Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice

Seeger, Timon; Fischer, Ariane; Muhly-Reinholz, Marion; Zeiher, Andreas M.; Dimmeler, Stefanie

doi:10.1002/oby.20852

Cited by 67 publications

(58 citation statements)

References 40 publications

(51 reference statements)

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“…Similarly, a study in mice demonstrated that miR-21 inhibition reduced obesity through the reduction of adipocyte size (35). Other reports have indicated that miR-21 regulated adipogenesis in human primary adipocytes and that its expression was positively correlated with BMI (36).…”

mentioning

confidence: 86%

Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia

Zhang

Cai

et al. 2016

Molecular Medicine Reports

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Abstract. Macrosomia, a birth weight ≥4,000 g, is associated with maternal and infant health problems. The dysregulation of microRNAs (miRNAs) in the placenta is associated with adverse birth outcomes, yet whether aberrantly expressed placental miRNAs are associated with macrosomia remains unknown. The aim of the current study was to characterize the expression of three placental miRNAs (miR-6, -21 and -143) and evaluate their association with macrosomia. The miRNA expression in placental tissues from 67 macrosomic pregnancies and 64 normal pregnancies were analyzed using reverse transcription-quantitative polymerase chain reaction. The expression of miR-21 was observed to be elevated in macrosomic placenta compared with control samples, while miR-143 expression was significantly lower than in control placenta (P<0.05). No significant differences were identified in the miR-16 expression levels between the groups (P= 0.955). Following division of miRNA expression levels by quartile, logistic regression models demonstrated that the odds of macrosomia increased with miR-21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39-32.05]; Q3, OR=4.10 (95% CI, 0.88-19.11); Q4, OR=16.19 (95% CI, 2.46-106.68). Conversely, higher levels of miR-143 expression were protective against macrosomia: Q2, OR= 0.22 (95% CI, 0.049-0.98); Q3, OR= 0.11 (95% CI, 0.024-0.55), and Q4, OR= 0.16 (95% CI, 0.032-0.79). Thus, statistical analysis demonstrated that high levels of miR-21 expression and low levels of miR-143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen-activated protein kinases signaling pathway to influence the risk of macrosomia. The results of the present study provide evidence that placental miR-21 and -143 are important in the formation of macrosomia.

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confidence: 86%

Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia

Zhang

Cai

et al. 2016

Molecular Medicine Reports

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“…The team of Prof. Dimmeler recently showed that the long-term (18 weeks) inhibition of miR-21 is effective to reduce body weight and adipocyte size in aged db/db mice [30], whereas in the liver miR-21 regulates both regeneration [31] and progression of fibrosis [32]. With regard to the impact of miRs expression on hepatic metabolism also contradictory results can be found.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs: Decoders of Dysbiosis into Metabolic Diseases?

Sérino¹

2016

J Diabetes Metab

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The identification of molecular factors bridging gut microbiota dysbiosis to alterations of host metabolism still remains a major goal in biomedical research. In fact, on one hand, there is a worldwide consensus about the systemic impact, from brain to liver, from heart to adipose tissue, of gut microbiota dysbiosis. On the other hand, beyond the microbial production of short chain fatty acids and their vast metabolic properties, little is known about the molecular mechanisms linking a change in the activity of gut microbes to a modification of host cell metabolism. In this context, microRNAs (also known as miRs) are promising molecules which could allow explaining how dysbiosis is converted into metabolic outcomes since: 1-miRs are pleiotropic regulators of gene expression, targeting multiple mRNAs at once; 2-miRs expression in specific organs such as the intestine has been demonstrated to be under the control of gut microbiota; 3-alterations in miRs expression have been found in the majority of tissues targeted by gut microbiota dysbiosis during metabolic diseases such as liver, adipose tissue, pancreas, skeletal muscle, intestine, heart and also the brain. In this review publications in the growing field of miRsbased metabolic control at a systemic level will be discussed together with a putative link with gut microbiota dysbiosis.

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“…Because miRNAs have been shown to be actively transported in microvesicles/exosomes in circulating fl uids as well as between endothelial and cardiovascular cells [ 35 , 36 ], Bang et al [ 34 , 37 ] tested the hypothesis that miRNAs could represent a paracrine cross talk between cardiac fi broblasts and cardiomyocytes. While miR-21 has been shown as a fi broblast mediator for generating hypertrophy and failure [ 38 ] and to be involved in metabolic diseases [ 39 ], the present study interestingly shows that the corresponding miR-21* is specifi cally packaged into and transported by exosomes from cardiac fi broblasts to cardiomyocytes and promotes cellular hypertrophy. In vivo studies demonstrated that miR-21* was detected in the pericardial fl uids of mice submitted to aortic constriction-induced hypertrophy and that a systemic administration of an anti-miR-21* prevented angiotensin-induced hypertrophy [ 34 ].…”

Section: Mirnas As Molecular Therapeutic Targets For Heart Failurementioning

confidence: 53%

MicroRNA Therapeutics in Cardiovascular Disease

Bril

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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MicroRNAs are endogenous single-stranded RNAs of approximately 22 nucleotides in length which decrease the level of expression of specifi c proteins. miRNAs are involved in many pathologic conditions such as cancers and neuropsychiatric and metabolic diseases. In cardiovascular diseases, miRNAs have been shown to be involved in the proliferation of cardiomyocytes and non-myocyte cardiac cells, in cardiac hypertrophy and apoptosis, in the occurrence of atrial and ventricular arrhythmias, in vascular angiogenesis and smooth muscle cell pathologies, and in atherosclerosis. In heart failure, miRNAs have been shown to promote or inhibit hypertrophy and remodeling as well as to modulate cardiac pump function. By considering a few specifi c examples illustrating the value and complexity of targeting miRNAs, this chapter will describe the key data demonstrating the potential of miRNAs either to prevent cardiac hypertrophy (miR-208) or to improve cardiac function (miR-25) in heart failure. In the biogenesis of miRNAs, a passenger strand miRNA, called miRNA*, is usually degraded. The effects of miR-21* illustrate a situation where miRNA* exhibits a biological activity. Finally, miRNAbased therapeutics is nearly reaching human trials in the cardiovascular disease area. However, several questions remain to be fully investigated to progress such therapeutic approaches successfully. These include strategies to improve druggability parameters and delivery characteristics of selected candidates as well as approaches required to demonstrate clearly the effi cacy/safety ratio of such novel therapies.

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Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice

Cited by 67 publications

References 40 publications

Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia

Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia

MicroRNAs: Decoders of Dysbiosis into Metabolic Diseases?

MicroRNA Therapeutics in Cardiovascular Disease

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