Wassef Hanny, Bissonnette Simon, Dufour Robert, Davignon Jean, Faraj May
Montreal Clinical Research Institute, Montreal, Quebec, Canada.
Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; and.
J Nutr. 2017 May;147(5):754-762. doi: 10.3945/jn.116.242750. Epub 2017 Mar 29.
The role of plasma apolipoprotein (apo) C-I in cardiometabolic risk in humans is unclear. However, in vitro studies showed a dual role for apoC-I, both protective and harmful, depending on the carrier lipoprotein. We tested the hypothesis that triglyceride (TG)-rich lipoprotein (TRL) apoC-I, not total or HDL apoC-I, is associated with delayed postprandial plasma clearance of TRLs, independently of apoC-II, apoC-III, and apoE. This cross-sectional study examines the plasma clearance of a C-triolein-labeled high-fat meal (68% fat energy) in 20 postmenopausal overweight and obese women [body mass index (in kg/m) ≥27; aged 45-74 y] as the increment change in area under the 6-h postprandial curves (iAUC) of TRL parameters. Lipoproteins were fractionated by fast-protein LC. Transferable apolipoproteins were measured by ELISA. TRL enrichment with apolipoproteins was calculated by dividing their TRL concentrations by TRL apoB. The effects of human apoC-I and apoC-III on the hydrolysis and storage of H-triolein-labeled TRLs were tested in 3T3-L1 adipocytes. TRL apoC-I was positively associated with plasma apo B-48 and total and non-HDL TGs, cholesterol, and apoB ( = 0.52-0.97) and negatively with HDL cholesterol ( = -0.52) and LDL diameter ( = -0.91) ( < 0.05). Total and HDL apoC-I were correlated only with total ( = 0.62) and HDL ( = 0.75) cholesterol. Women with high fasting TRL enrichment with apoC-I (99-365 μmol apoC-I/μmol apoB), but not apoC-II, apoC-III, or apoE, had higher iAUC for TGs (+195%), C-TGs (+319%), and apo B-48 (+186%) than those with low enrichment (14-97 μmol apoC-I/μmol apoB). The 4-h postprandial increase in TRL apoC-I was associated with a 4-h increase in TRL TGs and iAUC for TGs, C-TGs, and apo B-48 ( = 0.74-0.86, < 0.001), independently of 4-h changes in TRL apoB, apoC-II, apoC-III, or apoE. ApoC-I and apoC-III inhibited H-TRL clearance by adipocytes by >75% ( < 0.001). TRL enrichment with apoC-I is positively associated with postprandial hypertriglyceridemia and remnant accumulation in postmenopausal overweight and obese women, independently of apoC-II, apoC-III, or apoE, which may be due to inhibiting TRL clearance by adipocytes. Reducing TRL apoC-I may ameliorate delayed postprandial plasma clearance of TRLs and associated risks in humans.
血浆载脂蛋白（apo）C-I在人类心脏代谢风险中的作用尚不清楚。然而，体外研究表明apoC-I具有双重作用，根据载体脂蛋白的不同，既具有保护作用又具有有害作用。我们检验了这样一个假设：富含甘油三酯（TG）的脂蛋白（TRL）中的apoC-I，而非总apoC-I或高密度脂蛋白（HDL）中的apoC-I，与TRL餐后血浆清除延迟相关，且独立于apoC-II、apoC-III和载脂蛋白E（apoE）。这项横断面研究检测了20名绝经后超重和肥胖女性[体重指数（kg/m²）≥27；年龄45 - 74岁]摄入C-三油酸甘油酯标记的高脂餐（脂肪能量占68%）后的血浆清除情况，以TRL参数餐后6小时曲线下面积（iAUC）的增量变化来衡量。脂蛋白通过快速蛋白液相色谱法进行分离。可转移载脂蛋白通过酶联免疫吸附测定法（ELISA）进行检测。通过将载脂蛋白的TRL浓度除以TRL载脂蛋白B（apoB）来计算载脂蛋白在TRL中的富集情况。在3T3-L1脂肪细胞中测试了人apoC-I和apoC-III对H-三油酸甘油酯标记的TRL水解和储存的影响。TRL中的apoC-I与血浆载脂蛋白B-48、总TG和非HDL TG、胆固醇及apoB呈正相关（r = 0.52 - 0.97），与HDL胆固醇呈负相关（r = -0.52），与低密度脂蛋白（LDL）直径呈负相关（r = -0.91）（P < 0.05）。总apoC-I和HDL中的apoC-I仅分别与总胆固醇（r = 0.62）和HDL胆固醇（r = 0.75）相关。空腹时apoC-I在TRL中富集程度高（99 - 365 μmol apoC-I/μmol apoB）的女性，而非apoC-II、apoC-III或apoE富集程度高的女性，其TG的iAUC（增加195%）、C-TG的iAUC（增加319%）和apo B-48的iAUC（增加186%）均高于富集程度低（14 - 97 μmol apoC-I/μmol apoB）的女性。餐后TRL中apoC-I在4小时内的增加与TRL TG在4小时内的增加以及TG、C-TG和apo B-48的iAUC相关（r = 0.74 - 0.86，P < 0.001），且独立于TRL apoB、apoC-II、apoC-III或apoE在4小时内的变化。apoC-I和apoC-III使脂肪细胞对H-TRL的清除率降低超过75%（P < 0.001）。在绝经后超重和肥胖女性中，TRL中apoC-I的富集与餐后高甘油三酯血症和残余颗粒蓄积呈正相关，且独立于apoC-II、apoC-III或apoE，这可能是由于其抑制了脂肪细胞对TRL的清除。降低TRL中的apoC-I可能会改善人类餐后TRL血浆清除延迟及相关风险。
