MiR-33 and Aging: Implications for Metabolic Syndrome

MiR-33 和衰老：对代谢综合征的影响

• 批准号: 8536576
• 负责人: Leigh Goedeke
• 金额: $ 4.22万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-02 至 2015-07-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536576
• 关键词: 3' Untranslated Regions; ATP-Binding Cassette Transporters; Accounting; Address; Aging; Antisense Oligonucleotides; Apoptosis; Atherosclerosis; Attention; Base Pairing; Binding; Binding Proteins; Biochemical Pathway; Biology; Cardiology; Cardiovascular Diseases; Cardiovascular system; Carnitine; Carnitine O-Palmitoyltransferase; Carrier Proteins; Cell Line; Cells; Cellular biology; Cessation of life; Cholesterol; Cholesterol Homeostasis; Coenzyme A; Data; Development; Diet; Disease; Down-Regulation; Dyslipidemias; Ensure; Enzyme Inhibition; Enzymes; Equilibrium; Essential Fatty Acids; Fatty Acids; Fatty acid glycerol esters; Functional RNA; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Growth; Health; Heart Diseases; Hepatocyte; High Density Lipoproteins; Human; Hypertension; Hypertriglyceridemia; In Vitro; Individual; Insulin; Insulin Resistance; Insulin Signaling Pathway; Laboratories; Lipids; Liver; Mediating; Metabolic Diseases; Metabolic Pathway; Metabolic syndrome; Metabolism; MicroRNAs; Molecular; Molecular Biology; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Obesity; Oxidoreductase; Pathway interactions; Pharmaceutical Preparations; Play; Post-Transcriptional Regulation; Process; Publishing; Quality of life; Regulation; Regulatory Element; Regulatory Pathway; Research; Risk Factors; Role; SRE-1 binding protein; SRE-2 binding protein; Sterols; Stroke; Syndrome; Therapeutic; Very low density lipoprotein; Work; age related; aged; base; blood glucose regulation; cholesterol trafficking; fatty acid metabolism; fatty acid oxidation; feeding; glucose metabolism; human IRS2 protein; in vivo; insulin sensitivity; insulin signaling; interest; lipid metabolism; lipoprotein cholesterol; lipoprotein triglyceride; mortality; novel; novel therapeutic intervention; overexpression; oxidation; phosphorothioate; prevent; therapeutic target

DESCRIPTION (provided by applicant): The metabolism of cholesterol and fatty acids, essential components of many biochemical pathways, is tightly regulated at the cellular level. Insufficient or excess levels can be detrimental to cells and are associated with aging-related diseases such as atherosclerosis, type 2 diabetes, and metabolic syndrome. Many regulatory pathways exist to ensure that cholesterol and fatty acid levels are balanced. In particular, recent findings have revealed a crucial role for small non-coding RNAs (miRNAs) in the post-transcriptional control of cholesterol and lipoprotein-related genes. Of note is microRNA-33 (miR-33), an intronic miRNA located within the sterol regulatory element-binding protein (SREBP) gene, one of the master regulators of cholesterol and fatty acid metabolism. miR-33 regulates cholesterol efflux and high density lipoprotein (HDL) formation in concert with the SREBP host genes, suggesting an important role for miRNAs in the regulation of cholesterol metabolism. miR-33 has also recently been to shown to regulate fatty acid metabolism and insulin signaling. miR-33 binds and represses key enzymes involved in the regulation of fatty acid oxidation, including carnitine O-octaniltransferase (CROT), carnitine palmitoyltransferase 1A (CPT1a), and hydroxyacyl-CoA-dehydrogenase (HADHB). In addition, miR-33 also targets the insulin receptor substrate 2 (IRS2), an essential component of the insulin- signaling pathway. Overexpression of miR-33 reduces both fatty acid oxidation and insulin signaling in hepatic cell lines, whereas endogenous inhibition of miR-33 increases these two metabolic pathways. In this proposal, we hypothesize that miR-33 regulates pathways controlling three of the risk factors of metabolic syndrome, including levels of HDL, triglycerides, and insulin signaling and that miR-33 may be useful as a therapeutic target to treat this growing health concern.

描述（由申请人提供）：胆固醇和脂肪酸的代谢是许多生化途径的重要组成部分，在细胞水平上受到严格调节。维生素d含量不足或过量都会对细胞有害，并与动脉粥样硬化、2型糖尿病和代谢综合征等与衰老有关的疾病有关。存在许多调节途径来确保胆固醇和脂肪酸水平的平衡。特别是最近