Dataset Information

CircARF3 Alleviates Mitophagy-Mediated Inflammation by Targeting miR-103/TRAF3 in Mouse Adipose Tissue.

ABSTRACT: Adipose inflammation is an important cause for obesity-associated metabolic disorders, including insulin resistance and hypertension. Here we investigated that a circular RNA (circRNA), which we termed circARF3 (ADP-ribosylation factor 3), acts as an endogenous miR-103 sponge to alleviate adipose inflammation by promoting mitophagy. On the other hand, miR-103 aggravated inflammation by inhibiting mitophagy, revealing that miR-103 acts as a positive regulator of adipose inflammation. Furthermore, we found that tumor necrosis factor receptor-associated factor 3 (TRAF3), as a miR-103 downstream target, mediates the functions of miR-103 in adipose inflammation. Overexpressing TRAF3 attenuated miR-103-induced inflammation by accelerating mitophagy. Moreover, we identified that circARF3 blocked miR-103 effects, which resulted in an increase in TRAF3 expression. TRAF3 restrained the nuclear factor ?B (NF-?B)-signaling pathway, heightened mitophagy, and suppressed NLRP3 inflammasome activation ultimately. Our data showed that circARF3 acts as an endogenous miR-103 sponge to inhibit mitophagy-mediated adipose inflammation both in vitro and in vivo. These findings disclose a new regulatory pathway for adipose inflammation, which consists of circARF3, miR-103, and TRAF3. This study can be a useful addition to our knowledge, as it provides a new strategy for the prevention of adipose inflammation in obesity disorder.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC6325073 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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circARF3 Alleviates Mitophagy-Mediated Inflammation by Targeting miR-103/TRAF3 in Mouse Adipose Tissue.

Zhang Zhenzhen Z Zhang Tiantian T Feng Ruonan R Huang Hongtao H Xia Tianyu T Sun Chao C

Molecular therapy. Nucleic acids 20181201

Adipose inflammation is an important cause for obesity-associated metabolic disorders, including insulin resistance and hypertension. Here we investigated that a circular RNA (circRNA), which we termed circARF3 (ADP-ribosylation factor 3), acts as an endogenous miR-103 sponge to alleviate adipose inflammation by promoting mitophagy. On the other hand, miR-103 aggravated inflammation by inhibiting mitophagy, revealing that miR-103 acts as a positive regulator of adipose inflammation. Furthermore, ...[more]

PMID: 30623853

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Project description:BackgroundObesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease.MethodsWe compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR-/-) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed.ResultsAfter 12-16 weeks, LDLR-/- mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR-/- mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20 weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR-/- mice fed HFSC or HFC.ConclusionThe use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR-/- mice. Hence LDLR-/- mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation.

Dataset Information

CircARF3 Alleviates Mitophagy-Mediated Inflammation by Targeting miR-103/TRAF3 in Mouse Adipose Tissue.

Publications

circARF3 Alleviates Mitophagy-Mediated Inflammation by Targeting miR-103/TRAF3 in Mouse Adipose Tissue.

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