Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.