细胞色素 P450 加单氧酶衍生的 EPA 和 DHA 氧化产物 17,18-环氧二十碳四烯酸和 19,20-环氧二十二碳五烯酸通过 GPR120-AMPKα 信号通路促进 BAT 产热和 WAT 褐变。
Cytochrome P450 epoxygenase-derived EPA and DHA oxylipins 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid promote BAT thermogenesis and WAT browning through the GPR120-AMPKα signaling pathway.
机构信息
Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China.
National Engineering Research Center for Breeding Swine Industry and UBT Lipid Suite Functional Fatty Acids Research Center, South China Agricultural University, Guangzhou 510642, P. R. China.
出版信息
Food Funct. 2022 Feb 7;13(3):1232-1245. doi: 10.1039/d1fo02608a.
The mechanisms whereby fish oil rich in EPA and DHA promotes BAT thermogenesis and WAT browning are not fully understood. Thus, this study aimed to investigate the effects of cytochrome P450 (CYP) epoxygenase-derived EPA and DHA oxylipins 17,18-EpETE and 19,20-EpDPE on BAT thermogenesis and WAT browning and explore the underlying mechanism. Stromal vascular cells (SVCs) were subjected to 17,18-EpETE or 19,20-EpDPE treatment and mice were treated with the CYP epoxygenase inhibitor, the thermogenic marker genes were detected and the involvement of GPR120 and AMPKα were assessed. The results indicated that 17,18-EpETE and 19,20-EpDPE induced brown and beige adipocyte thermogenesis, with increased expression of thermogenic marker gene UCP1 in differentiated SVCs. Meanwhile, the expression of GPR120 and phosphorylation of AMPKα were increased in response to these two oxylipins. However, the inhibition of GPR120 and AMPKα inhibited the promotion of adipocyte thermogenesis. In addition, in the presence of CYP epoxygenase inhibitor MS-PPOH, EPA and DHA had no effect on increasing UCP1 expression in differentiated SVCs. Consistent with the results, the findings demonstrated that fish oil had no body fat-lowering effects and no effects on enhancing energy metabolism, iBAT thermogenesis and iWAT browning in mice fed HFD after intraperitoneal injection of CYP epoxygenase inhibitor SKF-525A. Moreover, fish oil had no effect on the elevation of GPR120 expression and activation of AMPKα in iBAT and iWAT in mice fed HFD after intraperitoneal injection of SKF-525A. In summary, our results showed that CYP epoxygenase-derived EPA and DHA oxylipins 17,18-EpETE and 19,20-EpDPE promoted BAT thermogenesis and WAT browning through the GPR120-AMPKα signaling pathway, which might contribute to the thermogenic and anti-obesity effects of fish oil.
富含 EPA 和 DHA 的鱼油促进 BAT 产热和 WAT 棕色化的机制尚不完全清楚。因此，本研究旨在探讨细胞色素 P450（CYP）环氧合酶衍生的 EPA 和 DHA 氧代脂质 17,18-EpETE 和 19,20-EpDPE 对 BAT 产热和 WAT 棕色化的影响，并探讨其潜在机制。基质血管细胞（SVCs）接受 17,18-EpETE 或 19,20-EpDPE 处理，并用 CYP 环氧合酶抑制剂处理小鼠，检测热生成标记基因，并评估 GPR120 和 AMPKα 的参与。结果表明，17,18-EpETE 和 19,20-EpDPE 诱导棕色和米色脂肪细胞产热，分化的 SVCs 中 UCP1 表达增加。同时，两种氧代脂质均增加了 GPR120 的表达和 AMPKα 的磷酸化。然而，GPR120 和 AMPKα 的抑制抑制了脂肪细胞产热的促进。此外，在存在 CYP 环氧合酶抑制剂 MS-PPOH 的情况下，EPA 和 DHA 对增加分化的 SVCs 中 UCP1 的表达没有影响。与结果一致，研究结果表明，在腹腔注射 CYP 环氧合酶抑制剂 SKF-525A 后，鱼油对 HFD 喂养的小鼠没有降低体脂肪和增强能量代谢、iBAT 产热和 iWAT 棕色化的作用。此外，在腹腔注射 SKF-525A 后，鱼油对 HFD 喂养的小鼠 iBAT 和 iWAT 中 GPR120 表达的升高和 AMPKα 的激活没有影响。综上所述，我们的结果表明，CYP 环氧合酶衍生的 EPA 和 DHA 氧代脂质 17,18-EpETE 和 19,20-EpDPE 通过 GPR120-AMPKα 信号通路促进 BAT 产热和 WAT 棕色化，这可能有助于鱼油的产热和抗肥胖作用。
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