistry.chemical_compound Downregulation and upregulation Internal medicine Adipocyte Adipocytes Enterochromaffin Cells medicine Animals Humans Paired Box Transcription Factors Obesity 5-HT receptor Homeodomain Proteins Nutrition and Dietetics Leptin receptor Stomach digestive oral and skin physiology Up-Regulation Mice Inbred C57BL Endocrinology Real-time polymerase chain reaction chemistry Gastric Mucosa Enterochromaffin cell Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | International Journal of Obesity. 38:1357-1364 |
| ISSN: | 1476-5497 0307-0565 |
| DOI: | 10.1038/ijo.2014.14 |
| Popis: | In obesity, while hyperleptinemia highly correlates with excess fat mass, the status of gastric leptin remains unknown. Here, we investigated the expression of leptin in stomach biopsies of obese humans and analyzed the temporal changes of gastric leptin expression in response to diet-induced obesity and its impact on 5-hydroxytryptamine (5HT)-producing cells.Enterochromaffin (EC) cells and expression of leptin, PAX4 (critical factor for EC specification), tryptophane hydroxylase-1 (TPH1, the peripheral rate-limiting enzyme for 5HT) and 5HT were examined by immunofluorescence, quantitative real-time PCR, radioimmunoassay, respectively, in stomach and duodenum biopsies from 19 obese and 14 normo-weighed individuals, and in mucosa scrapings from C57Bl6/J diet-induced obese mice, leptin-deficient ob/ob mice and intestine-specific leptin receptor isoform B-deficient mice.Gastric mucosa of obese subjects displays an increased expression of leptin (LEP mRNA by fivefold and protein by twofold, P0.01), TPH1 ((1.75-2.73, 95% confidence interval (CI)) vs (0.38-0.67, 95% CI); P0.01) and PAX4 ((1.33-2.11, 95%CI) vs (0.62-0.81, 95% CI); P0.01) as compared with normo-weighed individuals. In diet-induced obese mice, the overexpressions of gastric leptin, antral Pax4, Tph1 and increased EC cell number occurred before the onset of obesity and hyperleptinemia (reflect of adipocyte leptin production). In addition, leptin deficiency was associated with reduced Pax4 mRNA, whereas oral leptin treatment enhanced both Tph1 and Pax4 mRNA. Finally, mice with an intestine-specific deletion of leptin signaling exhibit significant decrease in duodenal mucosa 5HT content.These data demonstrate that gastric leptin is upregulated in obese individuals. RESULTS from high-fat diet mice showed that overexpression of gastric leptin that is linked to gut '5HT pathway' occurred before the onset of obesity and expansion of fat mass. This may be relevant in the pathophysiology of obesity. |
| Databáze: | OpenAIRE |
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