Identification of a novel human long non-coding RNA that regulates hepatic lipid metabolism by inhibiting SREBP-1c

Duan, Li; Cheng, Min; Niu, Yuqiang; Chi, Xiaojing; Liu, Xiuying; Fan, Jingjing; Fan, Huishou; Chang, Yongsheng; Yang, Wei

doi:10.7150/ijbs.16635

Cited by 81 publications

(67 citation statements)

References 30 publications

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“…Mechanistically, lncHR1 regulates hepatic lipid metabolism by suppressing SREBP1c promoter activity and negatively regulating SREBP1c and FAS expression. 34 …”

Section: Lncrnas In Hepatic Lipid and Glucose Metabolismmentioning

confidence: 99%

Long non-coding RNA in liver metabolism and disease: Current status

Zhao

Liangpunsakul

et al. 2017

Liver Research

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Long non-coding RNAs (lncRNAs) are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames (with rare exceptions). Herein, we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases. We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism, as well as cholestatic liver disease. lncLSTR, Lnc18q22.2, SRA, HULC, MALAT1, lncLGR, MEG3, and H19, lncHR1, lnc-HC, APOA1-AS, DYNLRB2-2, and LeXis are included in the discussion.

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“…Mechanistically, lncHR1 regulates hepatic lipid metabolism by suppressing SREBP1c promoter activity and negatively regulating SREBP1c and FAS expression. 34 …”

Section: Lncrnas In Hepatic Lipid and Glucose Metabolismmentioning

confidence: 99%

Long non-coding RNA in liver metabolism and disease: Current status

Zhao

Liangpunsakul

et al. 2017

Liver Research

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“…Overexpression of lncHR1 in mice decreased the expression of SREBP-1c and reduced hepatic and circulating triglyceride levels. However, whether lncHR1 exerts its effects upon the SREBP-1c promoter by direct binding to the DNA or through secondary mediators remains to be clarified [29]. The mechanism by which another hepatic lncRNA, LeXis, represses the expression of cholesterol biosynthetic genes in the liver is better understood.…”

Section: Long Noncoding Rnas Regulating the Sterol Regulatory Elementmentioning

confidence: 99%

“…Elevated triglyceride levels in the circulation are associated with metabolic syndrome and cardiovascular disease [43]. LncRNAs regulating the synthesis and clearance of triglycerides are thus of interest for the generation of novel therapeutic approaches to treat dyslipidemias [29]. …”

Section: Long Non-coding Rnas Regulating Triglyceride Metabolismmentioning

confidence: 99%

Long noncoding RNAs in lipid metabolism

Solingen

Scacalossi

Moore

2018

Current Opinion in Lipidology

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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.

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“…However, LncRNAs have diverse mechanisms of action, and most of them still need to be further explored [17].There have been many reports showed that many LncRNAs are involved in the occurrence and development of diabetes and the regulation of lipid metabolism, with different mechanisms [18,19].…”

Section: Introductionmentioning

confidence: 99%

High glucose aggravates lipid deposition in glomerular endothelial cells by LXRs/LncRNAOR13C9/ABCA1 pathway

Xiao¹,

Wang²,

Zhou³

et al. 2020

Preprint

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Background Lipid metabolism disorder is closely related to diabetic nephropathy (DN), but the mechanism remains unclear. The aim of this study was to investigate the effect of high glucose on intracellular accumulation of lipids and to clarify the possible mechanism. Methods We found that in human glomerular endothelial cells (GEnCs), cholesterol could reduce cell activity, lead to abnormal lipid deposition in cells and high glucose can aggravate lipid deposition under high cholesterol load. Results CCK8 showed that soluble cholesterol could reduce GEnCs cells activity. Oil red O staining and cholesterol quantification experiment showed that the intracellular lipid deposition did not obvious after the intervention of high glucose (HG), but the intracellular lipid deposition increased under HG combined with high cholesterol (HC). The results of RT-qPCR,WB and immunofluorescence experiment showed the expression of ABCA1 in HC group increased significantly. However, compared with the HC group, the expression of ABCA1in the HG and HC group were decreased. And then we found HG affected ABCA1 up-regulation by LXRs. Based on Gene Microarray, we found that LXRs regulation of ABCA1 transcription requires the involvement of LncRNAOR13C9. Conclusions HG could enhance intracellular lipid deposition by interfering with cellular response to HC to up-regulate the expression of ABCA1, and HG blocked the expression of ABCA1 by down-regulating LXRs, and LncRNAOR13C9 also played an important role in this process. It further elucidate the pathogenesis of DN and provide a new target for the prevention and treatment of DN.

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Identification of a novel human long non-coding RNA that regulates hepatic lipid metabolism by inhibiting SREBP-1c

Cited by 81 publications

References 30 publications

Long non-coding RNA in liver metabolism and disease: Current status

Long non-coding RNA in liver metabolism and disease: Current status

Long noncoding RNAs in lipid metabolism

High glucose aggravates lipid deposition in glomerular endothelial cells by LXRs/LncRNAOR13C9/ABCA1 pathway

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