Institut de recheches cliniques de Montréal (IRCM), Montréal, Québec, Canada.
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2785-93. doi: 10.1161/ATVBAHA.112.300306. Epub 2012 Sep 20.
White adipose tissue (WAT) dysfunction is characterized by delayed clearance of dietary triglyceride-rich lipoproteins (TRL). We reported that apolipoprotein (apo) C-I, a transferable apolipoprotein that inhibits lipoprotein lipase activity when bound to TRL, was produced by a human adipocyte model. Thus, we aimed to determine whether increased WAT apoC-I secretion is related to delayed dietary fat clearance in humans.
After the ingestion of a (13)C-triolein-labeled high-fat meal, postmenopausal obese women with high-fasting WAT apoC-I secretion (median >0.81 μmol/L per g/4 hours, n=9) had delayed postprandial plasma clearance of (13)C-triglyceride and (13)C-nonesterified fatty acids over 6 hours compared with controls. WAT apoC-I secretion over 4 hours correlated with fasting total and non-high-density lipoprotein apoC-I but not with high-density lipoprotein apoC-I and was the primary predictor of 4-hour postprandial increases in TRL apoC-I. Correction for TRL apoC-I eliminated the association of WAT apoC-I with 6-hour area under the curve of plasma (13)C-triglyceride; correction for insulin sensitivity or inflammation did not. Finally, in addition to apoC-I, WAT secreted considerable amount of apoC-II, apoC-III, and apoE over 24 hours; however, only WAT apoC-I secretion was associated with 6-hour area under the curve of plasma (13)C-triglyceride.
Increased WAT apoC-I secretion in obese women is associated with delayed postprandial dietary fat clearance mediated by increased TRL apoC-I. Thus, we hypothesize that reducing WAT apoC-I secretion ameliorates WAT dysfunction and associated cardiometabolic risks in humans.
白色脂肪组织（WAT）功能障碍的特征是膳食甘油三酯丰富的脂蛋白（TRL）的清除延迟。我们报道载脂蛋白（apo）C-I 是一种可转移的载脂蛋白，当与 TRL 结合时会抑制脂蛋白脂肪酶的活性，它是由人类脂肪细胞模型产生的。因此，我们旨在确定增加的 WAT apoC-I 分泌是否与人类膳食脂肪清除延迟有关。
在摄入（13）C-三油酸甘油酯标记的高脂肪餐后，绝经后肥胖女性的空腹 WAT apoC-I 分泌量较高（中位数>0.81 μmol/L 每 g/4 小时，n=9），与对照组相比，餐后 6 小时内血浆（13）C-甘油三酯和（13）C-非酯化脂肪酸的清除延迟。4 小时内 WAT apoC-I 分泌与空腹总和非高密度脂蛋白 apoC-I 相关，但与高密度脂蛋白 apoC-I 无关，是 TRL apoC-I 餐后 4 小时增加的主要预测因素。校正 TRL apoC-I 消除了 WAT apoC-I 与 6 小时血浆（13）C-甘油三酯曲线下面积的关联；校正胰岛素敏感性或炎症并没有消除这种关联。最后，除了 apoC-I，WAT 在 24 小时内还分泌了相当数量的 apoC-II、apoC-III 和 apoE；然而，只有 WAT apoC-I 分泌与血浆（13）C-甘油三酯的 6 小时曲线下面积相关。
肥胖女性 WAT apoC-I 分泌增加与通过增加 TRL apoC-I 介导的餐后膳食脂肪清除延迟有关。因此，我们假设减少 WAT apoC-I 分泌可以改善人类 WAT 功能障碍和相关的心血管代谢风险。
