Obesity and tobacco smoking have long been implicated in the induction and inhibition of phase I metabolism by cytochrome P450 (P450) enzymes in the lung and liver. We hypothesized that mainstream and sidestream smoking would have broad effects upon P450 function, and when coupled to obesity the effects would be pronounced.  To test this we employed a multiplexed activity-based protein profiling approach to isolated lung and liver microsomes from lean and obese mice that were mainstream, sidestream, or non-smokers. Proteomic measurements of probe-labeled proteins identified organ-dependent and broader systemic effects on the function of nearly 30 P450s, with significant induction and inhibition of P450 function in lean and obese mice. These studies reveal that the combination of smoking and obesity is highly detrimental to phase I metabolic function, contributes to the known intolerance to and rapid clearance of therapeutic drugs, and increases the carcinogenic potential of tobacco smoke constituents.

Activity-based protein profiling reveals systemic effects of smoking and obesity on cytochrome P450 function

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.