Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386524477> ?p ?o ?g. }
- W4386524477 abstract "Abstract Background First-degree relatives of type 2 diabetics (FDR) exhibit a high risk of developing type 2 diabetes (T2D) and feature subcutaneous adipocyte hypertrophy, independent of obesity. In FDR, adipose cell abnormalities contribute to early insulin-resistance and are determined by adipocyte precursor cells (APCs) early senescence and impaired recruitment into the adipogenic pathway. Epigenetic mechanisms signal adipocyte differentiation, leading us to hypothesize that abnormal epigenetic modifications cause adipocyte dysfunction and enhance T2D risk. To test this hypothesis, we examined the genome-wide histone profile in APCs from the subcutaneous adipose tissue of healthy FDR. Results Sequencing-data analysis revealed 2644 regions differentially enriched in lysine 4 tri-methylated H3-histone (H3K4me3) in FDR compared to controls (CTRL) with significant enrichment in mitochondrial-related genes. These included TFAM, which regulates mitochondrial DNA (mtDNA) content and stability. In FDR APCs, a significant reduction in H3K4me3 abundance at the TFAM promoter was accompanied by a reduction in TFAM mRNA and protein levels. FDR APCs also exhibited reduced mtDNA content and mitochondrial-genome transcription. In parallel, FDR APCs exhibited impaired differentiation and TFAM induction during adipogenesis. In CTRL APCs, TFAM -siRNA reduced mtDNA content, mitochondrial transcription and adipocyte differentiation in parallel with upregulation of the CDKN1A and ZMAT3 senescence genes. Furthermore, TFAM -siRNA significantly expanded hydrogen peroxide (H 2 O 2 )-induced senescence, while H 2 O 2 did not affect TFAM expression. Conclusions Histone modifications regulate APCs ability to differentiate in mature cells, at least in part by modulating TFAM expression and affecting mitochondrial function. Reduced H3K4me3 enrichment at the TFAM promoter renders human APCs senescent and dysfunctional, increasing T2D risk. Graphical abstract" @default.
- W4386524477 created "2023-09-08" @default.
- W4386524477 creator A5010906352 @default.
- W4386524477 creator A5025656562 @default.
- W4386524477 creator A5028448449 @default.
- W4386524477 creator A5028599620 @default.
- W4386524477 creator A5034292581 @default.
- W4386524477 creator A5034453013 @default.
- W4386524477 creator A5038081452 @default.
- W4386524477 creator A5038531696 @default.
- W4386524477 creator A5052541165 @default.
- W4386524477 creator A5057731668 @default.
- W4386524477 creator A5066298134 @default.
- W4386524477 creator A5066641927 @default.
- W4386524477 creator A5078050436 @default.
- W4386524477 creator A5084810600 @default.
- W4386524477 date "2023-09-07" @default.
- W4386524477 modified "2023-10-18" @default.
- W4386524477 title "Altered H3K4me3 profile at the TFAM promoter causes mitochondrial alterations in preadipocytes from first-degree relatives of type 2 diabetics" @default.
- W4386524477 cites W110489919 @default.
- W4386524477 cites W1801560648 @default.
- W4386524477 cites W1946178666 @default.
- W4386524477 cites W1954270231 @default.
- W4386524477 cites W1968197570 @default.
- W4386524477 cites W1968931043 @default.
- W4386524477 cites W1969819233 @default.
- W4386524477 cites W1973938271 @default.
- W4386524477 cites W1974814942 @default.
- W4386524477 cites W1974899635 @default.
- W4386524477 cites W1984173288 @default.
- W4386524477 cites W1989797259 @default.
- W4386524477 cites W1995161836 @default.
- W4386524477 cites W2002973721 @default.
- W4386524477 cites W2003474842 @default.
- W4386524477 cites W2004233590 @default.
- W4386524477 cites W2013246050 @default.
- W4386524477 cites W2015416439 @default.
- W4386524477 cites W2017840637 @default.
- W4386524477 cites W2024392277 @default.
- W4386524477 cites W2028834965 @default.
- W4386524477 cites W2029533936 @default.
- W4386524477 cites W2047160399 @default.
- W4386524477 cites W2051772622 @default.
- W4386524477 cites W2060431825 @default.
- W4386524477 cites W2067322059 @default.
- W4386524477 cites W2075033432 @default.
- W4386524477 cites W2083748438 @default.
- W4386524477 cites W2084482942 @default.
- W4386524477 cites W2099755819 @default.
- W4386524477 cites W2110330424 @default.
- W4386524477 cites W2114978842 @default.
- W4386524477 cites W2124595203 @default.
- W4386524477 cites W2124864540 @default.
- W4386524477 cites W2133938268 @default.
- W4386524477 cites W2141917949 @default.
- W4386524477 cites W2149127304 @default.
- W4386524477 cites W2150981747 @default.
- W4386524477 cites W2158348804 @default.
- W4386524477 cites W2162080206 @default.
- W4386524477 cites W2164088240 @default.
- W4386524477 cites W2164644435 @default.
- W4386524477 cites W2172343141 @default.
- W4386524477 cites W2180790011 @default.
- W4386524477 cites W2269815321 @default.
- W4386524477 cites W2608981870 @default.
- W4386524477 cites W2743155225 @default.
- W4386524477 cites W2767130291 @default.
- W4386524477 cites W2767770944 @default.
- W4386524477 cites W2801335865 @default.
- W4386524477 cites W2886159477 @default.
- W4386524477 cites W2944549000 @default.
- W4386524477 cites W2950768628 @default.
- W4386524477 cites W2952198659 @default.
- W4386524477 cites W2952357134 @default.
- W4386524477 cites W2967052232 @default.
- W4386524477 cites W3003265560 @default.
- W4386524477 cites W3022432727 @default.
- W4386524477 cites W3027187303 @default.
- W4386524477 cites W3031038667 @default.
- W4386524477 cites W3034686031 @default.
- W4386524477 cites W3035490969 @default.
- W4386524477 cites W3099940335 @default.
- W4386524477 cites W3120724236 @default.
- W4386524477 cites W3135319225 @default.
- W4386524477 cites W3135866223 @default.
- W4386524477 cites W3183323355 @default.
- W4386524477 cites W3210452762 @default.
- W4386524477 cites W4211132455 @default.
- W4386524477 cites W4240161198 @default.
- W4386524477 cites W4281654595 @default.
- W4386524477 cites W4292488030 @default.
- W4386524477 cites W4293103577 @default.
- W4386524477 doi "https://doi.org/10.1186/s13148-023-01556-z" @default.
- W4386524477 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37679776" @default.
- W4386524477 hasPublicationYear "2023" @default.
- W4386524477 type Work @default.
- W4386524477 citedByCount "0" @default.
- W4386524477 crossrefType "journal-article" @default.
- W4386524477 hasAuthorship W4386524477A5010906352 @default.
- W4386524477 hasAuthorship W4386524477A5025656562 @default.