1500-P: Oral Exposure to Cigarette Smoke Condensate Leads to Glucose Intolerance and Immune-Cell Alterations in the Gut

Introduction & Objective: Smoking is associated with an increased risk for diabetes, yet the underlying mechanism remains elusive. Since smoking correlates with many gastrointestinal tract diseases, we aimed to investigate whether cigarette smoke influences metabolic health through gut exposure.

Methods: Male C57Bl/6N and Rag2-/- mice were exposed to cigarette smoke condensate (CSC) by oral gavage (5 days/week; 0.5mg/day). Metabolic health was evaluated by glucose and insulin tolerance tests. At the end of the experiment, immune cells of different organs were characterized by flow cytometry.

Results: Mice treated with CSC exhibited impaired glucose tolerance combined with increased insulin secretion and reduced insulin sensitivity, indicative for insulin resistance. Additionally, oral exposure to CSC led to changes in colonic immune cells as characterized by increased eosinophils and inflammatory macrophages. In the liver, macrophages and monocytes were elevated, while in the adipose tissue, there was an increase in Th2 and regulatory T-cells. Rag2-/- mice, lacking mature T- and B-lymphocytes, were not protected from metabolic impairment, but rather developed glucose intolerance after a shorter period of CSC exposure.

Conclusion: Gut exposure to CSC results in glucose intolerance and insulin resistance. Additionally, oral CSC exposure leads to gut and liver inflammation. Innate immunity seems to play a central role in driving this inflammation, as mice lacking B- and T-cells demonstrate early onset of glucose intolerance. These findings point towards an immune-mediated mechanism of CSC-induced diabetes through gut exposure.