Project 466952

Obesity, type 2 diabetes (T2D), and non-alcoholic fatty liver disease are interlinked diseases that have high health and economic burdens. Most research associates intestinal bacteria to T2D and fatty liver disease by describing changes in the names of bacterial during obesogenic diets. An important goal is to identify bacterial processes and molecules that cause effects on host metabolism and can be manipulated to combat metabolic disease and T2D. Postbiotics are bacterial components that come from living or dead bacteria. Postbiotics such as lipopolysaccharide (LPS) can cause immune responses such as inflammation, and increased inflammation can promote metabolic dysfunction. ;Metabolic endotoxemia describes a low-level increase in blood LPS. We recently discovered that the type of LPS determines a positive or negative effect on host metabolism. However, it is not known what features of metabolic disease influence the type of LPS.Changes in the gut microbiome or gut barrier function may alter the balance or type of circulating LPS. We hypothesize that the level of blood glucose and level of body fat dictate whether LPS is detrimental or beneficial during metabolic endotoxemia. We will use control, hyperglycemic (Akita), and normoglycemic Akita (treated with chronic insulin) mice to determine if different levels of blood glucose influence the type and activity of LPS in the gut, portal, and systemic blood circulation in lean mice. Similarly, we will compare lean mice to obese mice to determine whether obesity at different ages influences metabolic endotoxemia. This research may lead to understanding which factor in metabolic disease influences a source of inflammation that contributes to aggravating metabolic disease.