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      A New Insight into the Roles of MiRNAs in Metabolic Syndrome

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          Abstract

          Metabolic syndrome (MetS), which includes several clinical components such as abdominal obesity, insulin resistance (IR), dyslipidemia, microalbuminuria, hypertension, proinflammatory state, and oxidative stress (OS), has become a global epidemic health issue contributing to a high risk of type 2 diabetes mellitus (T2DM). In recent years, microRNAs (miRNAs), used as noninvasive biomarkers for diagnosis and therapy, have aroused global interest in complex processes in health and diseases, including MetS and its components. MiRNAs can exist stably in serum, liver, skeletal muscle (SM), heart muscle, adipose tissue (AT), and βcells, because of their ability to escape the digestion of RNase. Here we first present an overall review on recent findings of the relationship between miRNAs and several main components of MetS, such as IR, obesity, diabetes, lipid metabolism, hypertension, hyperuricemia, and stress, to illustrate the targeting proteins or relevant pathways that are involved in the progress of MetS and also help us find promising novel diagnostic and therapeutic strategies.

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          Sugar, Uric Acid, and the Etiology of Diabetes and Obesity

          The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
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            The Key Role of Epigenetics in Human Disease Prevention and Mitigation

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              Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism.

              The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes. © 2011 Macmillan Publishers Limited. All rights reserved
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                17 December 2018
                : 2018
                : 7372636
                Affiliations
                1Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
                2Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
                Author notes

                Academic Editor: Heide Schatten

                Author information
                http://orcid.org/0000-0003-1329-8814
                http://orcid.org/0000-0002-7572-2353
                Article
                10.1155/2018/7372636
                6311798
                30648107
                8830956b-b07c-4d1c-8945-8e43ae3583fc
                Copyright © 2018 Yuxiang Huang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 August 2018
                : 28 November 2018
                Funding
                Funded by: Guangdong Provincial Science and Technology Project
                Award ID: 2014A020212662
                Funded by: Science and Technology Planning Project of Southern Medical University
                Award ID: CX2016N018
                Funded by: Science and Technology Planning Project of Tianhe District, Guangzhou City
                Award ID: 201704KW011
                Funded by: Natural Science Foundation of Guangdong Province
                Award ID: 2016A030313559
                Funded by: South Wisdom Valley Innovative Research Team Program
                Award ID: CXTD-004
                Funded by: Science and Technique Program of Guangzhou
                Award ID: 201604020015
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