Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity |
| |
Authors: | Weibin Zha Matthew L Edin Kimberly C Vendrov Robert N Schuck Fred B Lih Jawahar Lal Jat J Alyce Bradbury Laura M DeGraff Kunjie Hua Kenneth B Tomer John R Falck Darryl C Zeldin Craig R Lee |
| |
Institution: | 2. Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC;4. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX |
| |
Abstract: | Adipogenesis plays a critical role in the initiation and progression of obesity. Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have emerged as a potential therapeutic target for cardiometabolic disease, the functional contribution of EETs to adipogenesis and the pathogenesis of obesity remain poorly understood. Our studies demonstrated that induction of adipogenesis in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET levels. Subsequent in vitro experiments demonstrated that exogenous EET analog administration elicits potent anti-adipogenic effects via inhibition of the early phase of adipogenesis. Furthermore, EET analog administration to mice significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro-adipogenic gene expression, and glucose intolerance. Collectively, these findings suggest that suppression of EET bioavailability in adipose tissue is a key pathological consequence of obesity, and strategies that promote the protective effects of EETs in adipose tissue offer enormous therapeutic potential for obesity and its downstream pathological consequences. |
| |
Keywords: | adipose tissue arachidonic acid eicosanoids high-fat diet metabolomics soluble epoxide hydrolase |
本文献已被 ScienceDirect 等数据库收录! |
|