miR-130 Suppresses Adipogenesis by Inhibiting Peroxisome Proliferator-Activated Receptor γ Expression

Lee, Eun Kyung; Lee, Mi‐Jeong; Abdelmohsen, Kotb; Kim, Wook; Kim, Mihee M.; Srikantan, Subramanya; Martindale, Jennifer L.; Hutchison, Emmette; Kim, Hyeon Ho; Marasa, Bernard S.; Selimyan, Roza; Egan, Josephine M.; Smith, Steven R.; Fried, Susan K.; Gorospe, Myriam

doi:10.1128/mcb.00894-10

Cited by 311 publications

(237 citation statements)

References 39 publications

(37 reference statements)

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“…We did not find FAS has complementary sites of miR-130a-3p in its 39UTR. A previous study (27) and our current work (Fig. 6F), however, showed that miR-130a-3p inhibits expression of peroxisome PPARg, which is upstream regulator of FAS (28), suggesting that miR-130a-3p may regulate FAS expression via PPARg.…”

Section: Overexpression Of Mir-130a-3p Reverses Liver Steatosis In Dbcontrasting

confidence: 39%

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A Novel Function of MicroRNA 130a-3p in Hepatic Insulin Sensitivity and Liver Steatosis

Xiao

Liu

et al. 2014

Diabetes

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MicroRNAs (miRNAs) are endogenous, noncoding, short, single-stranded RNAs that are evolutionarily conserved and believed to play a role in controlling a variety of biological processes. The roles of miRNAs in insulin resistance and liver steatosis, however, are largely unknown. The objective of this study was to evaluate the roles of miR-130a in the regulation of insulin sensitivity and liver steatosis. In our current study, we observed that overexpression of miR-130a-3p increases insulin signaling in both HepG2 cells and primary mouse hepatocytes, and silencing of miR-130a-3p has the opposite effects. However, miR-130a-5p has no effect in the regulation of insulin signaling. Consistently, whole-body and hepatic insulin sensitivity are improved in mice injected with adenoviruses that overexpress miR-130a-3p. Furthermore, we provided evidence showing that growth factor receptor–bound protein 10 is required for miR-130a-3p–regulated insulin sensitivity. On the other hand, we observed that expression of miR-130a-3p is decreased in the livers of db/db mice and that adenovirus-mediated overexpression of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of which is achieved via suppressing fatty acid synthase expression in these mice. This study identifies a novel function for hepatic miR-130a-3p in the regulation of insulin sensitivity and liver steatosis.

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Section: Overexpression Of Mir-130a-3p Reverses Liver Steatosis In Dbcontrasting

confidence: 39%

“…It has been shown that miR-130a-3p potently repressed PPARg expression by targeting both the mRNA coding and 39UTRs, thereby blocking the expression of PPARg-regulated gene (27). The PPARs are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes, including FAS (28).…”

Section: Discussionmentioning

confidence: 99%

A Novel Function of MicroRNA 130a-3p in Hepatic Insulin Sensitivity and Liver Steatosis

Xiao

Liu

et al. 2014

Diabetes

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“…Interestingly, it was previously reported that miR-130 can modulate adipocyte differentiation by repressing peroxisome proliferator-activated receptor ␥, a key mediator of adipogenesis, thereby reducing adipogenesis and limiting the probability of obesity (55). This protective role of miR-130 in obesity may also translate to its protective role in DN, whereby increased levels of miR-130 impair the progression of adipogenesis and insulin resistance and decrease the potential for developing diabetes and DN.…”

Section: Rik-delmentioning

confidence: 99%

Transforming Growth Factor β1 (TGF-β1) Enhances Expression of Profibrotic Genes through a Novel Signaling Cascade and MicroRNAs in Renal Mesangial Cells

Castro

Kato

Park

et al. 2014

Journal of Biological Chemistry

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Increased TGF‐β1 expression in glomerular mesangial cells (MC) augments extracellular matrix accumulation, hypertrophy and pro‐fibrotic genes during the progression of diabetic nephropathy (DN), a debilitating renal complication of diabetes. microRNAs (miRNAs) play key roles in the pathogenesis of DN by modulating the actions of TGF‐β1 to enhance the expression of pro‐fibrotic genes like collagen. In this study, we found a significant decrease in the expression of key members of the miR‐130 and miR‐30 families in mouse MC (MMC) treated with TGF‐β1. In parallel there was a decrease in host genes 2610318N02RIK (RIK, miR‐130b host gene) and NF‐YC (miR‐30e* host gene), suggesting host gene‐dependent expression of these miRNAs. TGF‐β receptor1 (TGF‐βR1), was identified as a target of miR‐130b. Interestingly, the RIK promoter contains three NF‐YC binding sites and was regulated by NF‐YC, a potential target of miR‐216a which was also up‐regulated by TGF‐β1. Therefore, a novel cascade, ↑TGF‐β1>↑miR‐216a>↓NF‐YC>↓RIK (↓miR‐130b) may up‐regulate TGF‐βR1 to augment expression of TGF‐β1 target fibrotic genes. miR‐130 and miR‐30e* were down‐regulated, whereas TGF‐βR1, as well as the pro‐fibrotic genes COLIVa1, COLXIIa1, CTGF and PAI‐1 were up‐regulated by TGF‐β1 in MMC and in the glomeruli of streptozotocin injected diabetic mice, supporting in vivo relevance. Together, these results demonstrate a novel miRNA‐ and their host gene‐mediated cascade initiated by TGF‐β1 which results in the up‐regulation of pro‐fibrotic factors such as TGF‐βR1 and collagens associated with the progression of DN. Grant Funding Source: Supported by NIH R01 DK081705 and ADA 7‐10‐MI‐07

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“…The microRNA-17-92 cluster induces and accelerates adipocyte differentiation by suppressing expression of the pivotal cell cycle regulator Rb2/p130 [52]. In addition, let-7, microRNA-27, microRNA-130, microRNA-138, microRNA-369-5p, and microRNA-448 inhibit adipogenesis which results in a decrease in triglycerides and down-regulation of adipogenic factors [53,[58][59][60]. Similarly, microRNA-21 stalls adipogenesis by inhibiting the TGF-β signaling pathway and microRNA-143 acts in the similar fashion through down-regulating ERK-5 function [54].…”

Section: Micrornas Are Important For Adipose Tissue Functionmentioning

confidence: 99%

MicroRNA Regulated Macrophage Activation in Obesity

Kamanemi¹,

Ying²,

Bazer³

et al. 2013

J Nutr Food Sci

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Obesity and many other metabolic disorders, including type 2 diabetes and atherosclerosis, have conventionally been viewed as lipid storage disorders caused by over nutrition. Research has demonstrated that the obesity associated chronic low-grade tissue inflammation and oxidative stress is crucial factors in the initiation, propagation, and development of these metabolic disorders. Disruption in the normal functioning of the immune system and its interaction with host tissue cells makes it difficult to treat these diseases. Macrophages play critical roles in the development of insulin resistance and tissue inflammation, particularly through a unique shift in polarized activation status from an anti-inflammatory M2 function in lean adipose tissues to proinflammatory M1 activation in adipose tissues of obese individuals. Compelling evidence demonstrated the significance of microRNAs as important regulators in the immune system network. Our recent research has demonstrated that microRNA-223 is a crucial regulator of obesity associated insulin resistance through regulation of macrophage polarization in adipose tissue. This review highlights the importance of various microRNAs and their roles played in the polarization of macrophages which could be targeted for development of new therapeutic strategies to treat obesity associated diseases.

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miR-130 Suppresses Adipogenesis by Inhibiting Peroxisome Proliferator-Activated Receptor γ Expression

Cited by 311 publications

References 39 publications

A Novel Function of MicroRNA 130a-3p in Hepatic Insulin Sensitivity and Liver Steatosis

A Novel Function of MicroRNA 130a-3p in Hepatic Insulin Sensitivity and Liver Steatosis

Transforming Growth Factor β1 (TGF-β1) Enhances Expression of Profibrotic Genes through a Novel Signaling Cascade and MicroRNAs in Renal Mesangial Cells

MicroRNA Regulated Macrophage Activation in Obesity

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