Objective Human white adipose tissue (AT) is
a metabolically active organ with distinct depot-
specific functions. Despite their locations close to the
gastrointestinal tract, mesenteric AT and epiploic AT
(epiAT) have only scarcely been investigated. Here, we
aim to characterise these ATs in-depth and estimate their
contribution to alterations in whole-body metabolism.
Design Mesenteric, epiploic, omental and abdominal
subcutaneous ATs were collected from 70 patients with
obesity undergoing Roux-en-Y gastric bypass surgery.
The metabolically well-characterised cohort included
nine subjects with insulin sensitive (IS) obesity, whose
AT samples were analysed in a multiomics approach,
including methylome, transcriptome and proteome
along with samples from subjects with insulin resistance
(IR) matched for age, sex and body mass index (n=9).
Findings implying differences between AT depots in these
subgroups were validated in the entire cohort (n=70) by
quantitative real-time PCR.
Results While mesenteric AT exhibited signatures
similar to those found in the omental depot, epiAT was
distinct from all other studied fat depots. Multiomics
allowed clear discrimination between the IS and IR states
in all tissues. The highest discriminatory power between
IS and IR was seen in epiAT, where profound differences
in the regulation of developmental, metabolic and
inflammatory pathways were observed. Gene expression
levels of key molecules involved in AT function, metabolic
homeostasis and inflammation revealed significant
depot- specific differences with epiAT showing the
highest expression levels.
Conclusion Multi- omics epiAT signatures reflect
systemic IR and obesity subphenotypes distinct from
other fat depots. Our data suggest a previously
unrecognised role of human epiploic fat in the context of
obesity, impaired insulin sensitivity and related diseases.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:90420 |
| Date | 11 March 2024 |
| Creators | Krieg, Laura, Didt, Konrad, Karkossa, Isabel, Bernhart, Stephan H, Kehr, Stephanie, Subramanian, Narmadha, Lindhorst, Andreas, Schaudinn, Alexander, Tabei, Shirin, Keller, Maria, Stumvoll, Michael, Dietrich, Arne, von Bergen, Martin, Stadler, Peter F, Laurencikiene, Jurga, Krüger, Martin, Blüher, Matthias, Gericke, Martin, Schubert, Kristin, Kovacs, Peter, Chakaroun, Rima, Massier, Lucas |
| Publisher | BMJ Publishing Group |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 0017-5749, 1468-3288, 10.1136/gutjnl-2021-324603 |
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