Lymphotoxin regulates commensal responses to enable diet-induced obesity

Vaibhav Upadhyay; Valeriy Poroyko; Tae Jin Kim; Suzanne Devkota; Sherry Fu; Donald Liu; Alexei V. Tumanov; Ekaterina P. Koroleva; Liufu Deng; Cathryn Nagler; Eugene B. Chang; Hong Tang; Yang Xin Fu

doi:10.1038/ni.2403

Lymphotoxin regulates commensal responses to enable diet-induced obesity

Vaibhav Upadhyay
, Valeriy Poroyko
, Tae Jin Kim
, Suzanne Devkota
, Sherry Fu
, Donald Liu
, Alexei V. Tumanov
, Ekaterina P. Koroleva
, Liufu Deng
, Cathryn Nagler
, Eugene B. Chang
, Hong Tang
, Yang Xin Fu

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr^-/- mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr^-/- mice with their obese siblings rescued weight gain in Ltbr^-/- mice, demonstrating the communicability of the obese phenotype. Ltbr^-/- mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.

Original language	English (US)
Pages (from-to)	947-953
Number of pages	7
Journal	Nature Immunology
Volume	13
Issue number	10
DOIs	https://doi.org/10.1038/ni.2403
State	Published - Oct 2012
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni.2403

Cite this

@article{b23a14fab37b409da452d8e95518b9dc,

title = "Lymphotoxin regulates commensal responses to enable diet-induced obesity",

abstract = "Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr-/- mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr-/- mice with their obese siblings rescued weight gain in Ltbr-/- mice, demonstrating the communicability of the obese phenotype. Ltbr-/- mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.",

author = "Vaibhav Upadhyay and Valeriy Poroyko and Kim, \{Tae Jin\} and Suzanne Devkota and Sherry Fu and Donald Liu and Tumanov, \{Alexei V.\} and Koroleva, \{Ekaterina P.\} and Liufu Deng and Cathryn Nagler and Chang, \{Eugene B.\} and Hong Tang and Fu, \{Yang Xin\}",

note = "Funding Information: This manuscript is dedicated to the memory of Dr. Donald Liu, who provided critical efforts and support. We thank B. Becher (University of Zurich) for IL-23-Ig, C. Dong (MD Anderson Cancer Center) for IL-17, O. Wenjun (Genentech) for IL-22. V.U. was supported by the American Heart Association (AHA Predoctoral 11PRE7320015) and the US National Institutes of Health Medical Scientist Training Program grant GM007281 to the University of Chicago Pritzker School of Medicine. This research was supported by pilot grants from Digestive Diseases Research Core Center (p30 DK42086), the University of Chicago Institutional Translational Medicine (UL1 RR024999), and US National Institutes of Health grants, AI090392, DK080736 and CA134563 to Y.-X.F. T.J.K. was partially funded by the Korea Foundation for International Cooperation of Science \& Technology (KICOS) grant (K20702001994-11A0500-03610).",

year = "2012",

month = oct,

doi = "10.1038/ni.2403",

language = "English (US)",

volume = "13",

pages = "947--953",

journal = "Nature Immunology",

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T1 - Lymphotoxin regulates commensal responses to enable diet-induced obesity

AU - Upadhyay, Vaibhav

AU - Poroyko, Valeriy

AU - Kim, Tae Jin

AU - Devkota, Suzanne

AU - Fu, Sherry

AU - Liu, Donald

AU - Tumanov, Alexei V.

AU - Koroleva, Ekaterina P.

AU - Deng, Liufu

AU - Nagler, Cathryn

AU - Chang, Eugene B.

AU - Tang, Hong

AU - Fu, Yang Xin

N1 - Funding Information: This manuscript is dedicated to the memory of Dr. Donald Liu, who provided critical efforts and support. We thank B. Becher (University of Zurich) for IL-23-Ig, C. Dong (MD Anderson Cancer Center) for IL-17, O. Wenjun (Genentech) for IL-22. V.U. was supported by the American Heart Association (AHA Predoctoral 11PRE7320015) and the US National Institutes of Health Medical Scientist Training Program grant GM007281 to the University of Chicago Pritzker School of Medicine. This research was supported by pilot grants from Digestive Diseases Research Core Center (p30 DK42086), the University of Chicago Institutional Translational Medicine (UL1 RR024999), and US National Institutes of Health grants, AI090392, DK080736 and CA134563 to Y.-X.F. T.J.K. was partially funded by the Korea Foundation for International Cooperation of Science & Technology (KICOS) grant (K20702001994-11A0500-03610).

PY - 2012/10

Y1 - 2012/10

N2 - Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr-/- mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr-/- mice with their obese siblings rescued weight gain in Ltbr-/- mice, demonstrating the communicability of the obese phenotype. Ltbr-/- mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.

AB - Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr-/- mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr-/- mice with their obese siblings rescued weight gain in Ltbr-/- mice, demonstrating the communicability of the obese phenotype. Ltbr-/- mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.

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JO - Nature Immunology

JF - Nature Immunology

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Lymphotoxin regulates commensal responses to enable diet-induced obesity

Abstract

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