Diet-induced obesity results in impaired oral tolerance induction.

Abstract

Obesity increases the risk of several diseases, such as type 2 diabetes mellitus and cardiovascular disease. Obesity also affects the immune system. When dietary lipids are transported via the lymphatics, they pass the mesenteric lymph nodes (mLNs). In these secondary lymphoid organs, immune responses towards pathogens are generated, or tolerance against harmless antigens is induced. In this study, the effects of diet-induced obesity (DIO) on mLN induced oral tolerance induction were examined in C57BL/6NCrl mice. Therefore, mice were fed a high-fat or a low-fat diet for 14 weeks. After 10 weeks of feeding oral tolerance induction started, ending up in measuring the delayed-type hypersensitivity reaction, the cell subset composition and cytokine expression. We detected an impaired oral tolerance induction during DIO, but changes were reversible after switching the feed to standard chow. Thus, the altered immunological function of mLNs depends on the intake of dietary lipids. Additionally, our results show an influence of the microenvironment on the development of oral tolerance during DIO as oral tolerance was induced in transplanted peripheral lymph nodes. This indicates a functional influence of dietary lipids on stromal cells involved in immune system induction in the mLNs.