LAUSR

Background: Cigarette smoking (CS) and obesity are leading causes of morbidity and mortality worldwide and are frequently associated. Both behaviors provoke inflammation and induce lung, metabolic, intestine and cardiovascular dysfunctions leading to e.g. chronic obstructive pulmonary disease and metabolic syndrome. However, the effect of combined exposure is not well unraveled. Objectives: We aimed to define the effect of combined exposure to CS and high fat diet (HFD) on the cardiovascular, metabolic, respiratory and intestinal functions. Moreover, we evaluate if smoking cessation may limit the dysfunctions due to this exposure. Methods: C57BL6 mice were exposed to 4 weeks of HFD followed by 12 weeks of combined exposure to CS and HFD. Then, some mice were submitted to CS cessation during 8 weeks. Metabolic, immunological and inflammatory parameters were evaluated. Results: Conjugated exposure increases lung inflammatory cell recruitment and activation as well as tissue lesions compared with exposure to CS and HFD alone. CS limits the body weight, affects adipose tissue repartition and reduces HFD-induced glucose intolerance. CS/HFD combination leads to cardiomyocyte hypertrophy. CS decreases colonic inflammation and the number of commensal bacteria in the caecum. Smoking cessation was not able to reverse these effects. Conclusion: Our murine model reproduced the human situation. While combined exposure leads to strong cardiovascular and lung dysfunctions, it had a mild impact on metabolic and intestinal compartment. In this context, CS cessation is not able to reverse the lesions related to combined exposure. We will now focus on the role of oxidative stress on these effects.