Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids.
Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids.
复制标题
脂联素和相关的 C1q/TNF 相关蛋白选择性地与阴离子磷脂和鞘脂结合。
DOI：
10.1073/pnas.1922270117
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发表时间：
2020
影响因子：
11.1
通讯作者：
Medzhitov,Ruslan
中科院分区：
文献类型：
--
作者：
Ye,JessicaJ;Bian,Xin;Lim,Jaechul;Medzhitov,Ruslan
脂联素（Acrp30）是一种与预防心血管疾病、胰岛素抵抗和炎症相关的脂肪因子。尽管其作用通常归因于结合Adipor1/2和T-cadherin，但其在循环中的丰度、在神经酰胺代谢中的作用以及与C1q的同源性表明，它作为脂质结合蛋白的作用被忽视了，可能可推广到其他C1q/ tnf相关蛋白（CTRPs）和C1q家族成员。为了研究这一点，脂联素、代表性家族成员和变体在Expi293细胞中表达，并使用密度离心检测脂质体与脂质的结合。结合生理脂也被分析使用梯度超离心，液相色谱-质谱，和霰弹枪脂组学。有趣的是，脂联素选择性结合几种阴离子磷脂和鞘脂，包括磷脂酰丝氨酸、神经酰胺-1-磷酸、葡萄糖神经酰胺和硫脂，通过C1q结构域以寡聚依赖的方式结合。在脂质体、低密度脂蛋白、细胞膜和血浆中观察到与脂质的结合。其他CTRPs和C1q家族成员（Cbln1、CTRP1、CTRP5和CTRP13）也结合类似的脂质。这些发现表明脂联素和CTRPs不仅作为激素起作用，而且作为脂质调理素和其他C1q家族蛋白起作用。
Adiponectin (Acrp30) is an adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Although its effects are conventionally attributed to binding Adipor1/2 and T-cadherin, its abundance in circulation, role in ceramide metabolism, and homology to C1q suggest an overlooked role as a lipid-binding protein, possibly generalizable to other C1q/TNF-related proteins (CTRPs) and C1q family members. To investigate this, adiponectin, representative family members, and variants were expressed in Expi293 cells and tested for binding to lipids in liposomes using density centrifugation. Binding to physiological lipids were also analyzed using gradient ultracentrifugation, liquid chromatography-mass spectrometry, and shotgun lipidomics. Interestingly, adiponectin selectively bound several anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, glucosylceramide, and sulfatide, via the C1q domain in an oligomerization-dependent fashion. Binding to lipids was observed in liposomes, low-density lipoproteins, cell membranes, and plasma. Other CTRPs and C1q family members (Cbln1, CTRP1, CTRP5, and CTRP13) also bound similar lipids. These findings suggest that adiponectin and CTRPs function not only as hormones, but also as lipid opsonins, as may other C1q family proteins.