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Obesity-induced adipose tissue dysfunction can cause low-grade inflammation and downstream obesity comorbidities. Although preadipocytes may contribute to this pro-inflammatory environment, the underlying mechanisms are unclear. We used human primary preadipocytes from body mass index (BMI) -discordant monozygotic (MZ) twin pairs to generate epigenetic (ATAC-sequence) and transcriptomic (RNA-sequence) data for testing whether increased BMI alters the subnuclear compartmentalization of open chromatin in the twins' preadipocytes, causing downstream inflammation. Here we show that the co-accessibility of open chromatin, i.e. compartmentalization of chromatin activity, is altered in the higher vs lower BMI MZ siblings for a large subset ( ~ 88.5 Mb) of the active subnuclear compartments. Using the UK Biobank we show that variants within these regions contribute to systemic inflammation through interactions with BMI on C-reactive protein. In summary, open chromatin co-accessibility in human preadipocytes is disrupted among the higher BMI siblings, suggesting a mechanism how obesity may lead to inflammation via gene-environment interactions.

Titel:	Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes.
Autor/in / Beteiligte Person:	Garske, KM ; Kar, A ; Comenho, C ; Balliu, B ; Pan, DZ ; Bhagat, YV ; Rosenberg, G ; Koka, A ; Das, SS ; Miao, Z ; Sinsheimer, JS ; Kaprio, J ; Pietiläinen, KH ; Pajukanta, P
Link:	Full Text Finder (Volltext)
Zeitschrift:	Nature communications, Jg. 14 (2023-07-14), Heft 1, S. 4214
Veröffentlichung:	[London] : Nature Pub. Group, 2023
Medientyp:	academicJournal
ISSN:	2041-1723 (electronic)
DOI:	10.1038/s41467-023-39919-y
Schlagwort:	Humans Body Mass Index Chromatin Twins, Monozygotic Inflammation genetics Obesity metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Twin Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Nat Commun] 2023 Jul 14; Vol. 14 (1), pp. 4214. <i>Date of Electronic Publication: </i>2023 Jul 14. MeSH Terms: Inflammation* / genetics ; Obesity* / metabolism ; Humans ; Body Mass Index ; Chromatin ; Twins, Monozygotic References: Nat Rev Endocrinol. 2017 Nov;13(11):633-643. (PMID: 28799554) ; Bioinformatics. 2005 May 1;21(9):2067-75. (PMID: 15657102) ; Cell Stem Cell. 2015 Dec 3;17(6):748-757. (PMID: 26637943) ; Cell. 2013 Apr 11;153(2):320-34. (PMID: 23582323) ; Nature. 2006 Dec 14;444(7121):860-7. (PMID: 17167474) ; Biomolecules. 2021 Oct 22;11(11):. (PMID: 34827568) ; Science. 2009 Oct 9;326(5950):289-93. (PMID: 19815776) ; Diabetologia. 2014 Jan;57(1):167-76. (PMID: 24100782) ; Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677) ; Twin Res Hum Genet. 2019 Oct;22(5):302-311. 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Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes.