Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Surg Obes Relat Dis. 2013 Jan-Feb;9(1):100-7. doi: 10.1016/j.soard.2011.11.018. Epub 2011 Dec 20.
Obesity-associated hyperlipidemia and hyperlipoproteinemia are risk factors for cardiovascular disease (CVD). Recently, ceramide-derived sphingolipids were identified as a novel independent CVD risk factor. We hypothesized that the beneficial effect of Roux-en-Y gastric bypass (RYGB) on CVD risk is related to ceramide-mediated improvement in lipoprotein profile.
A prospective study of patients undergoing RYGB was conducted. The patients' clinical data and biochemical markers related to cardiovascular risk were documented. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1), apolipoprotein (Apo)B100 and ApoA1 were quantified preoperatively and 3 and 6 months after RYGB, as was the Framingham risk score. Brachial artery reactivity testing was performed before and 6 months after RYGB.
Ten patients (9 women; age 48.6 ± 9.6 yr; body mass index, 48.5 ± 5.8 kg/m(2)) were included in the present study. At 6 months postoperatively, the mean body mass index had decreased to 35.7 ± 5.0 kg/m(2), corresponding to 51.3% ± 10.0% excess weight loss. The fasting total cholesterol, triglycerides, low-density lipoprotein, free fatty acids, ApoB100, ApoB100/ApoA1 ratio and insulin resistance estimated from Homeostasis Model of Assessment of Insulin Resistance were significantly reduced compared with the preoperative values. The ApoB100/ApoA1 ratio correlated with a reduction in ceramide subspecies (C18:0, C18:1, C20:0, C24:0, and C24:1; P < .05). ApoB100 and the ApoB100/ApoA1 ratio also correlated positively with the reduction in triglycerides, low-density lipoprotein, and Homeostasis Model of Assessment of Insulin Resistance (P < .05). Brachial artery reactivity testing correlated inversely with ApoB100 and total ceramide (P = .05). Furthermore, the change in brachial artery reactivity testing correlated with the decrease in C16:0 (P < .03).
Our data suggest that improvements in lipid profiles and CVD risk factors after gastric bypass surgery could be linked to changes in ceramide lipids. Mechanistic studies are needed to determine whether this link is causative or purely correlative.
肥胖相关的高脂血症和高脂蛋白血症是心血管疾病(CVD)的危险因素。最近,神经酰胺衍生的鞘脂被确定为 CVD 的一个新的独立危险因素。我们假设 Roux-en-Y 胃旁路(RYGB)对 CVD 风险的有益作用与神经酰胺介导的脂蛋白谱改善有关。
对接受 RYGB 的患者进行前瞻性研究。记录患者的临床数据和与心血管风险相关的生化标志物。术前和 RYGB 后 3 个月和 6 个月检测血浆神经酰胺亚种(C14:0、C16:0、C18:0、C18:1、C20:0、C24:0 和 C24:1)、载脂蛋白(Apo)B100 和 ApoA1,并计算 Framingham 风险评分。在 RYGB 前后进行肱动脉反应性测试。
本研究纳入 10 例患者(9 例女性;年龄 48.6 ± 9.6 岁;体重指数 48.5 ± 5.8 kg/m2)。术后 6 个月,平均体重指数下降至 35.7 ± 5.0 kg/m2,相当于 51.3% ± 10.0%的超重减轻。空腹总胆固醇、甘油三酯、低密度脂蛋白、游离脂肪酸、ApoB100、ApoB100/ApoA1 比值和稳态模型评估的胰岛素抵抗均显著低于术前值。ApoB100/ApoA1 比值与神经酰胺亚种(C18:0、C18:1、C20:0、C24:0 和 C24:1)的减少呈正相关(P <.05)。ApoB100 和 ApoB100/ApoA1 比值也与甘油三酯、低密度脂蛋白和稳态模型评估的胰岛素抵抗的降低呈正相关(P <.05)。肱动脉反应性测试与 ApoB100 和总神经酰胺呈负相关(P =.05)。此外,肱动脉反应性测试的变化与 C16:0 的减少呈正相关(P <.03)。
我们的数据表明,胃旁路手术后血脂谱和 CVD 危险因素的改善可能与神经酰胺脂质的变化有关。需要进行机制研究以确定这种联系是因果关系还是纯粹的相关性。