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MicroRNAs in Metabolic Disease
Open accessAbstract
Alterations in the metabolic control of lipid and glucose homeostasis predispose an individual to develop cardiometabolic diseases, such as type 2-diabetes mellitus and atherosclerosis. Work over the last years has suggested that microRNAs (miRNAs) play an important role in regulating these physiological processes. The contribution of miRNAs in regulating metabolism is exemplified by miR-33, an intronic miRNA encoded in the Srebp genes. miR-33 controls cellular cholesterol export and fatty acid degradation, whereas its host genes stimulate cholesterol and fatty acid synthesis. Other miRNAs, such as miR-122, also play a critical role in regulating lipid homeostasis by controlling cholesterol synthesis and lipoprotein secretion in the liver. This review article summarizes the recent findings in the field, highlighting the contribution of miRNAs in regulating lipid and glucose metabolism. We will also discuss how the modulation of specific miRNAs may be a promising strategy to treat metabolic diseases.
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“microRNAs can alter the expression of genes in insulin-producing and insulin-sensitive tissues, including the pancreas, liver, and vasculature.”
From The Vasculature in Prediabetes (2018) · cites this paper as [134]
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“The most abundant microRNA in the liver is miR-122.”
From The Vasculature in Prediabetes (2018) · cites this paper as [134]
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Singh, A. K., Aryal, B. K., Zhang, X., Fan, Y., Price, N. L., Suárez, Y., & Fernandez-Hernando, C. F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.11.026 · Cited by 55
“Dysregulation of miRNA expression or genetic variants associated with miRNAs or miRNA binding site loci have been associated with cardiometabolic diseases such as obesity, insulin resistance and atherosclerosis [6, 7].”
BackgroundSelf-citationYan, Y., Salazar, T. E., Dominguez, J. M., Nguyen, D. V., Calzi, S. L., Bhatwadekar, A. D., Qi, X., Busik, J. V., Boulton, M. E., & Grant, M. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080029 · Cited by 54
“Several studies demonstrated an important role of miRNA in metabolic regulation[47] and aging[48,49].”
BackgroundNon-coding RNAs in lipid metabolism
Zhang, X., Price, N. L., & Fernandez-Hernando, C. F. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.06.011 · Cited by 54
“metabolism and promising therapeutic targets for the treatment of CVD [8, 10-13].”
Role of microRNA-30c in lipid metabolism, adipogenesis, cardiac remodeling and cancer
Irani, S., & Hussain, M. M. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000162 · Cited by 50
Zhu, Z., Xu, Y., Su, Q.-J., Du, J., Tan, X.-L., Tu, Y., Tan, J.-W., & Jiao, H.-B. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1897-y · Cited by 49
microRNAs: A connection between cholesterol metabolism and neurodegeneration
Goedeke, L., & Fernandez-Hernando, C. F. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.034 · Cited by 49
“…cholesterol levels (i.e. SREBPs), work over the last few years has uncovered a critical role for miRNAs in controlling cholesterol homeostasis (Fernandez-Hernando et al, 2013; Fernandez-Hernando et al, 2011; Moore et al, 2010). miRNAs are small (~22 nucleotide) single-stranded, noncoding…”
BackgroundSelf-citationMicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells
Vidal‐Gómez, X., Pérez‐Cremades, D., Mompeón, A., Dantas, A. P., Novella, S., & Hermenegildo, C. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000487910 · Cited by 49
Kontaraki, J. E., Marketou, M. E., PARTHENAKIS, F. I., Maragkoudakis, S., Zacharis, E. A., Petousis, S., KOCHIADAKIS, G. E., & Vardas, P. E. (2015) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2015.07.013 · Cited by 49
Analysis of Serum miRNA Profiles of Myasthenia Gravis Patients
Nogales‐Gadea, G., Fransi, A. R., Suárez‐Calvet, X., Navas‐Madroñal, M., Rojas‐García, R., Mosquera, J. L., Díaz‐Manera, J., Querol, L., Gallardo, E., & Illa, I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091927 · Cited by 49
“These molecules are key in several cellular functions, and changes in their expression patterns have been associated with several diseases [19,20,21,22].”
BackgroundBiological roles of microRNAs in the control of insulin secretion and action
Caldérari, S., Diawara, M. R., Garaud, A., & Gauguier, D. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00079.2016 · Cited by 50
“Particular attention has focused on mechanisms associated with altered expression of miR-122, miR-33a, miR-33b, and Let-7, which illustrate specific aspects of miRNA biology (17, 71).”
BackgroundInsight into miRNAs related with glucometabolic disorder
Zhang, B., Shen, C., Zhu, B.-W., An, H., Zheng, B. J., Xu, S., Sun, J., Sun, P.-C., Zhang, W., Wang, J., et al. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.12.123 · Cited by 48
Giardina, S., Hernández‐Alonso, P., Díaz‐López, A., Salas‐Huetos, A., Salas‐Salvadó, J., & Bulló, M. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.11.014 · Cited by 47
Mechanisms contributing to adverse outcomes of COVID-19 in obesity
Sudhakar, M., Beaula, W. S., Meiyazhagan, G., & Parvathi, V. D. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04356-w · Cited by 50
MicroRNAs in cardiovascular ageing
Seeger, T., & Boon, R. A. (2015) · The Journal of Physiology · doi:10.1113/jp270557 · Cited by 48
“The role of miRs in these age-associated diseases is reviewed in Fernández-Hernando et al. (2013), Paneni et al. (2013) and Beltrami et al. (2014).”
BackgroundWang, H., Yan, C., Shi, X., Zheng, J., Deng, L., Yang, L., Yu, F., Yang, Y., & Shao, Y. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.02.013 · Cited by 43
“MicroRNAs (miRNAs) are endogenous single-stranded non-coding RNA that regulate gene expression by base pairing with target mRNAs, leading to mRNA cleavage or translational repression [7,8].”
BackgroundRetractedChung, J., Kim, K. H., Yu, N., An, S. H., Lee, S., & Kwon, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031314 · Cited by 43
MiR-486 regulates cholesterol efflux by targeting HAT1
Liu, D., Zhang, M., Xie, W., Lan, G., Cheng, H., Gong, D., Huang, C., Lv, Y.-C., Yao, F., Tan, Y. L., et al. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.11.128 · Cited by 41
Noncoding RNAs in Regulation of Cancer Metabolic Reprogramming
Yang, D., Sun, L., Li, Z., & Gao, P. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-1498-7_7 · Cited by 42
Identification of microRNA that represses IRS-1 expression in liver
Ono, K., Igata, M., Kondo, T., Kitano, S., Takaki, Y., Hanatani, S., Sakaguchi, M., Goto, R., Senokuchi, T., Kawashima, J., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191553 · Cited by 42
Baselga‐Escudero, L., Bladé, C., Ribas‐Latre, A., Casanova, E., Salvadó, M. J., Arola, L., & Arola‐Arnal, A. (2013) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2013.09.014 · Cited by 41
“In the latter, miR-33 [10,11] and miR-122 [10] have emerged as key regulators of lipid metabolism in the liver and have been related to metabolic disease [12].”
BackgroundOrtega, R., Liu, B., & Persaud, S. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310777 · Cited by 45
Posadas‐Sánchez, R., Pérez‐Hernández, N., Rodrı́guez-Pérez, J. M., Coral‐Vázquez, R. M., Roque‐Ramírez, B., Llorente, L., Lima, G., Flores-Domı́nguez, C., Villarreal-Molina, M. T., Posadas‐Romero, C., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16223 · Cited by 40
“They participate in the regulation of lipid metabolism, insulin biosynthesis, adipogenesis, endothelial dysfunction, neoangiogenesis, plaque development and rupture, as well as glucose homeostasis, among others [26-27].”
BackgroundIRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/− Mice Mediated by miR-33
Tang, C.-Y., Man, X.-F., Guo, Y., Tang, H.-N., Tang, J., Zhou, C.-L., Tan, S.-W., Wang, M., & Zhou, H.-D. (2017) · Molecules and Cells · doi:10.14348/molcells.2017.2228 · Cited by 38
“In addition, miRNAs lead dominant roles in cellular differentiation, proliferation, apoptosis, cholesterol biosynthesis, and cancer development (Fernandez-Hernando et al., 2013).”
Daimiel, L., Micó, V., Valls, R. M., Pedret, A., Motilva, M., Rubió, L., Fitó, M., Farràs, M., Covas, M. I., Solà, R., et al. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202000049 · Cited by 42
Mohany, K. M., Rugaie, O. A., Al‐Wutayd, O., & Al‐Nafeesah, A. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00829-z · Cited by 39
Protocols for the Analysis of microRNA Expression, Biogenesis, and Function in Immune Cells
Zhang, N., Hu, G., Myers, T. G., & Williamson, P. R. (2019) · Current Protocols in Immunology · doi:10.1002/cpim.78 · Cited by 39
Profiling the rainbow trout hepatic miRNAome under diet-induced hyperglycemia
Kostyniuk, D. J., Marandel, L., Jubouri, M., Dias, K., de Souza, R. F., Zhang, D., Martyniuk, C. J., Panserat, S., & Mennigen, J. A. (2019) · Physiological Genomics · doi:10.1152/physiolgenomics.00032.2019 · Cited by 38
“Given that hepatic miRNAs have emerged as important regulators of hepatic glucose metabolism (37, 48) and are indeed markers (26, 27, 36, 82) and functional contributors (22, 63, 65) of GI in mammalian models of metabolic disease by targeting intermediary metabolic pathways of glucose and lipid metabolism and/or upstr…”
BackgroundPosttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases
Pérez-García, A., Torrecilla-Parra, M., Frutos, M. F.-D., Martín-Martín, Y., Pardo, V., & Ramírez, C. M. (2022) · Biomolecules · doi:10.3390/biom12020208 · Cited by 45
“MiRNAs (miRs) are a class of small non-coding RNAs measuring 18–25 nucleotides in length that regulate gene expression at the posttranscriptional level and have an important role in many basic biological functions such as cell growth, differentiation, development, and apoptosis [73,74].”
BackgroundSelf-citationChallenging Cellular Homeostasis: Spatial and Temporal Regulation of miRNAs
van Wijk, N., Zohar, K., & Linial, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416152 · Cited by 38
Jia, L., Song, N., Yang, G.-L., Ma, Y.-X., Li, X.-T., Lu, R., Cao, H., Zhang, N., Zhu, M.-L., Wang, J., et al. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5133 · Cited by 36
“In the current study, miR-33a expression was observed to be upregulated, whilst the expression levels of ABCA1 and ABCG1 were reduced in the liver tissues of HLP rats, which further supports that ABCA1 and ABCG1 are the miR-33a target genes.”
InfluentialMicroRNA and Diabetic Complications: A Clinical Perspective
Fan, B., Luk, A. O. Y., Chan, J. C. N., & Ronald, C. W. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7318 · Cited by 37
“These changes can lead to overproduction and accumulation of extracellular matrix (ECM) culminating in fibrosis (51, 90).”
Metadata
- Authors
- Fernández-Hernando, C., Ramírez, C. M., Goedeke, L., & Suárez, Y.
- Affiliations
- From the Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY.
- New York University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-02
- Volume
- 33
- Issue
- 2
- Pages
- 178-185
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC3740757
- OpenAlex
- W2042714431
- Cited by
- 257
- References
- 67
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 12 · 2023: 12 · 2022: 21 · 2021: 15 · 2020: 18 · 2019: 21 · 2018: 24 · 2017: 25 · 2016: 21 · 2015: 21 · 2014: 30 · 2013: 21
- FWCI
- 10.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL105945, R01HL106063, R01HL107953)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- microRNA, metabolic disorders, lipid homeostasis, glucose homeostasis, type 2 diabetes, atherosclerosis, miR-33, SREBP, miR-122, cholesterol biosynthesis, lipoprotein secretion, liver, cholesterol export, fatty acid degradation, miRNA-based therapy
- MeSH terms
- Animals, Gene Expression Regulation, Glucose, Homeostasis, Humans, Insulin, Metabolic Diseases, Genetic Therapy, Signal Transduction, MicroRNAs, Carbohydrate Metabolism, Lipid Metabolism
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