MicroRNAs 33, 122, and 208: a potential novel targets in the treatment of obesity, diabetes, and heart-related diseases

Alrob, Osama Abo; Khatib, Said Y.; Naser, Saleh A.

doi:10.1007/s13105-016-0543-z

Cited by 30 publications

(20 citation statements)

References 72 publications

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“…Earlier studies showed that miRNA-142 (miR-142), a hematopoietic miR (14) is critical for governing T cell functions (15)(16)(17), macrophage differentiation (18), IL-6 expression in DCs (14)(15)(16), and CD4 + DC homeostasis (19). miRs have been shown to alter metabolic processes that are central to various disease processes (20)(21)(22)(23)(24)(25)(26)(27). However, it remains unknown whether miR-mediated regulation of immune responses is linked to their ability to regulate metabolic reprogramming.…”

Section: Introductionmentioning

confidence: 99%

miR-142 controls metabolic reprogramming that regulates dendritic cell activation

Sun¹,

Oravecz-Wilson²,

Bridges³

et al. 2019

Journal of Clinical Investigation

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Section: Introductionmentioning

confidence: 99%

miR-142 controls metabolic reprogramming that regulates dendritic cell activation

Sun¹,

Oravecz-Wilson²,

Bridges³

et al. 2019

Journal of Clinical Investigation

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“…MicroRNAs can have anti-fibrotic functions, pro-fibrotic functions, or serve as MF biomarkers [ 2 , 4 ]. MiR-33a, a highly conserved microRNA ubiquitously expressed in CFs [ 5 ], is a potential therapeutic target for cardiovascular diseases because of its correlation with high-density lipoprotein cholesterol (HDL-C) [ 6 ]. Anti-miR33 therapy inhibits mitochondrial respiration and ATP production, which in conjunction with increased ABCA1 expression, works to promote macrophage cholesterol efflux and reduce atherosclerosis [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-33 promotes myocardial fibrosis by inhibiting MMP16 and stimulating p38 MAPK signaling

et al. 2018

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Myocardial fibrosis occurs in the late stages of many cardiovascular diseases, and appears to be stimulated by various microRNAs (miRNAs). We previously found that miR-33 may stimulate cardiac remodeling. Here, we examined the involvement of miR-33 in myocardial fibrosis. Proximal left coronary descending artery occlusion was performed in rat, and antagomiR-33a was injected. Primary cardiac fibroblasts were cultured and transfected with miR-33a mimics and inhibitors. miR-33a levels were increased in the rat after surgery, and collagen deposition and heart fibrosis were observed in vivo. Inhibition of miR-33a suppressed fibroblast proliferation, reduced the mRNA and protein levels of collagen-related markers in vitro and in vivo, and rescued the histological damage in vivo. A dual-luciferase reporter system showed that matrix metalloproteinase 16 (MMP16) gene was the direct target of MiR-33a. These results suggest that miR-33 promoted myocardial fibrosis by inhibiting MMP16 and stimulating p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MiR-33 may act as a novel therapeutic target for treating myocardial fibrosis.

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“…In this study, the abundance of these miRNAs widely varied among the experimental samples from different mouse strains; the miRNA expression pattern in the epididymal fat of Tlr2 −/− and Tlr4 −/− mice was quite different from that in C57BL/6 and Tlr5 −/− mice. Among these miRNAs, miR-122 has recently been revealed as one of the key regulators of lipid metabolism [ 43 , 70 ]. Elevated circulating miR-122 was found be to positively associated with obesity and insulin resistance in young human adults [ 71 ] and in a murine model of obesity [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Low-Fat Diet in Obese Mice Lacking Toll-like Receptors

Rau

et al. 2018

Nutrients

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Background: This study aimed at assessing the effect of a low-fat diet (LFD) in obese mice lacking toll–like receptors (Tlr) and understanding the expression and regulation of microRNAs during weight reduction. Methods: C57BL/6, Tlr5−/−, Tlr2−/− and Tlr4−/− mice were used in this study. A group of mice were fed with a high-fat diet (HFD) (58% kcal) for 12 weeks to induce obesity (diet-induced obesity, DIO). Another group that had been fed with HFD for eight weeks (obese mice) were switched to a low-fat diet (LFD) (10.5% kcal) for the next four weeks to reduce their body weight. The control mice were fed with a standard AIN-76A diet for the entire 12 weeks. The body weight of the mice was measured weekly. At the end of the experiment, epididymal fat weight and adipocyte size were measured. The differentially expressed miRNAs in the fat tissue was determined by next-generation sequencing with real-time quantitative reverse transcription polymerase chain reaction (RT–qPCR). Target prediction and functional annotation of miRNAs were performed using miRSystem database. Results: Switching to LFD significantly reduced the body weight and epididymal fat mass in the HFD-fed C57BL/6 and Tlr5−/− mice but not in Tlr2−/− and Tlr4−/− mice. Weight reduction significantly decreased the size of adipocytes in C57BL/6 but not in the Tlr knockout mice. In Tlr2−/− and Tlr4−/− mice, feeding with HFD and the subsequent weight reduction resulted in an aberrant miRNA expression in the epididymal fat tissue unlike in C57BL/6 and Tlr5−/−. However, target prediction and functional annotation by miRSystem database revealed that all the top 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways of the dysregulated miRNAs during weight reduction in the C57BL/6 mice were also found in the regulated pathways of Tlr5−/−, Tlr2−/−, and Tlr4−/− strains. However, among these pathways, gene sets involved in arginine and proline metabolism and glutathione metabolism were mainly involved in the Tlr knockout mice but not in the C57BL/6 mice. Conclusions: In this study, we demonstrated that feeding of LFD leads to significant body weight reduction in C57BL/6 and Tlr5−/− mice, but not in Tlr2−/− and Tlr4−/− mice. Significant reduction in the size of adipocytes of epididymal fat was only found in C57BL/6, but not in Tlr5−/−, Tlr2−/−, and Tlr4−/− mice. The dysregulated miRNAs in Tlr2−/− and Tlr4−/− mice were different from those in C57BL/6 and Tlr5−/− strains. Among those miRNA-regulated pathways, arginine and proline metabolism as well as glutathione metabolism may have important roles in the Tlr knockout mice rather than in C57BL/6 mice.

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MicroRNAs 33, 122, and 208: a potential novel targets in the treatment of obesity, diabetes, and heart-related diseases

Cited by 30 publications

References 72 publications

miR-142 controls metabolic reprogramming that regulates dendritic cell activation

miR-142 controls metabolic reprogramming that regulates dendritic cell activation

MiR-33 promotes myocardial fibrosis by inhibiting MMP16 and stimulating p38 MAPK signaling

Effect of Low-Fat Diet in Obese Mice Lacking Toll-like Receptors

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