Epigenetic regulation of adipocyte differentiation and adipogenesis

Li, Hongxing; Xiao, Lei; Wang, Cheng; Gao, Jiali; Zhai, Yonggong

doi:10.1631/jzus.b0900401

Cited by 47 publications

(37 citation statements)

References 53 publications

(72 reference statements)

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“…4A). The results were consistent with the study of Li et al on the methylation modification levels in the promoter region of the C/EBPα gene in 3T3-L1 cells; that study showed that the promoter region of the C/EBPα gene was hypermethylated in the 3T3-L1 adipocytes, and hypermethylation was not detected in the 3T3-L1 preadipocytes [17]. The promoter region of the C/EBPα gene in pig preadipocytes was unmethylated, and the TDG gene performed demethylation functions.…”

Section: Discussionsupporting

confidence: 92%

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Zhang

Liu²,

Zhu³

et al. 2016

Cell Physiol Biochem

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Aims: To study the effect of thymine DNA glycosylase (TDG) gene knockdown on the differentiation of pig preadipocytes. Methods: Preadipocytes were obtained from subcutaneous adipose tissue from the neck of 1- to 7-day-old pigs. The TDG gene was knocked down using siRNA, and cell differentiation was induced. The mRNA expression level was measured using fluorescence quantitative PCR, and the protein expression level was determined using Western blot analysis. The DNA methylation levels in promoter regions of differentiation-related genes were also evaluated. Results: TDG gene knockdown decreased the mRNA expression levels of the peroxisome proliferator-activated receptorγ (PPARγ) and Fatty acid binding proteins 4(FABP4 Also known as aP2) genes (P<0.01), while the mRNA expression level of the CCAAT/enhancer binding protein alpha(C/EBPα) gene did not change significantly (P>0.05). In addition, after induced differentiation, the lipid droplet production significantly decreased, and the percentages of methylation in the promoter regions of C/EBPα, PPARγ, and aP2 genes were 0.9%, 80%, and 76%, respectively. In contrast, the percentages of methylation in the negative control groups were 0.5%, 67.5%, and 58%, respectively. Conclusion: TDG gene knockdown could inhibit the differentiation of pig preadipocytes and affect the DNA methylation levels of some transcription factors.

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Section: Discussionsupporting

confidence: 92%

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Zhang

Liu²,

Zhu³

et al. 2016

Cell Physiol Biochem

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“…4 This study shows the adipogenic gene expression was perturbed during early adipogenesis. Proadipogenic genes such as C/EBPβ, and C/EBPδ are known to be increased early in the differentiation process, 22,23,24 and these were all upregulated in propranolol-treated HemSCs as compared to vehicle treated HemSCs. Elevated expression levels of PPARγ were seen at the 24-hour mark, a gene that is usually expressed later in adipogenesis during terminal differentiation.…”

Section: Discussionmentioning

confidence: 94%

“…23,24 Under physiological conditions, C/EBPα is induced by C/EBPβ and C/EBPδ, and its expression is associated with terminal adipocyte differentiation. While propranolol treatment increased expression of C/EBPβ and C/EBPδ, they failed to induce C/EBPα expression.…”

Section: Discussionmentioning

confidence: 99%

Propranolol Promotes Accelerated and Dysregulated Adipogenesis in Hemangioma Stem Cells

England¹,

Hardy²,

Kitajewski³

et al. 2014

Annals of Plastic Surgery

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Background Infantile hemangiomas are the most common tumor of infancy, yet there are no FDA-approved therapeutics to date. Recently, the non-selective beta-adrenergic-blocker propranolol has been shown to be a safe and effective means of treating infantile hemangiomas, though its mechanism has yet to be elucidated. We have previously demonstrated that propranolol induces early and incomplete adipogenesis in stem cells derived from hemangiomas. We hypothesize that propranolol promotes dysregulated adipogenesis via the improper regulation of adipogenic genes. Methods Hemangioma stem cells isolated from resected infantile hemangioma specimens were treated with adipogenic medium for 1 or 4 days in either propranolol or vehicle. Cell death was measured by the incorporation of annexin V and propidium iodide by flow cytometry. Adipogenesis was assessed by visualizing lipid droplet formation by Oil Red O staining. Pro-adipogenic genes C/EBPβ, C/EBPβ, C/EBPδ, PPARδ, PPARγ, RXRα, and RXRγ were analyzed by quantitative reverse transcription and polymerase chain reaction. Results Hemangioma stem cells treated with propranolol increased lipid droplet formation compared to vehicle-treated cells indicating increased adipogenesis. Cell death as measured by FACS analysis indicated that the propranolol-treated cells died due to necrosis and not apoptosis. During adipogenesis, transcript levels of PPARδ, PPARγ, C/EBPβ, and C/EBPδ were significantly increased (p < 0.01) in propranolol-treated cells relative to control cells. In contrast, RXRα and RXRγ levels were significantly decreased (p < 0.05), and C/EBPα, a gene required for terminal adipocyte differentiation, was strongly suppressed by propranolol when compared to vehicle-treated cells (p < 0.01). Conclusions In hemangioma stem cells, propranolol accelerated dysregulated adipogenic differentiation characterized by improper adipogenic gene expression. Consistent with accelerated adipogenesis, propranolol significantly increased the expression of the pro-adipogenic genes, PPARγ , C/EBPβ and C/EBPγ compared to control. However, propranolol treatment also led to improper induction of PPARδ and suppression of C/EBPα, RXRα and RXRγ. Taken together this data indicates that propranolol promoted dysregulated adipogenesis and inhibited the hemangioma stem cells from becoming functional adipocytes, ultimately resulting in cell death. Understanding this mechanism behind propranolol's effectiveness will be a vital factor in producing more effective therapies in the future.

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“…Considerable evidence has suggested that epigenetic mechanisms, including histone methylation, are critical for adipogenic differentiation (5,14,19). For example, one study demonstrated that the histone H4 Lys-20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene was upregulated by PPAR␥ during adipogenesis, and that PR-Set7/Setd8 positively regulated the expression of PPAR␥ and its targets through H4K20 monomethylation.…”

Section: E993mentioning

confidence: 99%

G9a is transactivated by C/EBPβ to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation

Guo

Qian

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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In 3T3-L1 preadipocyte differentiation, the CCAAT/enhancer-binding protein-β (C/EBPβ) is an important early transcription factor that activates cell cycle genes during mitotic clonal expansion (MCE), sequentially activating peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα during terminal differentiation. Although C/EBPβ acquires its DNA binding activity via dual phosphorylation at about 12-16 h postinduction, the expression of PPARγ and C/EBPα is not induced until 36-72 h. The delayed expression of PPARγ and C/EBPα ensures the progression of MCE, but the mechanism responsible for the delay remains elusive. We provide evidence that G9a, a major euchromatic methyltransferase, is transactivated by C/EBPβ and represses PPARγ and C/EBPα through H3K9 dimethylation of their promoters during MCE. Inhibitor- or siRNA-mediated G9a downregulation modestly enhances PPARγ and C/EBPα expression and adipogenesis in 3T3-L1 preadipocytes. Conversely, forced expression of G9a impairs the accumulation of triglycerides. Thus, this study elucidates an epigenetic mechanism for the delayed expression of PPARγ and C/EBPα.

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Epigenetic regulation of adipocyte differentiation and adipogenesis

Cited by 47 publications

References 53 publications

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Propranolol Promotes Accelerated and Dysregulated Adipogenesis in Hemangioma Stem Cells

G9a is transactivated by C/EBPβ to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation

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