Human Epiploic Adipose Tissue in the Context of Obesity and Insulin Resistance: Dissertation for obtaining the academic degree Dr. med. at the Medical Faculty of the University of Leipzig

Human white adipose tissue is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric adipose tissue and epiploic adipose tissue have only scarcely been investigated. The aim is to characterise these adipose tissues in-depth and estimate their contribution to alterations in whole-body metabolism. While mesenteric adipose tissue exhibited signatures similar to those found in the omental depot, epiploic adipose tissue was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the insulin sensitive and insulin resistance states in all tissues. The highest discriminatory power between insulin sensitivity and insulin resistance was seen in epiploic adipose tissue, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in adipose tissue function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiploic adipose tissue showing the highest expression levels. Multi-omics epiploic adipose tissue signatures reflect systemic insulin resistance and obesity subphenotypes distinct from other fat depots. These data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.:Introduction...................................................................................................................3 Publication..................................................................................................................11 Summary.....................................................................................................................25 Bibliography................................................................................................................28 Supplements...............................................................................................................3