Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1136/gutjnl-2021-324603
Licence creative commons licence
Title (Primary) Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance
Author 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.
Source Titel Gut
Year 2022
Department MOLSYB
Volume 71
Issue 11
Page From 2179
Page To 2193
Language englisch
Topic T9 Healthy Planet
Supplements https://gut.bmj.com/content/early/2021/11/02/gutjnl-2021-324603#supplementary-materials
Keywords obesity; diabetes mellitus; obesity surgery
Abstract

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.

Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25409
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. (2022):
Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance
Gut 71 (11), 2179 - 2193 10.1136/gutjnl-2021-324603