A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression

Goedeke, Leigh; Vales-Lara, Frances M.; Fenstermaker, Michael; Cirera‐Salinas, Daniel; Chamorro-Jorganes, Aránzazu; Ramírez, Cristina M.; Mattison, Julie A.; Cabo, Rafael de; Suárez, Yajaira; Fernández‐Hernando, Carlos

doi:10.1128/mcb.01714-12

Cited by 128 publications

(134 citation statements)

References 43 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…As shown in Table 3, we demonstrated a significant correlation between increased circulating miR33b and decreased 2hPPBS in T2DM patients under the diet therapy. This is in agreement with a previous study that reported the inverse effect of miR-33b on glycemic control in hepatocytes through the inhibition of miR-33b's targets, including pyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), two key regulatory enzymes of hepatic gluconeogenesis (19). MiR-33b also regulates cholesterol homeostasis by targeting key transcriptional regulators of lipid metabolism, including steroid receptor coactivator 1 (SRC1), steroid receptor co-activator 3 (SRC3), nuclear transcription factor Y subunit gamma (NFYC), and nuclear receptor-interacting protein 140 (RIP140) (19).…”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Dietary Regulation of miR-33b and miR-29a in Relationship to Metabolic Biomarkers of Glucose and Lipids in Obese Diabetic Women: A Randomized Clinical Controlled Study

Mohammadi

Ebrahimi-Mameghani

Arefhosseini

et al. 2016

Iran Red Crescent Med J

View full text Add to dashboard Cite

Background: MicroRNAs have recently been introduced as epigenetic regulators of glucose and lipid metabolic pathways, which are impaired in obesity and diabetes. Objectives: We evaluated the effects of calorie-restricted diet therapy on the circulating levels of miR-33b and miR-29a in relationship to glucose and lipid metabolic parameters in obese patients with type 2 diabetes mellitus (T2DM). Methods: This randomized clinical controlled trial was performed on 30 eligible obese women with T2DM, randomly divided into two groups (control group, n = 15; diet therapy group, n = 15) for 10 weeks. Ten healthy women with normal weight were enrolled at the baseline of the study as controls. Demographic information, dietary intake, and anthropometric and biochemical indices were obtained before and after the study. Circulating miR-33b and miR-29a were assessed for all subjects using quantitative RT-PCR, and the fold change of each circulating miRNA was compared between groups. Results: The circulating levels of miR-29a and miR-33b in the diabetic women were higher (0.40-fold) and lower (1.43-fold), respectively, than normal levels. Diet therapy significantly increased the circulating level of miR-33b (P = 0.023, 0.97-fold upregulation) to normal levels. This increase was independently correlated with caloric restriction (95%CI: -0.004 to -0.0001, P = 0.022) and 2hPPBS (95%CI: -0.009 to -0.001, P = 0.035). No remarkable change was observed in circulating levels of miR-29a. Conclusions: Our findings introduced a novel therapeutic effect of diet therapy on circulating miRNAs in obese patients with T2DM. MiR-33b is an important therapeutic target in the treatment and prevention of T2DM and its complications.

show abstract

Section: Discussionsupporting

confidence: 82%

“…The most recent evidence suggests the potential of miR-33b and miR-29a as targets for the early diagnosis and treatment of glucose homeostasis disruptions and the complications of T2DM (19). MiR-33b is encoded in humans and other large mammals (13,20), but only limited studies have assessed it in human glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Dietary Regulation of miR-33b and miR-29a in Relationship to Metabolic Biomarkers of Glucose and Lipids in Obese Diabetic Women: A Randomized Clinical Controlled Study

Mohammadi

Ebrahimi-Mameghani

Arefhosseini

et al. 2016

Iran Red Crescent Med J

View full text Add to dashboard Cite

show abstract

“…CPT1A is expressed in the liver and attaches carnitine to long-chain fatty acids so they can be shuttled into mitochondria for ␤ -oxidation (23)(24)(25)(26). Activation of PPAR ␣ via therapeutic agents such as fi brates, which lower CVD risk, increases CPT1A expression as do long-chain fatty acids ( 27,28 ).…”

Section: Discussionmentioning

confidence: 99%

Methylation at CPT1A locus is associated with lipoprotein subfraction profiles

Frazier‐Wood

Aslibekyan

Absher

et al. 2014

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.orgCholesterol concentrations from lipoprotein fractions are some of the most commonly used clinical biomarkers of cardiovascular and metabolic disease risk ( 1 ). However, LDL cholesterol and HDL cholesterol concentrations do not account for all lipid-based CVD risk ( 1 ). In addition, the causal role of HDL cholesterol with CVD is debated ( 2 ). Thus, alternative lipid biomarkers of CVD are useful for gaining a more complete CVD risk profi le and for exploring the mechanisms that may underlie cardiovascular events.Within each lipoprotein fraction, the constituent particles are heterogeneous in their size and composition. The particles forming the VLDL, LDL, and HDL fractions may be further subdivided into subfractions based on their size, which partially refl ects the cholesterol content of the particle. Specifi c constellations of subfractions have been associated with insulin resistance (IR) and atherosclerosis ( 3-9 ).Currently, lipoprotein subfractions are limited in their clinical utility due to a lack of evidence that they con vey information on the likelihood of experiencing an adverse cardiovascular event over and above that of traditional anthropometric, lipid, and demographic risk factors. However, identifying the genetic factors associated with lipoprotein subfractions may provide a more thorough understanding of the pathways that regulate lipoprotein composition and metabolism and so shed light on the etiology of atherosclerosis and IR. Numerous genetic loci have been associated with lipoprotein subfractions at Abstract Lipoprotein subfractions help discriminate cardiometabolic disease risk. Genetic loci validated as associating with lipoprotein measures do not account for a large proportion of the individual variation in lipoprotein measures. We hypothesized that DNA methylation levels across the genome contribute to interindividual variation in lipoprotein measures. Using data from participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 663 for discovery and n = 331 for replication stages, respectively), we conducted the fi rst systematic screen of the genome to determine associations between methylation status at ‫ف‬ 470,000 cytosine-guanine dinucleotide (CpG) sites in CD4 + T cells and 14 lipoprotein subfraction measures. We modeled associations between methylation at each CpG site and each lipoprotein measure separately using linear mixed models, adjusted for age, sex, study site, cell purity, and family structure. We identifi ed two CpGs, both in the carnitine palmitoyltransferase-1A ( CPT1A ) gene, which reached signifi cant levels of association with VLDL and LDL subfraction parameters in both discovery and replication phases ( P < 1.1 × 10 ؊ 7 in the discovery phase, P < .004 in the replication phase, and P < 1.1 × 10 ؊ 12 in the full sample). CPT1A is regulated by PPAR ␣ , a ligand for drugs used to reduce CVD. Our associations between methylation in CPT1A and lipoprotein measures highlight the epigenetic role of this g...

show abstract

“…Most miRNAs are first transcribed into long transcripts of primary miRNAs ( pri-miRNAs) that are then processed sequentially in the nucleus by Drosha and DGCR8 to generate pre-miRNAs, and by Dicer in the cytoplasm to generate the mature ∼22 nt miRNA duplex (Lee et al, 2003) that, after strand selection, mediates the targeting activity when incorporated into the RISC complex (Chendrimada et al, 2007). There is mounting evidence that suggests that both strands, the guide or '5p' strand as well as the miRNA* (also known as the passenger or '3p' strand) have important regulatory activity (Chamorro-Jorganes et al, 2014;Goedeke et al, 2013). Approximately half of the miRNA genes can be found in intergenic regions, whereas the intragenic miRNAs are predominantly located inside introns and usually oriented on the same DNA strand of the host gene (Saini et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The miR-199/DNM regulatory axis controls receptor-mediated endocytosis

Aranda

Canfrán‐Duque

Goedeke

et al. 2015

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Small non-coding RNAs (microRNAs) are important regulators of gene expression that modulate many physiological processes; however, their role in regulating intracellular transport remains largely unknown. Intriguingly, we found that the dynamin (DNM) genes, a GTPase family of proteins responsible for endocytosis in eukaryotic cells, encode the conserved miR-199a and miR-199b family of miRNAs within their intronic sequences. Here, we demonstrate that miR-199a and miR-199b regulate endocytic transport by controlling the expression of important mediators of endocytosis such as clathrin heavy chain (CLTC), Rab5A, lowdensity lipoprotein receptor (LDLR) and caveolin-1 (Cav-1). Importantly, miR-199a-5p and miR-199b-5p overexpression markedly inhibits CLTC, Rab5A, LDLR and Cav-1 expression, thus preventing receptor-mediated endocytosis in human cell lines (Huh7 and HeLa). Of note, miR-199a-5p inhibition increases target gene expression and receptor-mediated endocytosis. Taken together, our work identifies a new mechanism by which microRNAs regulate intracellular trafficking. In particular, we demonstrate that the DNM, miR-199a-5p and miR-199b-5p genes act as a bifunctional locus that regulates endocytosis, thus adding an unexpected layer of complexity in the regulation of intracellular trafficking.

show abstract

A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression

Cited by 128 publications

References 43 publications

Dietary Regulation of miR-33b and miR-29a in Relationship to Metabolic Biomarkers of Glucose and Lipids in Obese Diabetic Women: A Randomized Clinical Controlled Study

Dietary Regulation of miR-33b and miR-29a in Relationship to Metabolic Biomarkers of Glucose and Lipids in Obese Diabetic Women: A Randomized Clinical Controlled Study

Methylation at CPT1A locus is associated with lipoprotein subfraction profiles

The miR-199/DNM regulatory axis controls receptor-mediated endocytosis

Contact Info

Product

Resources

About