Department of Medicine, University of Illinois, Chicago, IL 60612, USA.
Department of Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Oct;1866(10):159002. doi: 10.1016/j.bbalip.2021.159002. Epub 2021 Jun 29.
DHA (docosahexaenoic acid) is an essential fatty acid that is required for the normal development and function of the brain. Because of its inability to synthesize adequate amounts of DHA from the precursors, the brain has to acquire DHA from plasma through the blood brain barrier (BBB). Recent studies demonstrated the presence of a transporter at the BBB that specifically transports DHA into the brain in the form of lysophosphatidylcholine (LPC-DHA). However, the mechanism by which LPC-DHA is generated in the plasma is not known. Our previous studies showed that there are at least three different enzymes - lecithin cholesterol acyltransferase (LCAT), endothelial lipase (EL), and hepatic lipase (HL), which can generate LPC-DHA from sn-2 DHA phosphatidylcholine. Here we determined the relative contributions of these enzymes in the delivery of DHA to the brain by measuring the brain DHA levels in the mice deficient in each of these enzymes. The results show that the brain DHA levels of LCAT-deficient mice or EL-deficient mice were not significantly lower than those of their littermates. However, brain DHA was significantly decreased in HL deficient mice (13.5% of total fatty acids) compared to their littermates (17.1%) (p < 0.002), and further decreased to 8.3% of total fatty acids in mice deficient in both HL and EL. These results suggest that HL activity may be the major source for the generation of LPC-DHA in the plasma necessary for transport into the brain, and EL might contribute to this process in the absence of HL.
二十二碳六烯酸（DHA）是一种必需脂肪酸，对于大脑的正常发育和功能至关重要。由于大脑自身无法从前体物中合成足够数量的 DHA，因此必须通过血脑屏障（BBB）从血浆中获取 DHA。最近的研究表明，BBB 上存在一种专门的转运蛋白，可将 DHA 以溶血磷脂酰胆碱（LPC-DHA）的形式转运到大脑中。然而，目前尚不清楚血浆中 LPC-DHA 的生成机制。我们之前的研究表明，至少有三种不同的酶——卵磷脂胆固醇酰基转移酶（LCAT）、内皮脂肪酶（EL）和肝脂肪酶（HL），可以从 sn-2 DHA 磷脂酰胆碱生成 LPC-DHA。在这里，我们通过测量缺乏这些酶的小鼠大脑中的 DHA 水平，来确定这些酶在向大脑输送 DHA 中的相对贡献。结果表明，LCAT 缺乏型或 EL 缺乏型小鼠的大脑 DHA 水平与同窝仔鼠相比并无显著降低。然而，HL 缺乏型小鼠的大脑 DHA 水平明显低于同窝仔鼠（13.5%的总脂肪酸）（p<0.002），而同时缺乏 HL 和 EL 的小鼠则进一步降低至总脂肪酸的 8.3%。这些结果表明，HL 活性可能是血浆中生成必需的 LPC-DHA 的主要来源，而 EL 可能在缺乏 HL 的情况下有助于这一过程。
