Reactive drug metabolites disposition in fat – University of Copenhagen


Reactive drug metabolites disposition in fat

Xenobiotic acids, such as the common drug ibuprofen, are incorporated into adipose tissue via triacylglycerols in which natural fatty acids are replaced by CoA conjugated xenobiotic acid. The impact of xenobiotic incorporation is not well established. However, concerns that incorporation of xenobiotic phospholipids may disrupt membrane function or xenobiotic diacylglycerols may have mutagenic potential have been put forward. Furthermore, xenobiotic disposition in adipose tissue represents a mechanism by which potentially toxic compounds may accumulate in the body. The stored compound may later be released as a result of dietary or hormonal change in concentrations that are higher than the original exposure. The consequences of this will be related to release rate and mechanism.

Currently, we investigate the mechanisms that cause drug disposition and storage in adipose tissue as well as the mechanisms for release of drugs from adipose tissue. Xenobiotic incorporation in adipose tissue is investigated in vitro in adipocytes that synthesizes and stores triacylglycerol. Lipids are extracted analysed by GC-MS and LC-MSπ for identification and quantification.