Role of Leptin and SOCS3 in Inhibiting the Type I Interferon Response During Obesity
- 390 Downloads
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.
KEY WORDSobesity leptin SOCS3 type I interferon toll-like receptor
This study was partially supported by the FONDO SECTORIAL SALUD-CONACYT grant no. 127013. We thank Monica Resendiz for her technical assistance. We thank the volunteers for their participation.
- 15.Yang Y, Sun H, Mo X, Liu Y, Jia H, Li X, et al. Prediction of novel genes associated with negative regulators of toll-like receptors-induced inflammation based on endotoxin tolerance. Inflammation. 2012:1–11Google Scholar
- 17.Walsh, M., J. Jonsson, M.M. Richardson, G. Lipka, D. Purdie, A. Clouston, et al. 2006. Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1. Gut 55: 529.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Ueki, K., T. Kondo, and C.R. Kahn. 2004. Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Molecular and Cellular Biology 24: 5434–46.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Terán-Cabanillas E, Montalvo-Corral M, Silva-Campa E, Caire-Juvera G, Moya-Camarena SY, Hernández J. Production of interferon α and β, pro-inflammatory cytokines and the expression of suppressor of cytokine signaling (SOCS) in obese subjects infected with influenza A/H1N1. Clinical nutrition (Edinburgh, Scotland). 2014;33:922–6.Google Scholar
- 26.Michaud, F., F. Coulombe, E. Gaudreault, C. Paquet-Bouchard, M. Rola-Pleszczynski, and J. Gosselin. 2010. Epstein-Barr virus interferes with the amplification of IFNalpha secretion by activating suppressor of cytokine signaling 3 in primary human monocytes. PloS One 5: e11908.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Papathanassoglou, E., K. El-Haschimi, X.C. Li, G. Matarese, T. Strom, and C. Mantzoros. 2006. Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. The Journal of Immunology 176: 7745–52.CrossRefPubMedGoogle Scholar
- 31.Jaedicke, K.M., A. Roythorne, K. Padget, S. Todryk, P.M. Preshaw, and J.J. Taylor. 2013. Leptin up-regulates TLR2 in human monocytes. Journal of Leukocyte Biology.Google Scholar