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.
authors.affiliation: Department of Pathology and Committee on Immunology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Upadhyay
authors.forename: Valeriy
authors.initials: V
authors.lastname: Poroyko
authors.forename: Tae-jin
authors.initials: TJ
authors.lastname: Kim
authors.forename: Suzanne
authors.initials: S
authors.lastname: Devkota
authors.forename: Sherry
authors.initials: S
authors.lastname: Fu
authors.forename: Donald
authors.initials: D
authors.lastname: Liu
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tumanov
authors.forename: Ekaterina P
authors.initials: EP
authors.lastname: Koroleva
authors.forename: Liufu
authors.initials: L
authors.lastname: Deng
authors.forename: Cathryn
authors.initials: C
authors.lastname: Nagler
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development / Q000276:immunology; D002432:Cecum / Q000382:microbiology / Q000637:transplantation; D004032:Diet; D004734:Energy Metabolism; D005856:Germ-Free Life; D018928:Immunity, Mucosal; D053759:Interleukin-23 / Q000172:deficiency / Q000502:physiology; D007378:Interleukins / Q000172:deficiency / Q000502:physiology; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054892:Metagenome; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D015430:Weight Gain / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D053759:Interleukin-23; D007378:Interleukins; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D000097043:Interleukin-22; C505699:Ltbr protein, mouse