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Epigenetic Dysregul...
Epigenetic Dysregulation of the Homeobox A5 (HOXA5) Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity
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Parrillo, L. (författare)
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Spinelli, R. (författare)
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Costanzo, M. (författare)
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Florese, P. (författare)
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Cabaro, S. (författare)
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Desiderio, A. (författare)
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Prevenzano, I. (författare)
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Raciti, G. A. (författare)
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- Smith, Ulf, 1943 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Miele, C. (författare)
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Formisano, P. (författare)
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Napoli, R. (författare)
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Beguinot, F. (författare)
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(creator_code:org_t)
- 2022-02-18
- 2022
- Engelska.
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:4
- Relaterad länk:
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https://www.mdpi.com...
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Along with insulin resistance and increased risk of type 2 diabetes (T2D), lean first-degree relatives of T2D subjects (FDR) feature impaired adipogenesis in subcutaneous adipose tissue (SAT) and subcutaneous adipocyte hypertrophy well before diabetes onset. The molecular mechanisms linking these events have only partially been clarified. In the present report, we show that silencing of the transcription factor Homeobox A5 (HOXA5) in human preadipocytes impaired differentiation in mature adipose cells in vitro. The reduced adipogenesis was accompanied by inappropriate WNT-signaling activation. Importantly, in preadipocytes from FDR individuals, HOXA5 expression was attenuated, with hypermethylation of the HOXA5 promoter region found responsible for its downregulation, as revealed by luciferase assay. Both HOXA5 gene expression and DNA methylation were significantly correlated with SAT adipose cell hypertrophy in FDR, whose increased adipocyte size marks impaired adipogenesis. In preadipocytes from FDR, the low HOXA5 expression negatively correlated with enhanced transcription of the WNT signaling downstream genes NFATC1 and WNT2B. In silico evidence indicated that NFATC1 and WNT2B were directly controlled by HOXA5. The HOXA5 promoter region also was hypermethylated in peripheral blood leukocytes from these same FDR individuals, which was further revealed in peripheral blood leukocytes from an independent group of obese subjects. Thus, HOXA5 controlled adipogenesis in humans by suppressing WNT signaling. Altered DNA methylation of the HOXA5 promoter contributed to restricted adipogenesis in the SAT of lean subjects who were FDR of type 2 diabetics and in obese individuals. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Adipocyte hypertrophy
- Adipose tissue
- DNA methylation
- Epigenetic marks
- Gene expression
- Human adipogenesis
- Obesity
- Preadipocyte
- T2D familiarity
- Transcription factors
- adiponectin
- fatty acid binding protein 4
- glucose transporter 4
- homeobox protein Hox-A5
- transcription factor
- transcription factor NFAT
- unclassified drug
- vinculin
- Wnt2 protein
- adipocyte
- adipogenesis
- Article
- bisulfite sequencing
- cell differentiation
- cell isolation
- controlled study
- differential gene expression
- epigenetics
- first-degree relative
- gene
- gene silencing
- genetic transcription
- HOXA5 gene
- human
- human cell
- hypertrophy
- in vitro study
- leukocyte
- luciferase assay
- mRNA expression level
- non insulin dependent diabetes mellitus
- proadipocyte
- protein expression level
- real time polymerase chain reaction
- subcutaneous adipocyte hypertrophy
- Western blotting
- Wnt signaling
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Cells
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Till lärosätets databas
- Av författaren/redakt...
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Parrillo, L.
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Spinelli, R.
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Costanzo, M.
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Florese, P.
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Cabaro, S.
-
Desiderio, A.
-
visa fler...
-
Prevenzano, I.
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Raciti, G. A.
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Smith, Ulf, 1943
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Miele, C.
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Formisano, P.
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Napoli, R.
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Beguinot, F.
-
visa färre...
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Göteborgs universitet