The role of DNA methylation in thermogenic adipose biology

Han, Xiao; Kang, Sona

doi:10.1080/15592294.2019.1625670

Cited by 9 publications

(9 citation statements)

References 66 publications

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“…Overall, the PDGFRα + subgroup had a lower methylation ratio compared with the CD137 + subgroup (Figure 4A, Supporting Information Figure S6B). Studies have revealed that DNA hypomethylation plays a critical role in thermogenic adipose tissue development and obesity‐related genes [27, 28]. Consistent with these statements, we discovered hypomethylated regions of the TEAD1 gene, especially in the promoter region, in the PDGFRα + subgroup compared with the CD137 + subgroup (Figure 4B,C).…”

Section: Resultssupporting

confidence: 88%

Distinct response of adipocyte progenitors to glucocorticoids determines visceral obesity via the TEAD1‐miR‐27b‐PRDM16 axis

Lv,

Xia,

et al. 2023

Obesity

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ObjectiveVisceral obesity contributes to obesity‐related complications; however, the intrinsic mechanism of depot‐specific adipose tissue behavior remains unclear. Despite the pro‐adipogenesis role of glucocorticoids (GCs) in adipogenesis, the role of GCs in visceral adiposity rather than in subcutaneous adipose tissue is not established. Because adipocyte progenitors display a striking depot‐specific pattern, the regulatory pathways of novel progenitor subtypes within different depots remain unclear. This study describes a cell‐specific mechanism underlying visceral adiposity.MethodsA diverse panel of novel depot‐specific adipose progenitors was screened in mice and human samples. The transcriptome distinction and various responses of novel progenitor subtypes of GCs were further measured using the GC receptor‐chromatin immunoprecipitation assay and RNA sequencing. The mechanism of novel subtypes was identified using transposase‐accessible chromatin analysis and bisulfite sequencing and further confirmed using precise editing of CpG methylation.ResultsPlatelet‐derived growth factor receptor α (PDGFRα+) progenitors, which were dominant in the visceral adipose tissue, were GC‐sensitive beige adipose progenitors, whereas CD137+ progenitors, which were dominant in the subcutaneous adipose tissue, were GC‐passive beige adipose progenitors. Expression of miR‐27b, an inhibitor of adipocyte browning, was significantly increased in PDGFRα+ progenitors treated with GCs. Using transposase‐accessible chromatin analysis, bisulfite sequencing, and precise editing of CpG methylation, TEA domain transcription factor 1 (TEAD1) was discovered to be uniquely hypomethylated in PDGFRα+ progenitors.ConclusionsGCs inhibited the PDGFRα+ progenitors' browning process via miR‐27b, which was transcriptionally activated by the collaboration of TEAD1 with the GC receptor. These data provide insights into the mechanism of depot‐specific variations in high‐fat diet‐induced obesity.

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Section: Resultssupporting

confidence: 88%

Distinct response of adipocyte progenitors to glucocorticoids determines visceral obesity via the TEAD1‐miR‐27b‐PRDM16 axis

Lv,

Xia,

et al. 2023

Obesity

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“…3 , F and G ). Previously, a development of brown adipocytes was linked to hypomethylation of genes responsible for mitochondrial respiratory chain and fatty acid oxidation ( 37 ). Because insulin-like growth factor 1 ( Igf1 ) is implicated in a regulation of fat deposition and body size ( 38 ), we next analyzed its expression in liver—a major organ for its production - of Dnmt3b CI/CI mice and found a small but significant reduction in transcript levels ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Decreases in different Dnmt3b activities drive distinct development of hematologic malignancies in mice

Lopušná

Nowialis

Opavska

et al. 2021

Journal of Biological Chemistry

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DNA methylation regulates gene transcription and is involved in various physiological processes in mammals, including development and hematopoiesis. It is catalyzed by DNA methyltransferases including Dnmt1, Dnmt3a, and Dnmt3b. For Dnmt3b, its effects on transcription can result from its own DNA methylase activity, the recruitment of other Dnmts to mediate methylation, or transcription repression in a methylation-independent manner. Low-frequency mutations in human DNMT3B are found in hematologic malignancies including cutaneous T-cell lymphomas, hairy cell leukemia, and diffuse large B-cell lymphomas. Moreover, Dnmt3b is a tumor suppressor in oncogene-driven lymphoid and myeloid malignancies in mice. However, it is poorly understood how the different Dnmt3b activities contribute to these outcomes. We modulated Dnmt3b activity in vivo by generating Dnmt3b +/− mice expressing one wild-type allele as well as Dnmt3b +/CI and Dnmt3b CI/CI mice where one or both alleles express catalytically inactive Dnmt3b CI . We show that 43% of Dnmt3b +/− mice developed T-cell lymphomas, chronic lymphocytic leukemia, and myeloproliferation over 18 months, thus resembling phenotypes previously observed in Dnmt3a +/− mice, possibly through regulation of shared target genes. Interestingly, Dnmt3b +/CI and Dnmt3b CI/CI mice survived postnatal development and were affected by B-cell rather than T-cell malignancies with decreased penetrance. Genome-wide hypomethylation, increased expression of oncogenes such as Jdp2, STAT1, and Trip13, and p53 downregulation were major events contributing to Dnmt3b +/− lymphoma development. We conclude that Dnmt3b catalytic activity is critical to prevent B-cell transformation in vivo , whereas accessory and methylation-independent repressive functions are important to prevent T-cell transformation.

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“…The phenotypic change in WAT into more energetically active cells indicates the involvement of gene expression regulation, in which internal or external regulators of WAT physiology must modify the chromatin structure or the DNA promoter methylation pattern of the target genes [ 74 , 187 , 188 ]. Recently, modifications of noncoding RNAs have been shown to act as an additional level of gene expression control [ 189 , 190 ].…”

Section: Transcriptional Control Of Browningmentioning

confidence: 99%

Control of Adipose Cell Browning and Its Therapeutic Potential

Lizcano

Arroyave

2020

Metabolites

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Adipose tissue is the largest endocrine organ in humans and has an important influence on many physiological processes throughout life. An increasing number of studies have described the different phenotypic characteristics of fat cells in adults. Perhaps one of the most important properties of fat cells is their ability to adapt to different environmental and nutritional conditions. Hypothalamic neural circuits receive peripheral signals from temperature, physical activity or nutrients and stimulate the metabolism of white fat cells. During this process, changes in lipid inclusion occur, and the number of mitochondria increases, giving these cells functional properties similar to those of brown fat cells. Recently, beige fat cells have been studied for their potential role in the regulation of obesity and insulin resistance. In this context, it is important to understand the embryonic origin of beige adipocytes, the response of adipocyte to environmental changes or modifications within the body and their ability to transdifferentiate to elucidate the roles of these cells for their potential use in therapeutic strategies for obesity and metabolic diseases. In this review, we discuss the origins of the different fat cells and the possible therapeutic properties of beige fat cells.

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The role of DNA methylation in thermogenic adipose biology

Cited by 9 publications

References 66 publications

Distinct response of adipocyte progenitors to glucocorticoids determines visceral obesity via the TEAD1‐miR‐27b‐PRDM16 axis

Distinct response of adipocyte progenitors to glucocorticoids determines visceral obesity via the TEAD1‐miR‐27b‐PRDM16 axis

Decreases in different Dnmt3b activities drive distinct development of hematologic malignancies in mice

Control of Adipose Cell Browning and Its Therapeutic Potential

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