Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription

Kuroda, Masashi; Nishiguchi, Misa; Ugawa, Naho; Ishikawa, Etsuko; Yasuyo, Kawabata; Okamoto, Susumu; Sasaki, Waka; Miyatake, Yumiko; Sebe, Mayu; Masumoto, Shuji; Tsutsumi, Rie; Harada, Nagakatsu; Sakaue, Hiroshi

doi:10.1371/journal.pone.0233390

Cited by 16 publications

(13 citation statements)

References 40 publications

(46 reference statements)

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“…KDs that were more highly ranked for XXM but still statistically significant in XXF included genes involved in extracellular matrix organization ( Prxx2 , Mfap2 , Col1a2 , and Gas7 ), and those specific to XXF are relevant to lipid synthesis/metabolism ( Tbxas1 , Pla1a ) and immune function ( Emr1 and Ccdc109b ). Irf7 is the only KD for XYM, which has been recently suggested to be a TF in adipocytes with roles in adipose tissue immunity as well as obesity (Kuroda et al 2020).…”

Section: Resultsmentioning

confidence: 99%

Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation

Blencowe

Itoh

Chen

et al. 2021

Preprint

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Sex differences in physiology and disease in mammals result from the effects of three classes of factors that are inherently unequal in males and females: reversible (activational) effects of gonadal hormones, permanent (organizational) effects of gonadal hormones, and cell-autonomous effects of sex chromosomes, as well as genes driven by these classes of factors. Often, these factors act together to cause sex differences in specific phenotypes, but the relative contribution of each and the interactions among them remain unclear. Here, we used the Four Core Genotypes (FCG) mouse model with or without hormone replacement to distinguish the effects of each class of sex-biasing factors on transcriptome regulation in liver and adipose tissues. We found that the activational hormone levels have the strongest influence on gene expression, followed by the organizational gonadal sex effect and, lastly, sex chromosomal effect, along with interactions among the three factors. Tissue specificity was prominent, with a major impact of estradiol on adipose tissue gene regulation, and of testosterone on the liver transcriptome. The networks affected by the three sex-biasing factors include development, immunity and metabolism, and tissue-specific regulators were identified for these networks. Furthermore, the genes affected by individual sex-biasing factors and interactions among factors are associated with human disease traits such as coronary artery disease, diabetes, and inflammatory bowel disease. Our study offers a tissue-specific account of the individual and interactive contributions of major sex-biasing factors to gene regulation that have broad impact on systemic metabolic, endocrine, and immune functions.

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Section: Resultsmentioning

confidence: 99%

Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation

Blencowe

Itoh

Chen

et al. 2021

Preprint

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“…Obese asthmatic adults have increased sputum expression of NLRP3 , 74,75 while murine models of obesity‐related asthma have shown NLRP3 inflammasome‐dependent airway inflammation and hyperreactivity 76,77 . IRF7, the predicted upstream regulator of 12 out of 29 DEGs, is involved in adipocyte hypertrophy, 78 metabolic abnormalities, 79 and susceptibility to influenza 80 . IRF7 is also down‐regulated in influenza‐infected mice fed a high‐fat diet, compared with their low‐fat counterparts 81 …”

Section: Discussionmentioning

confidence: 99%

Differential gene expression in nasal airway epithelium from overweight or obese youth with asthma

Forno

Acosta‐Pérez

et al. 2022

Pediatric Allergy Immunology

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Background The mechanisms underlying the known link between overweight/obesity and childhood asthma are unclear. We aimed to identify differentially expressed genes and pathways associated with obesity‐related asthma through a transcriptomic analysis of nasal airway epithelium. Methods We compared the whole transcriptome in nasal airway epithelium of youth with overweight or obesity and asthma with that of youth of normal weight and asthma, using RNA sequencing data from a cohort of 235 Puerto Ricans aged 9–20 years (EVA‐PR) and an independent cohort of 66 children aged 6–16 years in Pittsburgh (VDKA). Differential expression analysis adjusting for age, sex, sequencing plate number, and sample sorting protocol, and the first five principal components were performed independently in each cohort. Results from the two cohorts were combined in a transcriptome‐wide meta‐analysis. Gene enrichment and network analyses were performed on top genes. Results In the meta‐analysis, 29 genes were associated with obesity‐related asthma at an FDR‐adjusted p <.05, including pro‐inflammatory genes known to be differentially expressed in adipose tissue of obese subjects (e.g., CXCL11, CXCL10, and CXCL9) and several novel genes. Functional enrichment analyses showed that pathways for interferon signaling, and innate and adaptive immune responses were down‐regulated in overweight/obese youth with asthma, while pathways related to ciliary structure or function were up‐regulated. Upstream regulatory analysis predicted significant inhibition of the IRF7 pathway. Network analyses identified “hub” genes like GBP5 and SOCS1. Conclusion Our transcriptome‐wide analysis of nasal airway epithelium identified biologically plausible genes and pathways for obesity‐related asthma in youth.

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“…In this regard, it has been shown that deficiency of IRF7, a master regulator of IFN-I induction, prevents high fat diet (HFD)-induced obesity and insulin resistance pointing to the involvement of this factor in diet-induced alterations in energy metabolism and insulin sensitivity [ 81 ]. More recently, the involvement of IRF7 in the pathogenesis of obesity was related to its capacity to regulate CCL2 expression [ 82 ]. On the same line, evidence has also been achieved on the involvement of IRF5 in obesity-associated events such as fat accumulation, insulin resistance and polarization of macrophages toward an M1 proinflammatory phenotype [ 91 ].…”

Section: The Interplay Between Type I Interferon and Obesitymentioning

confidence: 99%

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

Gessani

Belardelli

2021

Cancers

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Type I interferons (IFN-I) are antiviral cytokines endowed with multiple biological actions, including antitumor activity. Studies in mouse models and cancer patients support the concept that endogenous IFN-I play important roles in the control of tumor development and growth as well as in response to several chemotherapy/radiotherapy treatments. While IFN-I signatures in the tumor microenvironment are often considered as biomarkers for a good prognostic response to antitumor therapies, prolonged IFN-I signaling can lead to immune dysfunction, thereby promoting pathogen or tumor persistence, thus revealing the “Janus face” of these cytokines in cancer control, likely depending on timing, tissue microenvironment and cumulative levels of IFN-I signals. Likewise, IFN-I exhibit different and even opposite effects on obesity, a pathologic condition linked to cancer development and growth. As an example, evidence obtained in mouse models shows that localized expression of IFN-I in the adipose tissue results in inhibition of diet–induced obesity, while hyper-production of these cytokines by specialized cells such as plasmacytoid dendritic cells in the same tissue, can induce systemic inflammatory responses leading to obesity. Further studies in mouse models and humans should reveal the mechanisms by which IFN-I can regulate both tumor growth and obesity and to understand the role of factors such as genetic background, diet and microbioma in shaping the production and action of these cytokines under physiological and pathological conditions.

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Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription

Cited by 16 publications

References 40 publications

Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation

Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation

Differential gene expression in nasal airway epithelium from overweight or obese youth with asthma

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

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