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 journalArticle

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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 languageEnglish (US)
Pages (from-to)947-953
Number of pages7
JournalNature Immunology
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2012

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Lymphotoxin-alpha
Obesity
Diet
Microbiota
Weight Gain
Bacteria
Interleukin-23
Mucosal Immunity
Thinness
Immunity
Transplantation
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Upadhyay, V., Poroyko, V., Kim, T. J., Devkota, S., Fu, S., Liu, D., ... Fu, Y. X. (2012). Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nature Immunology, 13(10), 947-953. https://doi.org/10.1038/ni.2403

Lymphotoxin regulates commensal responses to enable diet-induced obesity. / Upadhyay, Vaibhav; Poroyko, Valeriy; Kim, Tae Jin; Devkota, Suzanne; Fu, Sherry; Liu, Donald; Tumanov, Alexei V.; Koroleva, Ekaterina P.; Deng, Liufu; Nagler, Cathryn; Chang, Eugene B.; Tang, Hong; Fu, Yang Xin.

In: Nature Immunology, Vol. 13, No. 10, 01.10.2012, p. 947-953.

Research output: Contribution to journalArticle

Upadhyay, V, Poroyko, V, Kim, TJ, Devkota, S, Fu, S, Liu, D, Tumanov, AV, Koroleva, EP, Deng, L, Nagler, C, Chang, EB, Tang, H & Fu, YX 2012, 'Lymphotoxin regulates commensal responses to enable diet-induced obesity', Nature Immunology, vol. 13, no. 10, pp. 947-953. https://doi.org/10.1038/ni.2403
Upadhyay V, Poroyko V, Kim TJ, Devkota S, Fu S, Liu D et al. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nature Immunology. 2012 Oct 1;13(10):947-953. https://doi.org/10.1038/ni.2403
Upadhyay, Vaibhav ; Poroyko, Valeriy ; Kim, Tae Jin ; Devkota, Suzanne ; Fu, Sherry ; Liu, Donald ; Tumanov, Alexei V. ; Koroleva, Ekaterina P. ; Deng, Liufu ; Nagler, Cathryn ; Chang, Eugene B. ; Tang, Hong ; Fu, Yang Xin. / Lymphotoxin regulates commensal responses to enable diet-induced obesity. In: Nature Immunology. 2012 ; Vol. 13, No. 10. pp. 947-953.
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