miR‐519d Overexpression Is Associated With Human Obesity

Martinelli, Rosanna; Nardelli, Carmela; Pilone, Vincenzo; Buonomo, Tonia; Liguori, Rosario; Castanò, Ilenia; Buono, Pasqualina; Masone, Stefania; Persico, Giovanni; Forestieri, Pietro; Pastore, Lucio; Sacchetti, Lucia

doi:10.1038/oby.2009.474

Cited by 150 publications

(136 citation statements)

References 27 publications

(34 reference statements)

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“…PPARG transcripts are also repressed by miR-130, which affects human adipocyte differentiation (42). Downregulated expression of PPARA by miR-519d in humans leads to increased lipid accumulation during preadipocyte differentiation (51). KLF5 expression is repressed by miR-448, resulting in reduced expression of adipogenic genes, reduced triglyceride accumulation, and impaired adipocyte differentiation (35).…”

Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 99%

“…Microarray-based profiling of miRNA expression in adipose tissue in animal models and obese patients has provided information on collections of known miRNAs that are differentially expressed in obesity (25,26,51,81), including miRNAs consistently differentially expressed in various rodent models (e.g., miR-27a, miR-103, miR-107) and in both models and humans (e.g., miR-15a, miR-30d). An miR-29 paralog (miR29a) was differentially expressed in visceral adipose tissue between GK and control rats (26), and a series of experiments indicated altered expression of miR-125a in visceral adipose tissue of HFD mice and in 3T3-L1 adipocytes (10).…”

Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 99%

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Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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microRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs, and one transcript can be targeted by several miRNAs, resulting in complex fine-tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion, and signaling, and their role in diabetes and obesity is emerging. Their pathophysiological effects are essentially dependent on cellular coexpression with their mRNA targets, which can show tissue-specific transcriptional responses to disease conditions and environmental challenges. Current knowledge of miRNA biology and their impact on the pathogenesis of diabetes and obesity is based on experimental data documenting miRNA expression generally in single tissue types that can be correlated with expression of target mRNAs to integrate miRNA in functional pathways and gene networks. Here we present results from the most significant studies dealing with miRNA function in liver, fat, skeletal muscle, and endocrine pancreas and their implication in diabetes and obesity

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Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 99%

Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 99%

Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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“…A recent study using hypothalamic tissue from ob/ob mice, a genetically obese and leptin-deficient strain has identified changes in miR200a, miR-200b and miR-429 (Crepin et al 2014). Furthermore, within other tissue types, studies report an association of microRNA levels in adipose tissue, under high-fat diet or obesity, and in brown fat undergoing differentiation (Martinelli et al 2010;Sun et al 2011;Takanabe et al 2008). Together, the evidence from these studies suggests that expression of hypothalamic micro-RNA may also change in response to normal changes in energy availability.…”

Section: Introductionmentioning

confidence: 69%

“…This is the first study to fully characterize the transcriptome of the hypothalamus in 24-h fasting, compared to the ad lib fed animals. Given the previous published studies showing differential regulation of microRNAs in brain, adipose and other tissues conditions such as cancer or obesity, it was surprising to find so few differentially expressed microRNAs via microarray analysis and none that could be confirmed by further QPCR analysis (Fassan et al 2011;Martinelli et al 2010;McNeill and Van Vactor 2012;Roshan et al 2009;Sun et al 2011;Takanabe et al 2008). Although current database information suggests that there are only 105 microRNAs expressed in the midbrain above the detection threshold (http://www.microrna.org), we detected 536 microRNAs using the Affymetrix microarrays.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the hypothalamic transcriptome in response to food deprivation reveals global changes in long noncoding RNA, and cell cycle response genes

et al. 2015

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The hypothalamus integrates energy balance information from the periphery using different neuronal subtypes within each of the hypothalamic areas. However, the effects of prandial state on global mRNA, microRNA and long noncoding (lnc) RNA expression within the whole hypothalamus are largely unknown. In this study, mice were given either a 24-h fast, or ad libitum access to food. RNA samples were analyzed by microarray, and then a subset was confirmed using quantitative real-time PCR (QPCR). A total of 540 mRNAs were either up-or downregulated with food deprivation. Since gene ontology enrichment analyses identified several categories of mRNAs related to cell cycle processes, ten cell-cycle-related genes were further analyzed using QPCR with six confirmed to be significantly up-regulated and one downregulated in response to 24-h fasting. While 22 independent microRNAs were differentially expressed by microarray, secondary analysis by QPCR failed to confirm significant changes with fasting. There were 622 lncRNAs identified as differentially expressed, and of three tested by QPCR, two were confirmed. Overall, this is the first time that expression of hypothalamic lncRNAs has been shown to be responsive to food deprivation. In addition, this study is the first to identify a list of lncRNAs with high expression in RNA extracted from hypothalamus. Individual contributions from specific miRNA, lncRNA and mRNAs to the food deprivation response can now be further studied at the physiological and biochemical levels.

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“…Recently, extensive reports have indicated that as a major class of gene-regulatory molecules, miRNAs, are critical to various biological processes, such as tissue development, the onset of diabetes, cell differentiation, and proliferation (Ambros 2003, Martinelli et al 2010, Guo et al 2012, Bhushan et al 2013. It is well documented that miRNAs Apc is the real target of miR-135a-5p.…”

Section: Discussionmentioning

confidence: 99%

miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling

Chen¹,

Peng²,

Peng³

et al. 2014

Journal of Molecular Endocrinology

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MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as post-transcriptional regulators of fat development and adipogenesis. Adipogenic marker genes, such as CCAAT/enhancer binding protein a (Cebpa), peroxisome proliferatoractivated receptor g (Pparg), adipocyte fatty acid binding protein (Ap2), and fatty acid synthase (Fas), are regarded as the essential transcriptional regulators of preadipocyte differentiation and lipid storage in mature adipocytes. Canonical Wnt/b-catenin signaling is recognized as a negative molecular switch during adipogenesis. In the present work we found that miR-135a-5p is markedly downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-135a-5p impairs the expressions of adipogenic marker genes as well as lipid droplet accumulation and triglyceride content, indicating the importance of miR-135a-5p for adipogenic differentiation and adipogenesis. Further studies show that miR-135a-5p directly targets adenomatous polyposis coli (Apc), contributes to the translocation of b-catenin from cytoplasm to nucleus, and then activates the expressions of cyclin D1 (Ccnd1) and Cmyc, indicating the induction of canonical Wnt/b-catenin signaling. In addition, inhibition of APC with siRNA exhibits the same effects as overexpression of miR-135a-5p. Our findings demonstrate that miR-135a-5p suppresses 3T3-L1 preadipocyte differentiation and adipogenesis through the activation of canonical Wnt/b-catenin signaling by directly targeting Apc. Taken together, these results offer profound insights into the adipogenesis mechanism and the development of adipose tissue.

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miR‐519d Overexpression Is Associated With Human Obesity

Cited by 150 publications

References 27 publications

Biological roles of microRNAs in the control of insulin secretion and action

Biological roles of microRNAs in the control of insulin secretion and action

Characterization of the hypothalamic transcriptome in response to food deprivation reveals global changes in long noncoding RNA, and cell cycle response genes

miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling

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