{"title":"干扰素受体α/β/γ消融在AG129小鼠屈曲模型中西方饮食诱导的肥胖和胰岛素抵抗中的作用","authors":"Emylle Costa-Bartuli, Adrielle Tenório Rodrigues, Sofia Andrade Ribeiro Bastos, Nathan Kistenmacker, Leticia Crepaldi, Christina Maeda Takiya, Patricia Zancan, Fabio Mendonça Gomes, Mauro Sola-Penna","doi":"10.1089/jir.2023.0047","DOIUrl":null,"url":null,"abstract":"<p><p>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/β/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.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Role of Interferon Receptors α/β/γ Ablation During Western Diet-Induced Obesity and Insulin Resistance in the Inflectional Model AG129 Mice Strain.\",\"authors\":\"Emylle Costa-Bartuli, Adrielle Tenório Rodrigues, Sofia Andrade Ribeiro Bastos, Nathan Kistenmacker, Leticia Crepaldi, Christina Maeda Takiya, Patricia Zancan, Fabio Mendonça Gomes, Mauro Sola-Penna\",\"doi\":\"10.1089/jir.2023.0047\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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/β/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.</p>\",\"PeriodicalId\":16261,\"journal\":{\"name\":\"Journal of Interferon and Cytokine Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Interferon and Cytokine Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/jir.2023.0047\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Interferon and Cytokine Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jir.2023.0047","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The Role of Interferon Receptors α/β/γ Ablation During Western Diet-Induced Obesity and Insulin Resistance in the Inflectional Model AG129 Mice Strain.
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/β/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.
期刊介绍:
Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.