Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice

Annabelle Tavernier, Jean Baptiste Cavin, Maude Le Gall, Robert Ducroc, Raphaël G.P. Denis, Franҫoise Cluzeaud, Sandra Guilmeau, Yassine Sakar, Laurence Barbot, Nathalie Kapel, Johanne Le Beyec, Francisca Joly, Streamson Chua, Serge Luquet, Andre Bado

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4100-4110
Number of pages11
JournalFASEB Journal
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2014

Keywords

  • Absorption
  • Energy expenditure
  • Gut mucosa
  • High-fat diet
  • Hypothalamic neuropeptides

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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