Relationship of leaky gut-derived bacterial translocation and genetic regulation of body fat distribution (B03)

• Subject Area: Human Genetics ; Endocrinology, Diabetology, Metabolism
• Term: since 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 209933838

The proposed study will test the hypothesis that bacterial load and composition in AT reflect increased intestinal permeability, and this leads to the inflammatory status and dysfunction of AT. Moreover, these events are linked to the metabolic sequelae of obesity and altered body fat distribution in interplay with the host’s genetic background. Studies will evaluate mesenteric, visceral, epiploic and abdominal subcutaneous AT samples from 100 metabolically characterized obese individuals with and without evidence of AT inflammation, and from 25 lean controls, for presence and type of bacterial DNA by 16S rRNA gene sequencing. For verification of viable bacteria, catalyzed reporter deposition - fluorescence in situ hybridization (CARD-FISH) and scanning electron microscopy will be used. Lactulose mannitol test will be performed to measure intestinal permeability as a potential trigger of bacterial translocation and biomarkers (e.g. calprotectin) indicating intestinal permeability will be assessed. To evaluate whether the link between genetics and metabolic phenotypes related to adverse fat distribution is mediated by AT bacteria, genotypes and expression of genes associated with abdominal obesity will be analysed in relation to the individuals’ metabolic and inflammatory state as well as bacterial composition in AT. Finally, we will test the potential effect of bacterial presence in AT on adipocytes’ biology by treating human adipocytes with bacterial DNA and species affiliated in the bacterial taxa closely related to the inflammatory and adverse metabolic profile of studied subjects.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1052: Obesity Mechanisms
• Applicant Institution: Universität Leipzig
• Project Head: Professor Dr. Peter Kovacs