Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases

Zhang, Bin; Xu, Saijun; Liu, Jinyan; Xie, Yong; Sun, Xiulan

doi:10.3389/fphys.2021.691824

Cited by 9 publications

(13 citation statements)

References 118 publications

(121 reference statements)

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“…In 2015, the intragenic antisense lncRNA named lncRNA-tapsaki was found to be increased in kidney biopsy tissues and blood samples of 109 AKI patients using genome-wide expression pro ling technology [17]. The expression of lnc-210, lnc-atp13a4-8 and lnc-kiaa1737-2 in HKC-8 cells treated with human septic AKI plasma was higher than cells treated with septic non-AKI plasma, or healthy plasma, suggesting that the three lncRNAs are related to AKI [18,19].…”

Section: Discussionmentioning

confidence: 99%

LncRNA AK154753 promotes acute kidney ischemia-reperfusion injury via modulating the miR-345-3p/Bak and miR-708-5p/Bim axes

Deng

Zhuang

et al. 2022

Preprint

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Acute kidney injury (AKI) is one of a complex clinical syndrome with various causes and poor efficacy. The pathophysiology of AKI includes inflammation, cell apoptosis and cell death. Long noncoding RNAs (lncRNAs) represent a class of functional RNA molecules with a length of more than 200 nucleotide units (NT) and no ability to encode proteins. To identify novel molecular mechanism and potential targets for AKI, the differential expressed lncRNAs between normal and AKI tissues were analyzed with bioinformatics tool. In the present study, the mouse kidney ischemia/reperfusion injury (IRI) model and cell oxygen and glucose deprivation/ reperfusion (OGD/R) model were established. The expression levels of lncRNAs, miRNAs and mRNAs were detected by high-throughput sequencing technology. Meanwhile, lncRNA, miRNA expression levels were detected by quantitative real-time PCR. Luciferase analysis was used to further investigate the interaction between lncRNA AK154753 and miRNA, miRNA and mRNA. Western-blot were performed to test the expression of apoptosis related proteins. Furthermore, TUNEL assay was united with flow cytometry to detect cell apoptosis rate. We found lncRNA AK154753 was significantly up-regulated, while miR-345-3p and miR-708-5p were significantly down-regulated during IRI. At the same time, IRI triggered cell apoptosis both in vivo and in vitro as the evidence by upregulation of Bim/Bak/cleaved-caspase3. Luciferase analysis showed that lncRNA AK154753 could both interacted with miR-345-3p and miR-708-5p, miR-345-3p could interacted with Bak, miR-708-5p could interacted with Bim respectively. Inhibition of lncRNA AK154753 alleviated cell apoptosis along with miR-345-3p/miR-708-5p up-regulated during IRI. In conclusion, the results suggest that lncRNA AK154753 participates in the occurrence and development of acute kidney ischemia-reperfusion injury by regulating miR-345-3p/Bak, miR-708-5p/Bim axes. Inhibiting lncRNA AK154753 may represent new therapeutic modalities for renal IR injury.

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Section: Discussionmentioning

confidence: 99%

LncRNA AK154753 promotes acute kidney ischemia-reperfusion injury via modulating the miR-345-3p/Bak and miR-708-5p/Bim axes

Deng

Zhuang

et al. 2022

Preprint

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“…Long non-coding RNAs (lncRNAs), one class of non-coding regulatory RNAs with longer than 200 nucleotides, exert extensive regulatory impact on the adipose dysfunction through diverse mechanisms [12,13,23]. Most notably, growing evidence elucidates the importance of lncRNAs in the pathogenesis of vascular endothelial dysfunction in obesity [14][15][16][24][25].…”

Section: Discussionmentioning

confidence: 99%

“…Long non-coding RNAs (lncRNAs) are emerged as novel modulators in adipogenesis and adipose tissue function, thus affecting the progression of adipose dysfunction-induced diseases [12,13]. Evidence brings further insight into the importance of lncRNAs in the pathogenesis of vascular endothelial disorders in obesity.…”

Section: Introductionmentioning

confidence: 99%

Sitagliptin via the activation of AMPK/eNOS signaling improves vascular endothelial function by suppressing Creb5/lncRNA ENSMUST00000213271 axis in obese mice

Zong

Wang

Zhang

et al. 2022

Preprint

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Purpose This study aimed to investigate whether sitagliptin, a dipeptidyl peptidase-4 inhibitor, improved endothelial function by modulating lncRNAs in obese mice and clarify the underlying molecular mechanism. Methods Male C57BL/6J mice were fed with high-fat diet for four months to induce obesity and some obese mice were treated with sitagliptin for the last one month. Levels of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucagon-like peptide-1 (GLP-1) in plasma were detected by ELISA. LncRNA expression profile was analyzed via microarray. Aortic relaxations were examined by myograph. Protein expressions and phosphorylations were determined by Western blot. The differentially expressed lncRNAs were validated by qRT-PCR. Results Levels of TC and LDL were increased, concentrations of HDL and GLP-1 were decreased, and aortic endothelium-dependent relaxations were impaired in obese mice; sitagliptin reversed all above effects. Moreover, the altered expression profile of lncRNAs in the obese mouse aortae could be modulated by sitagliptin. qRT-PCR showed that lncRNA ENSMUST00000213271 was up-regulated in obese mouse aortae and endothelial cells but could be down-regulated by sitagliptin, which was consistent with microarray analysis. Importantly, we first revealed the regulatory effect of Creb5 on lncRNA ENSMUST00000213271. Furthermore, knockdown of either Creb5 or lncRNA ENSMUST00000213271 restored the activation of AMPK/eNOS in obese mouse aortic endothelial cells. Conclusion: Our results elucidate that sitagliptin ameliorated endothelial dysfunction by suppressing Creb5/lncRNA ENSMUST00000213271 and subsequently restoring AMPK/eNOS activation in obese mice. This study will provide the new evidence for the benefits of GLP-1 against vasculopathy in obesity.

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“…The study of lncRNAs in metabolism is an emerging field. In adipocytes, lncRNA have been linked to adipogenesis [34]. For example, Brown fat lncRNA 1 (Blnc1) and brown adipose tissue-enriched lncRNA 10 (lncBATE10) promote the development of thermogenic adipocytes through the regulation of Early B Cell Factor 2 (EBF2) and PGC1a, respectively [42][43][44].…”

mentioning

confidence: 99%

“…In addition to these transcriptional and posttranslational mechanisms, non-coding RNAs and especially long non-coding RNAs (lncRNAs) have emerged as potential regulators of adipocyte function [30][31][32][33][34]. The number of lncRNAs in the genome is correlated with organism complexity, they are highly tissue-specific, and their sequence is only poorly conserved between species [35].…”

mentioning

confidence: 99%

The obesity-linked human lncRNA AATBC regulates adipocyte plasticity by stimulating mitochondrial dynamics and respiration

Giroud

Kotschi

Kwon

et al. 2021

Preprint

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Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, the activation of thermogenic brown and beige adipocytes is linked to improved cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this adipocyte plasticity could help improving energy balance and weight loss. Here, we show that the long non-coding RNA (lncRNA) Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Searching for new human lncRNAs implicated in adipocyte biology we compared transcriptional profiles of human adipose tissues and cultured adipocytes and discovered that AATBC was enriched in thermogenic conditions. Using primary human adipocytes and immortalized human adipocytes we found that gain-of-function of AATBC enhanced the thermogenic phenotype whereas loss-of-function diminished this effect. The AATBC-mediated increase in mitochondrial respiration was linked to a more fragmented mitochondrial network and vice versa. While we found that AATBC is predominantly located in the nucleus, its effect on global transcription was only marginal. As AATBC is specific to humans, we expressed AATBC in adipose tissue of mice to study its systemic impact, which led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, body mass index and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.

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Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases

Cited by 9 publications

References 118 publications

LncRNA AK154753 promotes acute kidney ischemia-reperfusion injury via modulating the miR-345-3p/Bak and miR-708-5p/Bim axes

LncRNA AK154753 promotes acute kidney ischemia-reperfusion injury via modulating the miR-345-3p/Bak and miR-708-5p/Bim axes

Sitagliptin via the activation of AMPK/eNOS signaling improves vascular endothelial function by suppressing Creb5/lncRNA ENSMUST00000213271 axis in obese mice

The obesity-linked human lncRNA AATBC regulates adipocyte plasticity by stimulating mitochondrial dynamics and respiration

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