Dietary LPS traces influences disease expression of the diet-induced obese mouse

摘要

Lipopolysaccharides (LPS) from Gram negative bacteria are generally present in laboratory animal chow diets in unknown amounts, which has been correlated to significant immunological differences between animals receiving diets with either low or high "naturally" occurring LPS content. LPS in the blood stream has been linked to glucose intolerance through Toll-like receptor mediated release of pro-inflammatory cytokines, metabolic endotoxemia, adipose tissue inflammation. LPS uptake increases when co-administered with fat, therefore uncontrolled LPS levels in a high-fat diet may increase variation in development of disease when high-fat diets are used to induce obesity and type 2 diabetes. Three experiments were conducted, in which C57BL/6NTac mice received high-fat (60%) or low fat (10%) diets with or without LPS for 8 or 20 weeks investigating the short and long term effects. Three different doses of LPS were used to investigate dosage effect, and ampicillin to isolate the effect of dietary LPS. Dietary LPS increased LPS levels in the blood stream, and affected the level of glycated haemoglobin (HbA1c), a key parameter in this model, in a dose dependant manner (p 0.05). There was a strong tendency toward slower glucose uptake in the LPS supplemented groups once obesity was established, but the differences disappeared after 20 weeks. A high-fat diet slightly increased serum LPS and altered ileal expression of il10 and tnfa (p 0.05). In conclusion, LPS seems to affect the glucose metabolism in a time-dose dependant manner, and uncontrolled variation in LPS levels of a diet may therefore increase inter-study variation.