Ceramide mediates smoking‐induced insulin resistance

Abstract

Environmental toxins are increasingly implicated in adverse health outcomes. Considering the lung's apposition with the environment, we sought to test the hypothesis that ceramide functions as an intermediate between smoking and systemic insulin resistance. To determine the effect of cigarette smoke on lung ceramide metabolism, common lung cell lines including A‐549 and Beas2B were exposed to cigarette smoke extract (CSE). CSE treatment elicited a robust increase in ceramide and elevated expression of several enzymes involved with de novo ceramide synthesis. Moreover, myoblasts incubated with conditioned medium from CSE‐treated lung cells became completely insensitive to insulin stimulation, suggesting the presence of an insulin antagonist in the medium of CSE‐treated lung cells. Lastly, we measured systemic lipids in mice following nasal instillation of CSE and found an increase in muscle and hepatic ceramides; however, such findings were not observed in lung‐RAGE KO mice. This work identifies ceramide as a possible intermediate between the lung and peripheral tissues. Future work will determine the role of lung‐secreted ceramides on systemic effects in vivo, such as cardiovascular function and insulin signaling. This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI; PRR) and a BYU Mentoring Environment Grant (BTB).