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Krieg, L.* ; Didt, K.* ; Karkossa, I.* ; Bernhart, S.H.* ; Kehr, S.* ; Subramanian, N.* ; Lindhorst, A.* ; Schaudinn, A.* ; Tabei, S.* ; Keller, M. ; Stumvoll, M.* ; Dietrich, A.* ; von Bergen, M.* ; Stadler, P.F.* ; Laurencikiene, J.* ; Krüger, M.* ; Blüher, M. ; Gericke, M.* ; Schubert, K.* ; Kovacs, P.* ; Chakaroun, R.* ; Massier, L.*

Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance.

Gut, DOI: 10.1136/gutjnl-2021-324603 (2021)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Diabetes Mellitus ; Obesity ; Obesity Surgery; Nicotinamide Nucleotide Transhydrogenase; Gene-expression; Obese Subjects; Fat; Inflammation; Drives; Size
ISSN (print) / ISBN 0017-5749
e-ISSN 1468-3288
Zeitschrift Gut (eGut)
Verlag BMJ Publishing Group
Verlagsort British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen Deutsches Zentrum fur Diabetesforschung
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)