Interleukin-1 in obesity-related low-grade inflammation: From molecular mechanisms to therapeutic strategies

Ghanbari, Mohammad Meraj; Maragheh, Salar Momen; Aghazadeh, Aida; Mehrjuyan, Seyed Reza; Hussen, Bashdar Mahmud; Baradaran, Behzad; Dastmalchi, Narges; Safaralizadeh, Reza

doi:10.1016/j.intimp.2021.107765

Cited by 51 publications

(43 citation statements)

References 157 publications

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“…It has been proposed that circulating concentrations of IL-1RA are increased in patients with obesity to counteract the obesity-associated activation of the IL-1 axis, 17 , 18 , 34 , 35 in agreement with the findings of the present study. Patients with obesity exhibited a 2.4-fold increase in serum IL-1RA concentrations as compared to NW individuals.…”

Section: Discussionsupporting

confidence: 93%

“… 15 , 16 Levels of IL-1RA are also increased in murine models and patients with obesity. 17 , 18 Mice lacking Il1rn exhibit a lean phenotype and fatty liver, accompanied by marked lipid alterations and increased atherosclerosis. 19–21 Expression and secretion of IL-1RA has also been described in adipose tissue from mice and humans, 22 , 23 being its expression strongly induced by LPS, IL-1α and IL-1β, and interferon (IFN)-β.…”

Section: Introductionmentioning

confidence: 99%

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Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity

Frühbeck¹,

Ramírez²,

Valentí³

et al. 2022

JIR

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Background Excess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels. Methods Serum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB). Results Serum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OB-IGT&T2D group (NW 440 ± 316, OB-NG 899 ± 562, OB-IGT&T2D 1265 ± 739 pg/mL; P <0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68 , and MMP9 . Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 ± 1009 to 660 ± 538 pg/mL ( P <0.001). Conclusion Serum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity

Frühbeck¹,

Ramírez²,

Valentí³

et al. 2022

JIR

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“…Interestingly, the levels of circulating pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IL-1β) are normal or even low in IL-1RA knockout mice, indicating that inflammatory changes in response to a HFD are unlikely to be responsible for the lean phenotype. Nonetheless, recombinant IL-1RA (Anakinra) has been found to be beneficial in animal models ( 284 ) of diabetes and patients with diabetes ( 285 ), suggesting that excess IL-1 signaling contributes to beta cell damage in diabetes ( 286 ). Further studies are required to evaluate whether targeting IL-1RA in AT could offer therapeutic benefits in patients with obesity.…”

Section: Adipokinesmentioning

confidence: 99%

Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation

et al. 2022

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Chronic low-grade inflammation in adipose tissue (AT) is a hallmark of obesity and contributes to various metabolic disorders, such as type 2 diabetes and cardiovascular diseases. Inflammation in ATs is characterized by macrophage infiltration and the activation of inflammatory pathways mediated by NF-κB, JNK, and NLRP3 inflammasomes. Adipokines, hepatokines and myokines — proteins secreted from AT, the liver and skeletal muscle play regulatory roles in AT inflammation via endocrine, paracrine, and autocrine pathways. For example, obesity is associated with elevated levels of pro-inflammatory adipokines (e.g., leptin, resistin, chemerin, progranulin, RBP4, WISP1, FABP4, PAI-1, Follistatin-like1, MCP-1, SPARC, SPARCL1, and SAA) and reduced levels of anti-inflammatory adipokines such as adiponectin, omentin, ZAG, SFRP5, CTRP3, vaspin, and IL-10. Moreover, some hepatokines (Fetuin A, DPP4, FGF21, GDF15, and MANF) and myokines (irisin, IL-6, and DEL-1) also play pro- or anti-inflammatory roles in AT inflammation. This review aims to provide an updated understanding of these organokines and their role in AT inflammation and related metabolic abnormalities. It serves to highlight the molecular mechanisms underlying the effects of these organokines and their clinical significance. Insights into the roles and mechanisms of these organokines could provide novel and potential therapeutic targets for obesity-induced inflammation.

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“…We used bioinformatic analysis to investigate the roles DE circRNAs active in a ceRNA network to regulate genes associated with chronic in ammation by regulating IL-1, IL-6, and TNF-alpha [31,32] .…”

Section: Validation Of Obesity-related Ncrnas In the Cerna Networkmentioning

confidence: 99%

Transcriptome of visceral adipose tissue identifies an inflammation-related ceRNA network that regulates obesity

Zhang

Cao

et al. 2022

Mol Cell Biochem

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Obesity is becoming an epidemic of widespread concern, but the underlying causes remain elusive. In this study, whole transcriptome RNA sequencing (RNA-seq) revealed differential pro les of noncoding (nc) RNAs and mRNAs in visceral adipose tissue (VAT) from obese (BMI >32.5 kg/m 2 ) and lean (BMI < 20 kg/m 2 ) individuals, with 1920 differentially expressed (DE) genes, 1466 long noncoding (lnc)RNAs, 122 micro (mi)RNAs, and 52 circular (circ)RNAs identi ed. Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis revealed that these ncRNAs were involved in in ammation-related pathways that included cytokine-cytokine receptor interaction, the tumor necrosis factor and nuclear factor kappa B signaling pathways. The results indicated a critical role of in ammation in the pathogenesis of obesity. The network interaction of lncRNA, circRNA, and miRNA revealed a competing endogenous (ce)RNA network that was associated with in ammation. The ceRNA network included circORC5/miR-197-5p/TNFRSF10D and circNTRK2/miR-760/LAT, which were dysregulated in obese patients. Notably, the overexpression of TNFRSF10D and LAT were signi cantly positively associated with body weight in obese patients. In conclusion, this whole transcriptome study provided a pool of data that will be useful for identifying biomarkers of obesity and identi ed an obesityassociated ceRNA network that is regulated by circORC5 and circNTRK2.

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Interleukin-1 in obesity-related low-grade inflammation: From molecular mechanisms to therapeutic strategies

Cited by 51 publications

References 157 publications

Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity

Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity

Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation

Transcriptome of visceral adipose tissue identifies an inflammation-related ceRNA network that regulates obesity

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