Role of Leptin and SOCS3 in Inhibiting the Type I Interferon Response During Obesity
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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.
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