RESULTS: We found that ISO and LPS stimulated lipolysis at comparable intensities. Exposure to either treatment tended to elevate the release of eCBs and NAEs by cultured adipocytes; however, specific eCBs and NAEs and the transcriptional profiles differed by treatment. On one hand, ISO enhanced adipocytes\' release of 2-arachidonoylglycerol (2-AG) but reduced NAE production. Notably, ISO enhanced the cells\' expression of enzymes associated with 2-AG biosynthesis (INPP5F, GDPD5, GPAT4), transport (CD36), and adipogenesis (PPARG). Conversely, LPS enhanced adipocytes\' synthesis and release of N-arachidonoylethanolamide (AEA). This change coincided with enhanced transcription of the NAE-biosynthesizing enzyme, PTPN22, and adipocytes\' transcription of genes related to eCB degradation (PTGS2, MGLL, CYP27B1). Furthermore, LPS enhanced adipocytes\' transcription of eCB and NAE transporters (HSPA1A, SCP2) and the expression of the anti-adipogenic ion channel, TRPV3.
CONCLUSIONS: Our data provide evidence for distinct modulatory roles of canonical and inflammatory lipolysis pathways over eCB release and transcriptional regulation of biosynthesis, degradation, transport, and ECS signaling in cows\' adipocytes. Based on our findings, we conclude that, within adipocytes, eCB production and ECS component expression are, at least in part, mediated by lipolysis in a pathway-dependent manner. These findings contribute to a deeper understanding of the molecular mechanisms underlying metabolic regulation in dairy cows\' AT, with potential implications for prevention and treatment of inflammatory and metabolic disorders.
结果:我们发现ISO和LPS以相当的强度刺激脂解。暴露于任何一种治疗都倾向于提高培养的脂肪细胞的eCB和NAE的释放;然而,特定的eCB和NAE以及转录谱因治疗而异。一方面,ISO增强脂肪细胞释放2-花生四酰基甘油(2-AG)但减少NAE产生。值得注意的是,ISO增强了与2-AG生物合成相关的酶的细胞表达(INPP5F,GDPD5,GPAT4),运输(CD36),和脂肪生成(PPARG)。相反,LPS增强脂肪细胞合成和N-花生四烯酸乙醇胺(AEA)的释放。这种变化与NAE生物合成酶的转录增强相吻合,PTPN22和脂肪细胞转录与eCB降解相关的基因(PTGS2,MGLL,CYP27B1)。此外,LPS增强脂肪细胞eCB和NAE转运蛋白的转录(HSPA1A,SCP2)和抗脂肪离子通道的表达,TRPV3.
结论:我们的数据为规范和炎症脂解途径对eCB释放和生物合成转录调节的不同调节作用提供了证据,降解,运输,和ECS信号在奶牛脂肪细胞中的作用。根据我们的发现,我们的结论是,在脂肪细胞内,eCB生产和ECS组件表达式是,至少在某种程度上,脂解以途径依赖性方式介导。这些发现有助于更深入地了解奶牛AT代谢调节的分子机制,对炎症和代谢紊乱的预防和治疗有潜在的影响。