MicroRNA-221-3p Regulates Angiopoietin-Like 8 (ANGPTL8) Expression in Adipocytes

Mysore, Raghavendra; Ortega, Francisco; Latorre, Jèssica; Ahonen, Maria A.; Savolainen-Peltonen, Hanna; Fischer‐Posovszky, Pamela; Wabitsch, Martin; Olkkonen, Vesa M.; Fernández‐Real, José Manuel; Haridas, Parvathi

doi:10.1210/jc.2017-00453

Cited by 25 publications

(35 citation statements)

References 50 publications

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“…A recent study showed that ANGPTL8 was downregulated in adipocytes due to the inflammation regulation; however, the mechanisms of ANGPTL8 in regulating inflammation have not been investigated. 58 In our study, a higher level of ANGPTL8 expression was detected in the more degenerative NP tissues and ANGPTL8…”

Section: Imbalance Between Ecm Metabolism and Inflammatory Responsesupporting

confidence: 55%

Angiopoietin‐like protein 8 expression and association with extracellular matrix metabolism and inflammation during intervertebral disc degeneration

Liao

Song

et al. 2019

J Cellular Molecular Medi

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Intervertebral disc degeneration (IDD) is considered the primary culprit for low back pain. Although the underlying mechanisms remain unknown, hyperactive catabolism of the extracellular matrix (ECM) and inflammation are suggested to play critical roles in IDD progression. This study was designed to elucidate the role of angiopoietin‐like protein 8 (ANGPTL8) in the progression of IDD, especially the relationship of ANGPTL8 with ECM metabolism and inflammation. A positive association between ANGPTL8 expression and degenerative grades of IDD was detected in the analysis of human nucleus pulposus tissue samples. Silencing of ANGPTL8 attenuated the degradation of the anabolic protein type collagen II, and reduced the expression of the catabolic proteins MMP3 and MMP9, and the inflammatory cytokine IL‐6 through inhibition of NF‐κB signalling activation. In addition, the effect of ANGPTL8 was evaluated in a rat model of puncture‐induced IDD. Based on the imaging results and histological examination in animal study, knockdown of ANGPTL8 was demonstrated to ameliorate the IDD progression. These results demonstrate the detrimental role of ANGPTL8 expression in the pathogenesis of IDD and may provide a new therapeutic target for IDD treatment.

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Section: Imbalance Between Ecm Metabolism and Inflammatory Responsesupporting

confidence: 55%

Angiopoietin‐like protein 8 expression and association with extracellular matrix metabolism and inflammation during intervertebral disc degeneration

Liao

Song

et al. 2019

J Cellular Molecular Medi

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“…miR-27a-3p plays an important role in adipogenesis [62], regulation of fat function [63], increase in glycogen storage [64], and regulation of insulin sensitivity [65]. miR-221-3p may affect insulin sensitivity and lipogenesis by regulating ANGPTL8 [66,67]. miR-222-3p mediates the apoptosis of adipocytes in visceral fat from obese individuals and may attenuate hyperglycemia in a diabetic mouse model [68,69].…”

Section: Discussionmentioning

confidence: 99%

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

Ding

Wang

et al. 2020

Journal of Diabetes Research

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Background. The prevalence of obesity and type 2 diabetes mellitus (T2DM) has become the most serious global public health issue. In recent years, there has been increasing attention to the role of long noncoding RNAs (lncRNAs) in the occurrence and development of obesity and T2DM. The aim of this work was to find new lncRNAs as potential predictive biomarkers or therapeutic targets for obesity and T2DM. Methods. In this study, we identified significant differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) between adipose tissue of individuals with obesity and T2DM and normal adipose tissue (absolute log 2 FC ≥ 1 and FDR < 0:05). Then, the lncRNA-miRNA interactions predicted by miRcode were further screened with a threshold of MIC > 0:2. Simultaneously, the mRNA-miRNA interactions were explored by miRWalk 2.0. Finally, a ceRNA network consisting of lncRNAs, miRNAs, and mRNAs was established by integrating lncRNA-miRNA interactions and mRNA-miRNA interactions. Results. Upon comparing adipose tissue from individuals with obesity and T2DM and normal adipose tissues, 364 significant DEmRNAs, including 140 upregulated and 224 downregulated mRNAs, were identified in GSE104674; in addition, 231 significant DEmRNAs, including 146 upregulated and 85 downregulated mRNAs, were identified in GSE133099. GO and KEGG analyses have shown that downregulated DEmRNAs in GSE104674 and GSE133099 were associated with obesity-and T2DM-related biological pathways, such as lipid metabolism, AMPK signaling, and insulin resistance. Furthermore, 28 significant DElncRNAs, including 14 upregulated and 14 downregulated lncRNAs, were found. Based on the predicted lncRNA-miRNA and mRNA-miRNA relationships, we constructed a competitive endogenous RNA (ceRNA) network, including five lncRNAs, ten miRNAs, and 15 mRNAs. KEGG-GSEA analysis revealed that four lncRNAs (FLG-AS1, SNAI3-AS1, AC008147.0, and LINC02015) in the ceRNA network were related to the biological pathways of metabolic diseases. Conclusions. Through ceRNA network analysis, our study identified four new lncRNAs that may be used as potential biomarkers and therapeutic targets of obesity and T2DM, thus laying a foundation for future clinical studies.

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“…ANGPTL8/betatrophin has shown its considerable association with diabetes and obesity as well as various metabolic biomarkers in glucose and lipid homeostasis (Wang et al 2016;Abu-Farha et al 2017). This hormone is reported to be highly enriched in human and mouse liver and adipose tissues (Chen et al 2019;von Loeffelholz et al 2017;Catalano-Iniesta et al 2020;Akimoto et al 2019;Mysore et al 2017). Previous studies focused on the roles of ANGPTL8 as a hormone that directly works on the endocrine system, while hardly any evidence showed that external mediators are involved in these processes (Siddiqa et al 2017;Wang et al 2016;Abu-Farha et al 2017;Wang et al 2017).…”

Section: Discussionmentioning

confidence: 99%

“…The angiogenin-like protein family includes eight members structurally similar to angiogenin and widely participate in the regulation of lipid metabolism, inflammation, haematopoietic stem cell activity and cancer cell invasion. ANGPTL8 is highly enriched in the human liver and various adipose tissues, whose levels were much lower in the other tissues, and recent studies suggested that ANGPTL8 showed similar tissue distribution in mice (Chen et al 2019;von Loeffelholz et al 2017;Catalano-Iniesta et al 2020;Akimoto et al 2019;Mysore et al 2017). ANGPTL8 has been reported to play a significant role in various metabolic diseases.…”

Section: Introductionmentioning

confidence: 99%

Liver-specific knockdown of ANGPTL8 alters the structure of the gut microbiota in mice

Cheng

Xiong

et al. 2020

Ann Microbiol

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Purpose To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota. Methods We constructed mice with liver-specific ANGPTL8 knockdown by using an adeno-associated virus serotype 8 (AAV8) system harbouring an ANGPTL8 shRNA. We analysed the structure and function of the gut microbiome through pyrosequencing and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction. Results Compared with controls, ANGPTL8 shRNA reduced the Simpson index and Shannon index (p < 0.01) of the gut microbiota in mice. At the phylum level, the sh-ANGPTL8 group showed a healthier gut microbiota composition than controls (Bacteroidetes: controls 67.52%, sh-ANGPTL8 80.75%; Firmicutes: controls 10.96%, sh-ANGPTL8 8.58%; Proteobacteria: controls 9.29%, sh-ANGPTL8 0.98%; F/B ratio: controls 0.16, sh-ANGPTL8 0.11). PCoA and UPGMA analysis revealed a significant difference in microbiota composition, while KEGG analysis revealed a significant difference in microbiota function between controls and the sh-ANGPTL8 group. Conclusion Our results revealed that inhibition of ANGPTL8 signalling altered the structure of the gut microbiome, which might further affect the metabolism of mice. We have thus identified ANGPTL8 as a novel hepatogenic hormone potentially involving the liver-gut axis and regulating the structure of the gut microbiota.

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MicroRNA-221-3p Regulates Angiopoietin-Like 8 (ANGPTL8) Expression in Adipocytes

Abstract: The inflammation-induced miR-221-3p regulates ANGPTL8 expression in adipocytes. This miRNA impact may become especially prominent under pathologic conditions such as morbid obesity, putatively contributing to the impaired AT lipid metabolism in metabolic disease.

Cited by 25 publications

References 50 publications

Angiopoietin‐like protein 8 expression and association with extracellular matrix metabolism and inflammation during intervertebral disc degeneration

Angiopoietin‐like protein 8 expression and association with extracellular matrix metabolism and inflammation during intervertebral disc degeneration

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

Liver-specific knockdown of ANGPTL8 alters the structure of the gut microbiota in mice

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