Kayser B D, Lhomme M, Dao M C, Ichou F, Bouillot J-L, Prifti E, Kontush A, Chevallier J-M, Aron-Wisnewsky J, Dugail I, Clément K
Nutriomics Team, Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
Nutriomics Team, INSERM, UMR S U1166, Paris, France.
Int J Obes (Lond). 2017 Jun;41(6):917-925. doi: 10.1038/ijo.2017.63. Epub 2017 Mar 10.
BACKGROUND/OBJECTIVES: Circulating phospholipids and sphingolipids are implicated in obesity-related comorbidities such as insulin resistance and cardiovascular disease. How bariatric surgery affects these important lipid markers is poorly understood. We sought to determine whether Roux-en-Y gastric bypass (RYGB), which is associated with greater metabolic improvement, differentially affects the phosphosphingolipidome compared with adjustable gastric banding (AGB).
SUBJECTS/METHODS: Fasting sera were available from 59 obese women (body mass index range 37-51 kg m; n=37 RYGB and 22 AGB) before surgery, then at 1 (21 RYGB, 12 AGB) and 3 months follow-up (19 RYGB, 12 AGB). HPLC-MS/MS was used to quantify 131 lipids from nine structural classes. DXA measurements and laboratory parameters were also obtained. The associations between lipids and clinical measurements were studied with P-values adjusted for the false discovery rate (FDR).
Both surgical procedures rapidly induced weight loss and improved clinical profiles, with RYGB producing better improvements in fat mass, and serum total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and orosomucoid (FDR <10%). Ninety-three (of 131) lipids were altered by surgery-the majority decreasing-with 29 lipids differentially affected by RYGB during the study period. The differential effect of the surgeries remained statistically significant for 20 of these lipids after adjusting for differences in weight loss between surgery types. The RYGB signature consisted of phosphatidylcholine species not exceeding 36 carbons, and ceramides and sphingomyelins containing C22 to C25 fatty acids. RYGB also led to a sustained increase in unsaturated ceramide and sphingomyelin species. The RYGB-specific lipid changes were associated with decreases in body weight, total and LDL-C, orosomucoid and increased HOMA-S (FDR <10%).
Concomitant with greater metabolic improvement, RYGB induced early and sustained changes in phosphatidylcholines, sphingomyelins and ceramides that were independent of greater weight loss. These data suggest that RYGB may specifically alter sphingolipid metabolism, which, in part, could explain the better metabolic outcomes of this surgical procedure.
背景/目的：循环中的磷脂和鞘脂与肥胖相关的合并症有关，如胰岛素抵抗和心血管疾病。减肥手术如何影响这些重要的脂质标志物，目前尚不清楚。我们试图确定与更好的代谢改善相关的 Roux-en-Y 胃旁路术（RYGB）与可调节胃束带术（AGB）相比，是否对磷酸鞘脂组有不同的影响。
受试者/方法：收集了 59 名肥胖女性（体重指数范围为 37 - 51 kg/m²；37 例行 RYGB，22 例行 AGB）术前、术后 1 个月（21 例行 RYGB，12 例行 AGB）和 3 个月随访（19 例行 RYGB，12 例行 AGB）时的空腹血清。采用高效液相色谱-串联质谱法（HPLC-MS/MS）对 9 种结构类别的 131 种脂质进行定量分析。还进行了双能 X 线吸收测定（DXA）和实验室参数检测。通过对错误发现率（FDR）进行校正的 P 值研究脂质与临床测量值之间的关联。
两种手术均迅速导致体重减轻并改善临床指标，RYGB 在减少脂肪量、血清总胆固醇、低密度脂蛋白胆固醇（LDL-C）和血清类黏蛋白方面改善更明显（FDR < 10%）。手术改变了 131 种脂质中的 93 种（大多数脂质减少），在研究期间有 29 种脂质受到 RYGB 的不同影响。在调整手术类型之间体重减轻的差异后，其中 20 种脂质的手术差异效应仍具有统计学意义。RYGB 的特征性脂质包括碳数不超过 36 的磷脂酰胆碱种类，以及含有 C22 至 C25 脂肪酸的神经酰胺和鞘磷脂。RYGB 还导致不饱和神经酰胺和鞘磷脂种类持续增加。RYGB 特异性的脂质变化与体重、总胆固醇和 LDL-C、血清类黏蛋白的降低以及胰岛素抵抗稳态模型评估（HOMA-S）的增加相关（FDR < 10%）。
与更好的代谢改善同时出现的是，RYGB 诱导了磷脂酰胆碱、鞘磷脂和神经酰胺的早期和持续变化，这些变化独立于更大程度的体重减轻。这些数据表明，RYGB 可能特异性地改变鞘脂代谢，这在一定程度上可以解释该手术更好的代谢效果。
