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J Interferon Cytokine Res ; 43(7): 287-298, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37428556

RESUMEN

Diet-induced obesity triggers elevation of circulating pro-inflammatory cytokines and acute-phase proteins, including interferons (IFNs). IFNs strongly contribute to low-grade inflammation associated with obesity-related complications, such as nonalcoholic fat liver disease and diabetes. In this study, AG129 mice model (double-knockout strain for IFN α/ß/γ receptors) was fed with a high-fat high-sucrose (HFHS) diet (Western diet) for 20 weeks aiming to understand the impact of IFN receptor ablation on diet-induced obesity, insulin resistance, and nonalcoholic fat liver disease. Mice were responsive to the diet, becoming obese after 20 weeks of HFHS diet which was accompanied by 2-fold increase of white adipose tissues. Moreover, animals developed glucose and insulin intolerance, as well as dysregulation of insulin signaling mediators such as Insulin Receptor Substrate 1 (IRS1), protein kinase B (AKT), and S6 ribosomal protein. Liver increased interstitial cells, and lipid accumulation was also found, presenting augmented fibrotic markers (transforming growth factor beta 1 [Tgfb1], Keratin 18 [Krt18], Vimentin [Vim]), yet lower expression on IFN receptor downstream proteins (Toll-like receptor [TLR] 4, nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB], and cAMP response element-binding protein [CREB]). Thus, IFN receptor ablation promoted effects on NFκB and CREB pathways, with no positive effects on systemic homeostasis in diet-induced obese mice. Therefore, we conclude that IFN receptor signaling is not essential for promoting the complications of diet-induced obesity and thus cannot be correlated with metabolic diseases in a noninfectious condition.


Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Resistencia a la Insulina/fisiología , Dieta Occidental , Obesidad/complicaciones , Hígado/metabolismo , Insulina/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Dieta Alta en Grasa/efectos adversos , Receptores de Interferón/metabolismo , Ratones Endogámicos C57BL
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