Long noncoding RNAs in lipid metabolism

Solingen, Coen van; Scacalossi, Kaitlyn R; Moore, Kathryn J.

doi:10.1097/mol.0000000000000503

Cited by 51 publications

(47 citation statements)

References 65 publications

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Cao

Shu

et al. 2019

J Cellular Molecular Medi

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Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long noncoding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up-regulated in oleic acid-induced steatosis and during the development of high-fat diet (HFD)-induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up-regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up-regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19-induced lipid accumulation in hepatocytes. Furthermore, H19-induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF-04691502. Accordingly, H19 overexpression in hepatocytes up-regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up-regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these

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Section: Introductionmentioning

confidence: 99%

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

Wang

Cao

Shu

et al. 2019

J Cellular Molecular Medi

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“…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 .…”

Section: Discussionmentioning

confidence: 99%

“…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 .…”

mentioning

confidence: 99%

“…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 .…”

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confidence: 99%

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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

Benhammou

Alvarez

et al. 2019

Hepatol Commun

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The global obesity epidemic is driving the concomitant rise in nonalcoholic fatty liver disease (NAFLD). To identify new genes involved in central liver functions, we examined liver RNA‐sequence data from 259 patients who underwent morbidly obese bariatric surgery. Of these patients, 84 had normal liver histology, 40 simple steatosis, 43 nonalcoholic steatohepatitis, and the remaining 92 patients had varying degrees of NAFLD based on liver histology. We discovered oligodendrocyte maturation‐associated long intergenic noncoding RNA (OLMALINC), a long intervening noncoding RNA (lincRNA) in a human liver co‐expression network (n = 75 genes) that was strongly associated with statin use and serum triglycerides (TGs). OLMALINC liver expression was highly correlated with the expression of known cholesterol biosynthesis genes and stearoyl‐coenzyme A desaturase (SCD). SCD is the rate‐limiting enzyme in monounsaturated fatty acids and a key TG gene that is known to be up‐regulated in liver steatosis and NAFLD and resides adjacent to OLMALINC on the human chromosome 10q24.31. Next, we functionally demonstrated that OLMALINC regulates SCD as an enhancer‐RNA (eRNA), thus describing the first lincRNA that functions as an eRNA to regulate lipid metabolism. Specifically, we show that OLMALINC promotes liver expression of SCD in cis through regional chromosomal DNA–DNA looping interactions. Conclusion: The primate‐specific lincRNA OLMALINC is a novel epigenetic regulator of the key TG and NAFLD gene SCD.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Genetic Association of The CYP7A1 Gene with Duck Lipid Traits

Zhang

Qin

Luo

et al. 2018

Preprint

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Cholesterol 7α-hydroxylase (Cyp7a1) participates in lipid metabolism of liver, and its pathway involves catabolism of cholesterol to bile acids and excretion from the body. However, little is known about the effect of the polymorphisms of CYP7A1 gene on duck lipid traits. In the present study, seven novel synonymous mutations loci in exon 2 and exon 3 of CYP7A1 gene in Cherry Valley ducks were identified using PCR production direct sequencing. One novel SNP g.1033130 C>T was predicted in exon 2. Six novel SNPs g.1034076 C>T, g.1034334 G>A, g.1034373 G>A, g.1034448 T>C, g.1034541 C>G, and g.1034550 G>A were discovered in exon 3. Six haplotypes were detected using SHEsis online analysis software, and five loci (g.1034334G>A, g.1034373G>A, g.1034448T>C, g.1034541C>G, and g.1034550G>A) were in complete linkage disequilibrium, and as a block named Locus C3. By single SNP association analysis, we found that the g.1033130 C>T locus was significantly associated with IMF, AFP, TG, and TC (P<0.01 or P<0.05) respectively, the g.1034076 C>T locus was significantly associated with AFP (P<0.05), and the locus C3 was significantly associated with TCH (P<0.05). Sixteen dipoltypes were detected by the combination of haplotypes, and demonstrated strong association with IMF, AFP, TG, and TCH (P<0.01). Therefore, our data suggested that the seven SNPs of CYP7A1 gene are potential markers for lipid homeostasis, and may be used for early breeding and selection of duck.

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Long noncoding RNAs in lipid metabolism

Cited by 51 publications

References 65 publications

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

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

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

Genetic Association of The CYP7A1 Gene with Duck Lipid Traits

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