TY - JOUR
T1 - Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice
AU - Tavernier, Annabelle
AU - Cavin, Jean Baptiste
AU - Le Gall, Maude
AU - Ducroc, Robert
AU - Denis, Raphaël G.P.
AU - Cluzeaud, Franҫoise
AU - Guilmeau, Sandra
AU - Sakar, Yassine
AU - Barbot, Laurence
AU - Kapel, Nathalie
AU - Le Beyec, Johanne
AU - Joly, Francisca
AU - Chua, Streamson
AU - Luquet, Serge
AU - Bado, Andre
N1 - Publisher Copyright:
© FASEB.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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.
AB - 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.
KW - Absorption
KW - Energy expenditure
KW - Gut mucosa
KW - High-fat diet
KW - Hypothalamic neuropeptides
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UR - http://www.scopus.com/inward/citedby.url?scp=84907200665&partnerID=8YFLogxK
U2 - 10.1096/fj.14-255158
DO - 10.1096/fj.14-255158
M3 - Article
C2 - 24928195
AN - SCOPUS:84907200665
SN - 0892-6638
VL - 28
SP - 4100
EP - 4110
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -