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.

脂联素 (Acrp30) 是一种脂肪因子，与预防心血管疾病、胰岛素抵抗和炎症有关。尽管其作用通常归因于结合 Adipor1/2 和 T-钙粘蛋白，但其在循环中的丰度、在神经酰胺代谢中的作用以及与 C1q 的同源性表明其作为脂质结合蛋白的作用被忽视，可能可推广到其他 C1q/TNF 相关蛋白蛋白 (CTRP) 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，并使用密度离心测试与脂质体中脂质的结合。还使用梯度超速离心、液相色谱-质谱法和鸟枪脂质组学分析了与生理脂质的结合。有趣的是，脂联素通过 C1q 结构域以寡聚依赖性方式选择性结合多种阴离子磷脂和鞘脂，包括磷脂酰丝氨酸、1-磷酸神经酰胺、葡萄糖神经酰胺和脑硫脂。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 CTRP 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 CTRP 不仅充当激素，而且还充当脂质调理素，就像其他 C1q 家族蛋白一样。