Positive regulatory control loop between gut leptin and intestinal GLUT2/GLUT5 transporters links to hepatic metabolic functions in rodents
| Autor: | Mathilde Avenati, Robert Ducroc, André Bado, Corinne Nazaret, Yassine Sakar, Amal Ait Omar, Benoit Viollet, Philippe Lettéron |
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| Přispěvatelé: | Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), This work was supported by the INSERM (Institut National de la Sante´ et de la Recherche Me´ dicale), the UFR of Medicine of University Paris 7 Denis Diderot, and by a grant (to YS ) of Socie´te´ Francophone de Nutrition Clinique et Metabolisme (SFNEP-Antadir Federation), a grant (to RD) of Association pour l'Etude du Diabete et des Maladies Metaboliques (ALFEDIAM-Becton Dickinson), and a grant (to AB) of Institut Benjamin Delessert., Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Unknown, User, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Blood Glucose
Leptin Male medicine.medical_specialty Glucose Transport Proteins Facilitative lcsh:Medicine Fructose Gastroenterology and Hepatology/Small Intestine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Nutrition/Obesity Internal medicine Adipocyte medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Homeostasis Glucose homeostasis Gastroenterology and Hepatology/Stomach and Duodenum [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Rats Wistar lcsh:Science 030304 developmental biology Glucose Transporter Type 2 0303 health sciences Multidisciplinary biology Glucose Transporter Type 5 lcsh:R digestive oral and skin physiology Gluconeogenesis Fructose transport Rats Mice Inbred C57BL Endocrinology Liver chemistry Physiology/Gastroenterology and Hepatology Galactose biology.protein GLUT2 lcsh:Q GLUT5 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2009, 4 (11), pp.e7935. 〈10.1371/journal.pone.0007935〉 PLoS ONE, Public Library of Science, 2009, 4 (11), pp.e7935. ⟨10.1371/journal.pone.0007935⟩ PLoS ONE, Vol 4, Iss 11, p e7935 (2009) PLoS ONE, 2009, 4 (11), pp.e7935. ⟨10.1371/journal.pone.0007935⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0007935〉 |
| Popis: | International audience; BACKGROUND AND AIMS: The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. METHODOLOGY: Wistar rats, wild type and AMPKalpha(2) (-/-) mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. PRINCIPAL FINDINGS: First, in vitro luminal leptin activating its receptors coupled to PKCbetaII and AMPKalpha, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. CONCLUSION/SIGNIFICANCE: These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious. |
| Databáze: | OpenAIRE |
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