ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation

Chen, Hu; Yuan, Renqiang; Zhang, Xumeng; Chen, Luxi; Zhou, Xingyu; Yuan, Zhuning; Nie, Yaping; Li, Ming; Mo, Delin; Chen, Yaosheng

doi:10.1016/j.bbagrm.2016.07.010

Cited by 25 publications

(27 citation statements)

References 42 publications

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“…The DEX is an additive of differentiation cocktail generally used for adipogenic differentiation of stem cells along with insulin (Jeon et al 2011b ; Shivakumar et al 2016 ). The mouse 3T3-L1 preadipocytes used as a control cells for adipogenesis in this study were also readily differentiated into adipocytes with massive accumulation of lipid molecules in the cytoplasm when cultured in the medium containing DEX and insulin, and similar observations were made in the previous studies (Chen et al 2016 ). The A-DMEM is a widely applied basal medium that include insulin and other molecules for the in vitro cell culture of various mammalian cells.…”

Section: Discussionsupporting

confidence: 86%

Inhibition of cell growth by cellular differentiation into adipocyte-like cells in dexamethasone sensitive cancer cell lines

Kim

Moon

Lee

et al. 2018

Animal Cells and Systems

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The stress responses in human body lead to secretion of cortisol hormone. The present study investigated the cellular responses on cell growth and cellular differentiation into adipocytes by exposure of synthetic stress hormone, dexamethasone (DEX) in various human cancer and normal cells. After prolonged exposure of cells with 1 μg/ml DEX for 2 weeks, population doubling time (PDT) was significantly (P < .05) increased by inhibited cell growth in A-549 and MCF-7 cancer cells, and was unchanged in MDA-MB-231 cancer cells, normal MRC-5 fibroblasts, umbilical cord matrix-derived mesenchymal stem cells (UCMSCs) and dental papilla tissue-derived mesenchymal stem cells (DSCs). Whereas, PDT was significantly (P < .05) decreased in U87-MG cancer cells by increased cell growth. Glucose uptake was significantly (P < .05) increased in all the cancer cell lines compared to that in normal cell lines. Further, adiposome-like vesicles were noted in A-549 and MCF-7 cancer cells indicating retarded cell growth by DEX treatment, and the vesicles were stained with Oil-Red O solution. Further, the expression of adipocyte-specific genes such as glucose transporter type 4 (GLUT4), glucocorticoid receptors β (GRβ) and peroxisome proliferator-activated receptor γ (PPARγ) were significantly (P < .05) increased in A-549 and MCF-7 with lipid vesicles. The level of telomerase activity was found to be significantly (P < .05) downregulated in DEX-treated A-549 and MCF-7 cancer cells. Our results have clearly shown that DEX treatment induces inhibition of cell growth by differentiating into adipocyte-like cells in dexamethasone sensitive cancer cells.

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Section: Discussionsupporting

confidence: 86%

Inhibition of cell growth by cellular differentiation into adipocyte-like cells in dexamethasone sensitive cancer cell lines

Kim

Moon

Lee

et al. 2018

Animal Cells and Systems

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“…Reducing the acetylation of nSREBP‐1c by SIRT1 increases nSREBP‐1c lipogenic activity 30,31 . Activating transcription factor 4 (ATF4), maintains nSREBP‐1c protein stability by directly activating USP7, which deubiquitinates SREBP‐1c and increases its protein content 32 . Here, our results indicate that Smurf1 preserves nSREBP‐1c stability by inhibiting degradation from Fbw7a.…”

Section: Discussionmentioning

confidence: 63%

Smurf1 aggravates non‐alcoholic fatty liver disease by stabilizing SREBP‐1c in an E3 activity‐independent manner

et al. 2020

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Non‐alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders which are characterized by the accumulation of excessive lipid in hepatocytes. The precise pathogenesis of NAFLD is very complicated and remains largely unknown. Smad ubiquitination regulatory factor 1 (Smurf1) is crucial for numerous processes including bone homeostasis, embryogenesis, and pathogenic autophagy. In this study, we found that liver steatosis was alleviated in Smurf1‐deficient mice fed with high‐fat diet (HFD) for 19 weeks. The deletion of Smurf1 reduced the accumulation of lipid droplets and triglycerides in hepatocytes. The stability of sterol regulatory element‐binding protein‐1c (SREBP‐1c), a key transcription factor that mediates de novo lipogenesis, was markedly reduced in Smurf1‐deficient mice. The mechanistic study showed that Smurf1 interacts with SREBP‐1c and protects SREBP‐1c from ubiquitination and degradation by preventing the binding of SREBP‐1c to its ubiquitin E3 ligase Fbw7a. Thus, our study presented an E3 ligase catalytic activity‐independent function of Smurf1 in the fatty liver development.

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“…A previous study showed the same trend in hBMMSCs [ 43 ]. Several studies demonstrated that ATF4 is involved in lipid metabolism [ 46 – 49 ]. Overexpression of ATF4 promoted adipogenesis and lipogenesis [ 49 ], and ATF4 depletion decreased adipocyte differentiation [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies demonstrated that ATF4 is involved in lipid metabolism [ 46 – 49 ]. Overexpression of ATF4 promoted adipogenesis and lipogenesis [ 49 ], and ATF4 depletion decreased adipocyte differentiation [ 46 ]. Our study seems to obtain a different result from the others, but because a microRNA could target different genes, and one gene could be regulated by different microRNAs, overexpressing miR-214 may activate other pathways to promote the adipogenesis of hPDLSCs, which should be further studied.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4

Yao

Zhao

et al. 2017

Stem Cells International

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Periodontitis is the main cause of adult tooth loss. Stem cell-based tissue engineering has become a promising therapy for periodontitis treatment. To date, human periodontal ligament stem cells (hPDLSCs) have been shown to be a favorable source for tissue engineering, but modulatory mechanisms of hPDLSCs remain unclear. Approximately 60% of mammalian genes are the targets of over 2000 miRNAs in multiple human cell types, and miRNAs are able to influence various biological processes in the human body, including bone formation. In this study, we found that after osteogenic induction, miR-214 was significantly decreased in hPDLSCs; therefore, we examined the effects of miR-214 on osteogenic differentiation. Computational miRNA target prediction analyses and luciferase reporter assays revealed that activating transcription factor 4 (ATF4) is a direct target of miR-214. We prepared cells overexpressing miR-214 and found that miR-214 negatively regulates osteogenic differentiation of hPDLSCs. For the target of miR-214, ATF4 protein expression level was decreased after induction. In conclusion, we found that miR-214-ATF4 axis is a novel pathway for regulating hPDLSC osteogenic differentiation.

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ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation

Cited by 25 publications

References 42 publications

Inhibition of cell growth by cellular differentiation into adipocyte-like cells in dexamethasone sensitive cancer cell lines

Inhibition of cell growth by cellular differentiation into adipocyte-like cells in dexamethasone sensitive cancer cell lines

Smurf1 aggravates non‐alcoholic fatty liver disease by stabilizing SREBP‐1c in an E3 activity‐independent manner

MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4

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