Long noncoding RNAs in lipid metabolism

Abstract

Purpose of review Noncoding RNAs have emerged as important regulators of cellular and systemic lipid metabolism. In particular, the enigmatic class of long noncoding RNAs have been shown to play multifaceted roles in controlling transcriptional and posttranscriptional gene regulation. In this review, we discuss recent advances, current challenges and future opportunities in understanding the roles of lncRNAs in the regulation of lipid metabolism during health and disease. Recent findings Despite comprising the majority of the transcriptionally active regions of the human genome, lncRNA functions remain poorly understood, with fewer than 1% of human lncRNAs functionally characterized. Broadly defined as nonprotein coding transcripts greater than 200 nucleotides in length, lncRNAs execute their functions by forming RNA–DNA, RNA–protein, and RNA–RNA interactions that regulate gene expression through diverse mechanisms, including epigenetic remodeling of chromatin, transcriptional activation or repression, posttranscriptional regulation of mRNA, and modulation of protein activity. It is now recognized that in lipid metabolism, just as in other areas of biology, lncRNAs operate to regulate the expression of individual genes and gene networks at multiple different levels. Summary The complexity revealed by recent studies showing how lncRNAs can alter systemic and cell-type-specific cholesterol and triglyceride metabolism make it clear that we have entered a new frontier for discovery that is both daunting and exciting.

Long non‐coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes

“…[1][2][3][4] Hepatic lipid metabolism is tightly regulated through a delicate interplay of hormones (such as insulin), nuclear receptors (such as LXR), numerous cellular signalling pathways (such as PI3K/AKT/ mTOR) and hepatic transcription factors (such as MLXIPL/ChREBP and SREBPs). [12][13][14][15] In this study, we investigated the role of lncRNA H19 in regulating hepatic lipid metabolism. Emerging evidence suggests that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), may play an important role in liver metabolism and metabolic diseases.…”

Novel Lipid Long Intervening Noncoding RNA, Oligodendrocyte Maturation‐Associated Long Intergenic Noncoding RNA, Regulates the Liver Steatosis Gene Stearoyl‐Coenzyme A Desaturase As an Enhancer RNA

“…This is partly through the SREBP transcription factors, which are the master regulators of cellular lipid and cholesterol processes, with SREBP1c preferentially activating the fatty acid synthesis pathway . Recent studies have demonstrated the role of lincRNAs in regulating and helping regulate SREBPs in their functions . For instance, metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1), the nucleus‐specific lincRNA, inhibits degradation of SREBP1c protein by preventing its ubiquitination in the nucleus .…”

“…As advances in deep and high‐throughput sequencing have emerged, novel players have been identified in lipid biology, including the identification of a unique group of noncoding genes called long noncoding RNAs (lncRNAs) . LncRNAs are >200 nucleotides long, show tissue and cell‐type specificity, and can differentially regulate signaling pathways .…”

“…LncRNAs are >200 nucleotides long, show tissue and cell‐type specificity, and can differentially regulate signaling pathways . Understanding their biology has provided insight into new ways in which known key metabolic genes and proteins are regulated beyond previously described mechanisms; such novel ways include acting as scaffolds to complex proteins and enhancer RNAs (eRNAs) and modifying chromatin states . This has included the role of lncRNAs in the regulation of cholesterol and lipid pathways .…”

Genetic Association of The CYP7A1 Gene with Duck Lipid Traits

“…CYP7A1 as a target gene of LXRs, its low-level expression causes cholesterol catabolism disorder and cholic acid synthesis reduction. Based on the above research results, CYP7A1 signaling has been mentioned to participate in lipid metabolism, and a variety of molecules including LXRα, SREBP-1c, FXR, FAS, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), lecithin cholesterol acyltransferase (LCAT), and the scavenger receptor CD36 were involved, and then regulate the dynamic balance of serum TC and TG concentrations through fatty deposition (body fatty and IMF) and oxidative decomposition (Chiang 2003;van Solingen et al 2018;Zhang et al 2018). Thus, different haplotypes may cause the differentiating expression of CYP7A1 lead to the differential expression of genes involved in lipid metabolism, and all of these genes together affect intramuscular fat (IMF) content of chest muscles, percentage of abdominal fat (AFP), serum triglycerides (TG) and total cholesterol (TCH) concentrations.…”