Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides

Abstract

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 highfat diet-induced obesity, suggesting that these LMs could play critical roles in obesity.

Lipidomic profiling reveals soluble epoxide hydrolase as a therapeutic target of obesity-induced colonic inflammation

“…2A) (11). GC-MS analysis showed that HFD treatment had no effect on the level of ARA or DHA in colon (SI Appendix, Table S3), and this result is in agreement with our previous study which showed that HFD had no impact on ARA levels in adipose tissues of HFD-treated mice (26). qRT-PCR showed that HFD increased expression of Ephx2 (encoding sEH) in colon tissues, while it had no effect on expression of Pla2g4a (encoding cytosolic calcium-dependent PLA 2 ) or CYP monooxygenases such as Cyp3a11, Cyp2c29, Cyp2c38, Cyp2c37, Cyp2c39, Cyp2j5, Cyp2j6, Cyp2j8, and Cyp2j9 ( Fig.…”

Long Term Egg Yolk Consumption Alters Lipid Metabolism and Attenuates Hyperlipidemia in Mice Fed a High‐Fat Diet Based on Lipidomics Analysis

“…The HFD + EY markedly lowered the content of neutral glycerolipid, such as TG and DG, in serum and FAs in liver compared with HFD. Hence, the inhibition of hepatic FAs and serum TG accumulation in HFD + EY is associated with the improvements in hyperlipidemia, which is consistent with previous studies …”

Effects of high-fat diet on plasma profiles of eicosanoid metabolites in mice

“…These results are largely in agreement with previous studies which showed that obesity induced a low-degree inflammation [37]. The profiles of LMs in adipose tissues and plasma in HFD-induced obesity are very different [10,35]. This is feasible, since most LMs are short-lived, locally produced and locally acting in response to cellular stimulation, followed with well-controlled degradation to maintain homeostasis [5,6].…”

“…It remains to determine the specific tissues and cell types involved in production of EpOMEs. It is not likely that the increased concentrations of EpOMEs in plasma are derived from adipose tissues, since studies by us and others have shown that there is a dramatic reduction of the expressions of CYP enzymes involved in biosynthesis of fatty acid epoxides, and reduced levels of CYP-derived fatty acid epoxides in adipose tissues of HFD-fed mice [10,35]. In our study, we also analyze the ratio of fatty acid epoxides to diols, which is a potential biomarker of sEH [5].…”