Roles of MicroRNAs in Glucose and Lipid Metabolism in the Heart

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that participate in heart development and pathological processes mainly by silencing gene expression. Overwhelming evidence has suggested that miRNAs were involved in various cardiovascular pathological processes, including arrhythmias, ischemia-reperfusion injuries, dysregulation of angiogenesis, mitochondrial abnormalities, fibrosis, and maladaptive remodeling. Various miRNAs could regulate myocardial contractility, vascular proliferation, and mitochondrial function. Meanwhile, it was reported that miRNAs could manipulate nutrition metabolism, especially glucose and lipid metabolism, by regulating insulin signaling pathways, energy substrate transport/metabolism. Recently, increasing studies suggested that the abnormal glucose and lipid metabolism were closely associated with a broad spectrum of cardiovascular diseases (CVDs). Therefore, maintaining glucose and lipid metabolism homeostasis in the heart might be beneficial to CVD patients. In this review, we summarized the present knowledge of the functions of miRNAs in regulating cardiac glucose and lipid metabolism, as well as highlighted the miRNA-based therapies targeting cardiac glucose and lipid metabolism.

Keywords: glucose; heart; lipid; metabolism; microRNAs.

Figure 1

Roles of miRNAs in glucose metabolism in the heart. (A) miRNAs regulate glucose transport via modulating the expression of GLUT4 in the heart. (B) miRNAs participate in glycolysis regulation in the heart. (C) miR-195 increased acetylation of PDH to promote pyruvate and NAD⁺ convert into acetyl-CoA. (D) miR-181c and miR-210 involve in electron chain complex remodeling in cardiomyocytes by targeting and suppressing mt-COX1 and ISCU1/2. (E) miR-499, miR-761, and miR-140 regulate aerobic glucose oxidation by directly affecting mitochondrial function in the heart. (F) miRNAs regulate glycogenesis in the heart. GLUT4, glucose transporter type 4; PDH, pyruvate dehydrogenase complex; mt-COX1, cytochrome c oxidase subunit 1; ISCU1/2, iron-sulfur cluster assembly proteins.

Figure 2

Roles of miRNAs in lipid metabolism in the heart. (A) miRNAs regulate fatty acids transport via modulating the expression of CD36 in the heart. (B) miR-320 and miR-200b-3p regulate fatty acid transport via PPARγ. (C) miR-197 and miR-146b modulate Acyl-CoAs by CPT1/2, while miR-30c regulates the production of Acyl-CoAs through targeting PPARγ. (D) miR-206, miR-1, and miR-133a/b influence lipids storage in the heart. (E) miR-494-3p and miR-451 regulate lipids storage via modulating the expression of PPARγ in the heart. CD36, fatty acid translocase (FAT)/CD36; CPT1/2, carnitine palmitoyltransferase 1/2; PPARγ, peroxisome proliferator-activated receptors (PPARγ).