Adipose tissue: a master in toxicology

Conventional wisdom in the pathogenesis of obesity and related cardiometabolic, malignant and neurodegenerative diseases focuses mainly on genetic predisposition and lifestyle (high caloric foods, sedentary lifestyle, smoking). The human genome project's big promise was that it could improve our understanding of the pathogenesis and therapy of diseases. However, the genes have been found to account for only about 10% of diseases, and the remaining causes appear to be from environmental exposures, hence the exposure science emerges. Note that molecular epidemiology and toxicology may be essential partners of exposure science. Indeed, Homo sapiens recens is exposed to an overwhelming number of chemical contaminants circulating every day in the air, water, food, and general environment. The body is a well-equipped entity with capabilities to excrete water-soluble pollutants, but not as well-equipped to excrete some of the lipid-soluble xenobiotics. In the late 1990's, according to the European Environmental Agency more than 100 000 chemical compounds were registered in the European Catalogue of Commercialized Chemical Substances. Here we present data that adipose tissue may be an important participant in the environmental molecular toxicology. The discovery of adipocyte-secreted leptin in 1994 was a paradigm shift event in the study of adipose tissue. It was applauded by scientific community and thus triggered a new direction in the evaluation of endocrine function of adipose tissue, that is, adipoendocrinology. This is why the today's adipose tissue is viewed not merely as a lipid storage, but also as a dynamic secretory - endocrine and paracrine - organ, synthesizing, storing, and releasing a dazzling number of signaling proteins collectively termed adipokines. Numerous evidence demonstrates that the exposure to persistent organic pollutants (POP) may contribute to the pathogenesis of obesity and its related diseases. Noteworthy, these pollutants accumulate mainly in the adipose tissue. And xenobiotic-metabolizing cytochromes p450 (CYP ) are expressed in adipose tissue, where CYP 1A1 and CYP 1B1 can bioactivate carcinogenic polycyclic aromatic hydrocarbons and xenoestrogens. Altogether, the present review highlights an adipocentric approach in molecular toxicology. It is conceptualized as adipotoxicology, that is, the study of accumulation, metabolism, and release of xenobiotics in adipose tissue in health and disease. In effect, the adipose tissue may be a new bridge between environment and health - let us call it a master in toxicology.Adipobiology 2012; 4: 59-66