The early effects of sleeve gastrectomy on postprandial chylomicron triglycerides during the progression of type 2 diabetes.

[Display omitted] • Acute sleeve gastrectomy (SG) improves postprandial chylomicron, not VLDL triglycerides (TGs). • Type 2 diabetes (DM) patients after SG show less improvement in postprandial chylomicron TGs than patients without DM. • Postprandial chylomicron metabolites in DM patients after SG increase intestinal cell fatty acid synthesis. • The timing for SG to improve postprandial chylomicron TGs and the potential risk of cardiovascular disease is before DM. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]