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Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides
Author(s) -
Wang Weicang,
Yang Jun,
Qi Weipeng,
Yang Haixia,
Wang Chang,
Tan Bowen,
Hammock Bruce D.,
Park Yeonhwa,
Kim Daeyoung,
Zhang Guodong
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21692
Subject(s) - adipose tissue , lipoxygenase , polyunsaturated fatty acid , fatty acid , chemistry , metabolism , obesity , lipid metabolism , cytochrome p450 , fatty acid metabolism , arachidonic acid , cyclooxygenase , biochemistry , endocrinology , medicine , enzyme , biology
Objective Enzymatic metabolism of polyunsaturated fatty acids leads to formation of bioactive lipid metabolites (LMs). Previous studies have shown that obesity leads to deregulation of LMs in adipose tissues. However, most previous studies have focused on a single or limited number of LMs, and few systematical analyses have been carried out. Methods A LC‐MS/MS‐based lipidomics approach was used, which can analyze >100 LMs produced by cyclooxygenase, lipoxygenase, and cytochrome P450 (CYP) enzymes, to analyze the profile of LMs in high‐fat diet‐induced obesity in mice. Results LC‐MS/MS showed that high‐fat feeding significantly modulated profiles of LMs in adipose tissues. Among the three major polyunsaturated fatty acid metabolizing pathways (cyclooxygenase, lipoxygenase, and CYP), CYP‐derived fatty acid epoxides were the most dramatically altered LMs. Almost all types of fatty acid epoxides were reduced by 70% to 90% in adipose tissues of high‐fat diet‐fed mice. Consistent with the reduced levels of fatty acid epoxides, the gene expression of several CYP epoxygenases, including Cyp2j5 , Cyp2j6 , and Cyp2c44 , was significantly reduced in adipose tissues of high‐fat diet‐fed mice. Conclusions Results show that CYP‐derived fatty acid epoxides are the most responsive LMs in high‐fat diet‐induced obesity, suggesting that these LMs could play critical roles in obesity.