Figure 2: Pathophysiological mechanisms underlying regulation of systemic lipopolysaccharide concentrations.

06-06-2017 | Image

A high-fat diet and insulin resistance associated with obesity can both adversely alter the gut flora (microbiome dysbiosis), leading to a constitutive increase in the delivery of lipopolysaccharide-containing bacterial outer-membrane vesicles to the liver. Insulin resistance also increases gut permeability for outer-membrane vesicles and lipopolysaccharide through alterations to the endocannabinoid system (upregulation of cannabinoid receptor 1 (CB1)) and downregulation of tight-junction proteins (ZO-1 and occludin) of the gut endothelium. Inadequate clearance of lipopolysaccharide by a fatty liver, owing to low HDL cholesterol production, can lead to the presence of lipopolysaccharide in the systemic circulation. These processes result in a vicious cycle because of the diabetes-promoting and proinflammatory actions of lipopolysaccharide throughout the body. For instance, lipopolysaccharide acts as a ligand for Toll-like receptors (TLRs) and pattern-recognition receptors (PRRs) in various tissues, inducing or exacerbating insulin resistance in the liver. Modified with kind permission from Springer Science+Business Media © Mol. Cell. Biochem. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. 388 (2014), 203–210, Jayashree, B. et al., Figure 5.

Medicine Matters Rheumatology

Figure 2: Pathophysiological mechanisms underlying regulation of systemic lipopolysaccharide concentrations.