1417-P: Gut Microbiome Translocation to Visceral Adipose Tissue Promotes Recruitment of Adipose-Specific Neutrophils in Human Obesity

Abstract

Neutrophils protect against invading bacteria, and their unique role in adipose tissue inflammation and insulin resistance (IR) in obesity is increasingly recognized. We found that visceral adipose tissue (VAT) of obese (n=83) compared to lean (n=13) individuals had higher neutrophil abundance, correlating with IR. The obese subjects had elevated circulating plasma zonulin, a marker of intestinal permeability, and lipopolysaccharide-binding protein (LPSBP) , a marker of bacterial presence, consistent with evidence suggesting that changes in the microbiome and gut permeability in obesity permits the entry of gut bacteria and bacterial products into the circulation. Therefore, we tested for bacterial presence in VAT under sterile conditions. 16s rRNA analyses revealed that the family Streptococcaceae and an unnamed genus in the family Ruminococaceae were enriched in obese VAT contrary to order Bacilliales and genus Marvinobryantia in lean VAT, majorly originating from the GI tract. To confirm whether higher bacterial load is causal for VAT neutrophil abundance in obesity, we gavaged high-fat diet fed mice with fecal material from an obese human, which increased neutrophil, but not macrophage recruitment to VAT. As VAT is highly vascularized, we used RNA-seq to compare the gene expression signature of VAT neutrophils to peripheral blood neutrophils to eliminate the possibility that VAT neutrophils were circulating cells. Evidently, VAT neutrophils had a differential activation state compared to the circulating neutrophils, with a distinct gene expression pattern representing upregulated inflammatory, chemotactic, extracellular matrix, and ROS generation pathways. Overall, we find that that increased gut bacterial translocation enhances the recruitment of VAT specific neutrophils in obesity offering novel targets for managing VAT inflammation and comorbidities of obesity. Disclosure D.Shantaram: None. N.F.Williams: None. D.Spakowicz: None. W.Hsueh: None. A.M.Blaszczak: None. R.Hoyd: None. A.Smith: None. L.Antwi: None. J.Z.Liu: None. V.P.Wright: None. D.Bradley: None. Y.Liu: None.