title: Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice.
abstract: The importance of B-isoform of leptin receptor (LEPR-B) signaling in the hypothalamus, pancreas, or liver has been well characterized, but in the intestine, a unique site of entry for dietary nutrition into the body, it has been relatively ignored. To address this question, we characterized a mouse model deficient for LEPR-B specifically in intestinal epithelial cells (IECs). (IEC)LEPR-B-knockout (KO) and wild-type (WT) mice were generated by Cre-Lox strategy and fed a normal or high-fat diet (HFD). The analyses of the animals involved histology and immunohistochemistry of intestinal mucosa, indirect calorimetric measurements, whole-body composition, and expression and activities of nutrient transporters. (IEC)LEPR-B-KO mice exhibited a 2-fold increase in length of jejunal villi and have normal growth on a normal diet but were less susceptible (P<0.01) to HFD-induced obesity. No differences occurred in energy intake and expenditure between (IEC)LEPR-B-WT and -KO mice, but (IEC)LEPR-B-KO mice fed an HFD showed increased excreted fats (P<0.05). Activities of the Na(+)/glucose cotransporter SGLT-1 and GLUT2 were unaffected in LEPR-B-KO jejunum, while GLUT5-mediated fructose transport and PepT1-mediated peptide transport were substantially reduced (P<0.01). These data demonstrate that intestinal LEPR-B signaling is important for the onset of diet-induced obesity. They suggest that intestinal LEPR-B could be a potential per os target for prevention against obesity.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Annabelle
authors.initials: A
authors.lastname: Tavernier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Cavin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Maude
authors.initials: M
authors.lastname: Le Gall
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Robert
authors.initials: R
authors.lastname: Ducroc
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8251, Paris, France;
authors.forename: Raphaël G P
authors.initials: RG
authors.lastname: Denis
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Françoise
authors.initials: F
authors.lastname: Cluzeaud
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Sandra
authors.initials: S
authors.lastname: Guilmeau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France;
authors.forename: Yassine
authors.initials: Y
authors.lastname: Sakar
authors.affiliation: Service de Coprologie Fonctionnelle, Hopital La Pitié Salpêtrière, Paris, France;
authors.forename: Laurence
authors.initials: L
authors.lastname: Barbot
authors.affiliation: Service de Coprologie Fonctionnelle, Hopital La Pitié Salpêtrière, Paris, France;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kapel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France; Université Pierre et Marie Curie, Paris, France;
authors.forename: Johanne
authors.initials: J
authors.lastname: Le Beyec
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France; Service de Gastroenterologie et d'Assistance Nutritive, Hopital Beaujon, Clichy, France; and.
authors.forename: Francisca
authors.initials: F
authors.lastname: Joly
authors.affiliation: Department of Medicine and Neuroscience, Albert Einstein College of Medicine, New York, New York, USA.
authors.forename: Streamson
authors.initials: S
authors.lastname: Chua
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8251, Paris, France;
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1149, Unité de Formation et de Recherche (UFR) de Médecine Paris Diderot, Sorbonne Paris Cite, Paris, France; andre.bado@inserm.fr.
authors.forename: Andre
authors.initials: A
authors.lastname: Bado
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001823:Body Composition; D001835:Body Weight; D049109:Cell Proliferation; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D002149:Energy Intake; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism*; D051296:Glucose Transporter Type 5; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology*; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D020738:Leptin; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; D054411:Receptors, Leptin; C489941:Slc15a1 protein, mouse; C495682:Slc2a2 protein, mouse; C465351:Slc2a5 protein, mouse; D027981:Symporters; C515447:leptin receptor, mouse
keywords: absorption; energy expenditure; gut mucosa; high-fat diet; hypothalamic neuropeptides