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, Franc¸oise Cluzeaud, Sandra Guilmeau, Yassine Sakar, Laurence Barbot, Nathalie Kapel, Johanne Le Beyec, Francisca Joly, Streamson C. Chua, Jr., Serge Luquet, Andre Bado

Research output: Contribution to journalArticle

19 Citations (Scopus)

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). IECLEPR-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. IECLEPR-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 IECLEPR-B-WT and -KO mice, but IECLEPR-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

Fingerprint

Nutrition
Leptin
Knockout Mice
Nutrients
High Fat Diet
Obesity
Food
Fats
Diet
Leptin Receptors
Jejunum
Intestinal Mucosa
Body Composition
Energy Intake
Fructose
Energy Metabolism
Hypothalamus
Intestines
Pancreas
Histology

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Tavernier, A., Cavin, J. B., Le Gall, M., Ducroc, R., Denis, R. G. P., Cluzeaud, F., ... Bado, A. (2014). Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice. FASEB Journal, 28(9), 4100-4110. https://doi.org/10.1096/fj.14-255158

Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice. / Tavernier, Annabelle; Cavin, Jean Baptiste; Le Gall, Maude; Ducroc, Robert; Denis, Raphaël G P; Cluzeaud, Franc¸oise; Guilmeau, Sandra; Sakar, Yassine; Barbot, Laurence; Kapel, Nathalie; Le Beyec, Johanne; Joly, Francisca; Chua, Jr., Streamson C.; Luquet, Serge; Bado, Andre.

In: FASEB Journal, Vol. 28, No. 9, 01.09.2014, p. 4100-4110.

Research output: Contribution to journalArticle

Tavernier, A, Cavin, JB, Le Gall, M, Ducroc, R, Denis, RGP, Cluzeaud, F, Guilmeau, S, Sakar, Y, Barbot, L, Kapel, N, Le Beyec, J, Joly, F, Chua, Jr., SC, Luquet, S & Bado, A 2014, 'Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice', FASEB Journal, vol. 28, no. 9, pp. 4100-4110. https://doi.org/10.1096/fj.14-255158
Tavernier, Annabelle ; Cavin, Jean Baptiste ; Le Gall, Maude ; Ducroc, Robert ; Denis, Raphaël G P ; Cluzeaud, Franc¸oise ; Guilmeau, Sandra ; Sakar, Yassine ; Barbot, Laurence ; Kapel, Nathalie ; Le Beyec, Johanne ; Joly, Francisca ; Chua, Jr., Streamson C. ; Luquet, Serge ; Bado, Andre. / Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice. In: FASEB Journal. 2014 ; Vol. 28, No. 9. pp. 4100-4110.
@article{978edf6fbdad480e9f2e5379cf0614a7,
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). IECLEPR-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. IECLEPR-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 IECLEPR-B-WT and -KO mice, but IECLEPR-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.",
keywords = "Absorption, Energy expenditure, Gut mucosa, High-fat diet, Hypothalamic neuropeptides",
author = "Annabelle Tavernier and Cavin, {Jean Baptiste} and {Le Gall}, Maude and Robert Ducroc and Denis, {Rapha{\"e}l G P} and Franc¸oise Cluzeaud and Sandra Guilmeau and Yassine Sakar and Laurence Barbot and Nathalie Kapel and {Le Beyec}, Johanne and Francisca Joly and {Chua, Jr.}, {Streamson C.} and Serge Luquet and Andre Bado",
year = "2014",
month = "9",
day = "1",
doi = "10.1096/fj.14-255158",
language = "English (US)",
volume = "28",
pages = "4100--4110",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "9",

}

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, Franc¸oise

AU - Guilmeau, Sandra

AU - Sakar, Yassine

AU - Barbot, Laurence

AU - Kapel, Nathalie

AU - Le Beyec, Johanne

AU - Joly, Francisca

AU - Chua, Jr., Streamson C.

AU - Luquet, Serge

AU - Bado, Andre

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). IECLEPR-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. IECLEPR-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 IECLEPR-B-WT and -KO mice, but IECLEPR-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). IECLEPR-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. IECLEPR-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 IECLEPR-B-WT and -KO mice, but IECLEPR-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

UR - http://www.scopus.com/inward/record.url?scp=84907200665&partnerID=8YFLogxK

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

VL - 28

SP - 4100

EP - 4110

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 9

ER -