肥胖及相关疾病的脂肪毒理学

S. Yanev, G. Chaldakov
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引用次数: 2

摘要

人类基因组计划的巨大希望在于,它可以提高我们对疾病发病机制和治疗方法的理解。然而,已发现基因仅占疾病的10%左右,其余原因似乎来自环境暴露,因此出现了暴露科学(暴露概念)。事实上,智人每天都暴露在空气、水、食物和一般环境中大量循环的化学污染物中。身体是一个装备齐全的实体,具有排泄水溶性污染物的能力,但不具备排泄一些脂溶性异体的能力。在这里,我们提出的数据,脂肪组织可能是一个重要的参与者在环境分子毒理学。大量证据表明,接触持久性有机污染物可能与肥胖及其相关疾病的发病机制有关。值得注意的是,这些污染物主要在脂肪组织中积累。异种代谢细胞色素p450 (CYP)在脂肪组织中表达,其中CYP1A1和CYP1B1可以生物激活致癌的多环芳烃和异种雌激素。总之,本综述强调了分子毒理学中以脂肪为中心的方法。它被定义为脂肪毒理学,即研究健康和疾病时脂肪组织中异种生物的积累、代谢和释放。生物医学评论2012;23: 53-60。
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Adipotoxicology of obesity and related diseases
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 (exposome concept) emerges. Indeed, Homo sapiens 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. Here we present data that adipose tissue may be an important participant in the environmental molecular toxicology. Numerous evidence demonstrates that the exposure to persistent organic pollutants 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 CYP1A1 and CYP1B1 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. Biomedical Reviews 2012; 23: 53-60.
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