脂联素是脂肪细胞分泌的丰富的脂肪细胞因子。它以三聚体、六聚体、高分子量 (HMW) 和球状（蛋白水解产物）亚型存在于血浆中。脂联素对巨噬细胞的抗炎作用仍存在争议。我们之前报道了一种从人血浆中纯化天然 HMW 脂联素的简单有效的方法。在这里，我们研究了人血浆中的天然 HMW 脂联素是否对巨噬细胞具有抗炎作用。用人天然 HMW 脂联素预处理可抑制脂多糖 (LPS) 诱导的白细胞介素 1β (IL-1β) 基因表达，但不抑制肿瘤坏死因子 (TNF)-α 表达。然而，同时用 HMW 脂联素和 LPS 处理并不能抑制 IL-1β 的表达。此外，HMW 脂联素预处理通过消除 LPS 诱导的 Akt (Ser473) 磷酸化来减少糖原合酶激酶 3β (GSK-3β) 失活，从而抑制 LPS 诱导的 CCAAT/增强子结合蛋白 β (C/EBPβ) 蛋白翻译和核转位。然而，HMW 脂联素预处理并不影响 LPS 诱导的核因子-κB (NF-κB) 激活。这些结果表明，HMW 脂联素通过抑制其 Akt-C/EBPβ 信号通路，从而抑制 IL-1β 基因表达，从而在巨噬细胞中介导有效的抗炎活性。

Adiponectin is an abundant adipocytokine secreted by adipocytes. It exists in the plasma in its trimeric, hexameric, high-molecular-weight (HMW), and globular (a proteolytic product) isoforms. Adiponectin's anti-inflammatory effects on macrophages remain controversial. We have previously reported a simple and effective method for purifying native HMW adiponectin from human plasma. Here, we investigated whether native HMW adiponectin from human plasma has anti-inflammatory effects on macrophages. Pretreatment with human native HMW adiponectin inhibited lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) gene expression, but not tumor necrosis factor (TNF)-α expression. However, simultaneous treatment with HMW adiponectin and LPS did not inhibit IL-1β expression. Further, HMW adiponectin pretreatment decreases glycogen synthase kinase-3β (GSK-3β) inactivation by abrogating LPS-induced Akt (Ser473) phosphorylation, which subsequently suppresses LPS-induced CCAAT/enhancer binding protein β (C/EBPβ) protein translation and nuclear translocation. However, HMW adiponectin pretreatment did not affect LPS-induced nuclear factor-kappaB (NF-κB) activation. These results suggest that HMW adiponectin mediates potent anti-inflammatory activities in macrophages by inhibiting its Akt-C/EBPβ signaling pathway, thereby suppressing IL-1β gene expression.