microRNAs as a New Mechanism Regulating Adipose Tissue Inflammation in Obesity and as a Novel Therapeutic Strategy in the Metabolic Syndrome

Ge, Qian; Brichard, Sonia; Xu, Yifeng; Li, Qifu

doi:10.1155/2014/987285

Cited by 88 publications

(69 citation statements)

References 91 publications

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“…Obese WAT displays classical signs of chronic inflammation, a key feature of obesity. Obesity leads to a chronic inflammatory state that is initiated and exacerbated in the WAT (Ge et al, 2014; Xu et al, 2003). For example, visceral adipocytes promote systemic inflammation by secreting mediators such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and leptin, among others (Fontana et al, 2007).…”

Section: Adipose Tissue and Obesitymentioning

confidence: 99%

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity

2017

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Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatics and adipose tissue, and linking lymphatic function with metabolic diseases, obesity and adipose tissue also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatics-adipose tissue relationship.

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Section: Adipose Tissue and Obesitymentioning

confidence: 99%

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity

2017

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“…Unlike in many other species, including primates, known human miRNA coding sequences are located mostly in the introns of other genes; however, miRNAs coded in intergenic regions have been more frequently associated with human diseases (Ghorai and Ghosh 2014). Approximately 40 miRNAs have been found to influence adipogenesis (Son et al 2014) and many miRNAs contribute to the regulation of inflammation in white adipose tissue (Ge et al 2014). This group includes miR-31, which is produced by adipocytes and its expression has been found to increase after treatment by a macrophage LPS-conditioned medium, mimicking the inflammatory state (Ortega et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in miR-31 and miR-584 binding site in the angiotensinogen gene differentially influences body fat distribution in both sexes

et al. 2015

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Angiotensinogen (AGT), its active fragments and microRNA-31 (miR-31) play an important role in adipocyte differentiation. AGT contains a miR-31 polymorphic binding site. We hypothesize that the rs7079 polymorphism in the miR-31/584 binding site of the AGT gene could influence body fat distribution. A total of 751 subjects (195 men, 556 women) were enrolled in the study. The rs7079 genotypes were determined by qRT-PCR. Anthropometric measurements were taken on all subjects, who were subsequently divided into two groups: obese ([30 kg m -2 ) and non-obese (\30 kg m -2 ). Linear regression models were created to determine the contributions of sex, obesity status and rs7079 to all measured parameters. Adding the rs7079 genotype significantly contributed to the linear regression model for waist circumference (p = 0.013), hip circumference (p = 0.018) and supraspinal skin-fold thickness (p = 1 9 10 -3 ). Differences between sexes and between the obese and nonobese groups were observed. Waist circumference was lower in men carrying the A allele (p = 0.022); hip circumference was higher only in obese women carrying the A allele (p = 0.015). While men carrying the A allele had lower supraspinal skin-fold thickness (p = 0.022), this parameter was found to be higher in A allele carrying women (p = 3 9 10 -3 ). The higher total sum of skin-fold thickness in A allele carrying women was restricted to obese individuals (p = 0.028). The presence of the A allele was associated with both lower tricipital skin-fold thickness in non-obese women (p = 0.023) and a trend of higher thickness in non-obese men (p = 0.065). Significant associations of rs7079 in the AGT gene and body fat distribution were observed. The distribution followed opposing patterns in both sexes.

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“…Plasmid/viral vectors encoding miRs are encouraging strategies to replace miRs in vivo, with good transduction efficiency and minimal toxicity (Brown et al, 2006, Colin et al, 2009). Therefore, the development of miR-based therapeutics is of great interest in various diseases (Banno et al, 2014, Boon et al, 2013, Ge et al, 2014, Kornfeld et al, 2013, Sun et al, 2012). In the present study, we found that miR-146b expression was significantly decreased in IL-10 deficient mice with colitis, which prompted us to test miR-146b mimic in the treatment of colitis in IL-10 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5

et al. 2016

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The regulation of macrophage orientation pathological conditions is important but still incompletely understood. Here, we show that IL-10 and Rag1 double knockout mice spontaneously develop colitis with dominant M1 macrophage phenotype, suggesting that IL-10 regulates macrophage orientation in inflammation. We demonstrate that IL-10 stimulation induced miR-146b expression, and that the expression of miR-146b was impaired in IL-10 deficient macrophages. Our data show that miR-146b targets IRF5, resulting in the regulation of macrophage activation. Furthermore, miR-146b deficient mice developed intestinal inflammation with enhanced M1 macrophage polarization. Finally, miR-146b mimic treatment significantly suppresses M1 macrophage activation and ameliorates colitis development in vivo. Collectively, the results suggest that IL-10 dependent miR-146b plays an important role in the modulation of M1 macrophage orientation.

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microRNAs as a New Mechanism Regulating Adipose Tissue Inflammation in Obesity and as a Novel Therapeutic Strategy in the Metabolic Syndrome

Cited by 88 publications

References 91 publications

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity

Polymorphism in miR-31 and miR-584 binding site in the angiotensinogen gene differentially influences body fat distribution in both sexes

Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5

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