Emerging role of microRNAs in lipid metabolism

Abstract

microRNAs (miRNAs or miRs) are small non-coding RNAs that are involved in post-transcriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that miRNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of miRNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of miRNAs expression. We emphasized on several representative miRNAs that are functionally involved into lipid metabolism, including miR-33/33(⁎), miR122, miR27a/b, miR378/378(⁎), miR-34a and miR-21. Understanding the function of miRNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.

Keywords: ABCA1, adenosine triphosphate-binding cassette transporter A1; ABCG1, adenosine triphosphate-binding cassette transporter G1; AMPKα, AMP-activated protein kinase α; ATP8B1, aminophospholipid transporter, class I, type 8B, member 1; Ago2, argonaute 2; ApoA1, apolipoprotein A1; BDL, bile-duct ligation; CPT1A, carnitine palmitoyltransferase 1A; CRAT, carnitine O-acetyltransferase; CYP26, cytochrome P450 family 26; CYP3A4, cytochrome P450 family 3 subfamily A polypeptide 4; ERRγ, estrogen-related receptor gamma; FABP7, fatty acid-binding protein 7; FASN, fatty acid synthase; FGF21, fibroblast growth factor 21; FGFR1, fibroblast growth factor receptor 1; FXR, farnesoid X receptor; GABPA, GA binding protein transcription factor alpha subunit; GPC6, glypican 6; HADHB, hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase trifunctional protein, beta subunit; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; HMGCS1, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1; HNE, 4-hydroxynonenal; IGF1R, insulin-like growth factor 1 receptor; IGFBP3, insulin-like growth factor binding protein 3; INSIG1, insulin induced gene 1; LIPE, lipase hormone-sensitive; LNA, locked nucleic acids; LNPs, lipid-based nanoparticles; LPS, lipopolysaccharide; Lipid metabolism; MED13, mediator complex subunit 13; MHV68, murine γ-herpesvirus 68; MTTP, microsomal TG transfer protein; NR1D1/REV-ERBα, transcriptional repressor nuclear receptor subfamily 1 group D member 1; NRs, nuclear receptors; Nuclear receptors; PCK1, phosphoenolpyruvate carboxykinase 1; PDCD4, programmed cell death 4; PGC-1, peroxisone proliferator-activated receptor gamma coactivator; PLIN1, perilipin 1; PNA, peptide nucleic acid; PNPLA2, patatin-like phospholipase domain containing 2; PPARγ, peroxisone proliferator-activated receptor gamma; RTL1, retrotransposon-like 1; RXRα, retinoid X receptor alpha; SHP, small heterodimer partner; SIRT1, sirtuin 1; SIRT6, sirtuin 6; TG, triglyceride; TLR4, toll-like receptor 4; miRNAs or miRs, microRNAs; microRNAs; pre-miRNAs, precursor-miRNAs; pri-miRNAs, primary-miRNAs.

Graphical abstract

Figure 1

Regulatory role of miRNAs in lipid metabolism. Light green boxes highlight miRNAs involved in lipid metabolism. Blue boxes represent target genes of miRNAs. The miRNAs and their respective targets are linked by arrows.