title: Role of Leptin and SOCS3 in Inhibiting the Type I Interferon Response During Obesity.
abstract: Obesity provokes an imbalance in the immune system, including an aberrant type I interferon response during some viral infections and after TLR stimulation. SOCS3 overexpression and altered systemic leptin levels could be responsible for the reduced type I interferon production in people with obesity and, eventually, significantly increase the risk of viral infection. The aim of this study was to determine whether SOCS3- and leptin-induced tolerance are responsible for the reduced type I interferon production in people with obesity. SOCS3 overexpression in PBMCs from people with obesity was inhibited with the small interfering RNA (siRNA) assay, and leptin-induced tolerance was evaluated in PBMCs from non-obese volunte\ers and U937 cells treated with TLR ligands. SOCS3, but not SOCS1, gene silencing via siRNA increased the type I interferon response in PBMCs obtained from people with obesity. On the other hand, leptin induced SOCS3 expression and inhibited type I interferons in PBMCs from healthy donors and in U937 monocytes stimulated with TLR ligands. Taken together, these results demonstrate that reduced type I interferon production in obesity is caused by SOCS3 overexpression as well as tolerance induced by leptin. Here, we demonstrate a key role of leptin and SOCS3 in inhibiting the type I interferon response during obesity.
authors.affiliation: Laboratorio de Inmuología, Coordinación de Nutrición, Centro de Investigación en Alimentación y Desarrollo, A.C., Km 0.6 Carretera a la Victoria, Hermosillo, Sonora, México, 83000.|Unidad Académica de Ciencias de la Nutrición y Gastronomía, Universidad Autónoma de Sinaloa, Sinaloa, México.
authors.forename: Elí
authors.initials: E
authors.lastname: Terán-Cabanillas
authors.affiliation: Laboratorio de Inmuología, Coordinación de Nutrición, Centro de Investigación en Alimentación y Desarrollo, A.C., Km 0.6 Carretera a la Victoria, Hermosillo, Sonora, México, 83000. jhdez@ciad.mx.
authors.forename: Jesús
authors.identifier: http://orcid.org/0000-0002-5131-3600
authors.initials: J
authors.lastname: Hernández
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D020738:Leptin / Q000502:physiology*; D008024:Ligands; D009000:Monocytes; D009765:Obesity / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000502:physiology*; D051193:Toll-Like Receptors; D020298:U937 Cells
chemical_list: D007370:Interferon Type I; D020738:Leptin; D008024:Ligands; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D051193:Toll-Like Receptors
keywords: SOCS3; leptin; obesity; toll-like receptor; type I interferon