背景:目前尚不清楚早期袖状胃切除术(SG)是否以与体重无关的方式改善2型糖尿病(DM)患者的餐后极低密度脂蛋白(VLDL)和乳糜微粒甘油三酯(TG)。本文研究了SG对餐后VLDL和乳糜微粒动力学的早期影响。
方法:在SG的1周之前和之后进行液体膳食测试。收集血浆用于餐后富含甘油三酯的脂蛋白动力学分析,包括VLDLs和乳糜微粒,通过高速超速离心分离。脂质组学和代谢组学用于描述血浆和餐后乳糜微粒的脂质和代谢物组成。使用RT-PCR检查用乳糜微粒代谢物处理的肠上皮细胞中的从头脂肪酸合成,免疫印迹,和游离脂肪酸测量。
结果:我们发现DM患者的VLDLTG明显高于非DM患者,在SG之后,这种增加仍然保留。相比之下,SG显著降低餐后乳糜微粒TG,但令人惊讶的是,DM患者的减少程度不如无DM患者明显,通过非靶向脂质组学分析证实。此外,通过对接受SG的DM患者的餐后乳糜微粒进行进一步的代谢组学分析,发现了5种可能与通路分析的从头脂肪酸合成相关的独特代谢物,并通过体外肠上皮细胞培养实验进行了验证。
结论:SG在1周内不影响餐后VLDL,但乳糜微粒TG降低。DM患者在SG后保持较高的餐后乳糜微粒TG浓度,可能通过一些增加肠道脂肪酸合成的独特代谢产物。这些结果暗示SG达到较低的肠脂肪酸合成和餐后乳糜微粒TG产生的时机在DM诊断之前可能会降低心血管风险。
BACKGROUND: It remains unclear whether early sleeve gastrectomy (SG) improves postprandial very-low-density lipoprotein (VLDL) as well as chylomicron triglycerides (TGs) in a weight-independent manner in patients with or without type 2 diabetes (DM). Herein we investigated the early effects of SG on postprandial VLDL and chylomicron kinetics.
METHODS: A liquid meal test was performed before and after 1 week of SG. The plasma was collected for postprandial triglyceride-rich lipoprotein kinetics analyses, including VLDLs and
chylomicrons, isolated by high-speed ultracentrifugation. Lipidomics and metabolomics were used to profile lipid and metabolite compositions of plasma and postprandial
chylomicrons. De novo fatty acid synthesis in intestinal epithelial cells treated with chylomicron metabolites was examined using RT-PCR, immunoblotting, and free fatty acid measurement.
RESULTS: We found that patients with DM had markedly higher VLDL TGs than patients without DM, and such an increase was still retained after SG. In contrast, SG significantly decreased postprandial chylomicron TGs, but surprisingly, the degree of the reduction in patients with DM was less prominent than in patients without DM, confirmed by untargeted lipidomics analysis. Moreover, 5 unique metabolites potentially linked to de novo fatty acid synthesis from the pathway analysis were discovered by further metabolomic analysis of postprandial
chylomicrons from patients with DM who underwent SG and verified by In vitro intestinal epithelial cell culture experiments.
CONCLUSIONS: SG in 1 week did not impact postprandial VLDL but decreased chylomicron TGs. Patients with DM keep higher postprandial chylomicron TG concentrations than patients without it after SG, potentially through some unique metabolites that increase intestinal fatty acid synthesis. These results implicate the timing for SG to reach lower intestinal fatty acid synthesis and postprandial chylomicron TG production is prior to the diagnosis of DM to potentially reduce cardiovascular risks.