ELOVL6於3T3-L1脂肪細胞中對脂多醣誘導發炎反應之調控作用

Abstract

第二型糖尿病 (type 2 diabetes, T2D) 以胰島素阻抗為主要特徵，其中脂肪組織發炎扮演關鍵角色。ELOVL6 為參與脂質代謝之脂肪酸延長酶，可透過調控脂肪酸組成影響代謝穩態。本研究利用 3T3-L1 細胞模型，探討 ELOVL6 抑制 (knockdown, KD) 是否依脂肪細胞分化階段不同而調控發炎相關基因表現。於脂多醣 (lipopolysaccharide, LPS) 刺激下，ELOVL6 KD 在早期脂肪細胞中降低 Tnf 與 Il6 表現，並增加 Ccl2 表現；然而在成熟脂肪細胞中，則觀察到 Tnf 與 Il6 表現有上升趨勢、Ccl2 表現有下降趨勢，且脂質累積未出現 ELOVL6 KD 依賴性之顯著改變，顯示 ELOVL6 對發炎反應的影響可能受到脂肪細胞分化階段所影響。此結果顯示 ELOVL6 對發炎反應的調控可能具有分化階段依賴性(differentiation-stage-dependent)，而非單純地抑制或促進發炎反應。其機制可能與脂肪酸組成改變所導致之脂質重塑有關，進而影響膜相關訊號傳遞與壓力反應途徑。整體而言，本研究顯示，在總脂質累積量未明顯改變的情況下，ELOVL6 KD 仍可能影響發炎相關基因表現，提示脂質組成或脂質重塑可能參與脂肪細胞發炎反應的調控。然而，此機制仍需進一步透過脂質體學分析加以驗證。

Type 2 diabetes (T2D) is characterized by insulin resistance, in which adipose tissue inflammation plays a key role. ELOVL6, a fatty acid elongase, regulates lipid composition and has been implicated in metabolic homeostasis, although its role in inflammation remains unclear. This study used a 3T3-L1 adipocyte differentiation model to examine whether ELOVL6 knockdown (KD) differentially affects inflammation-associated gene expression at different stages of adipocyte differentiation. Following lipopolysaccharide (LPS) stimulation, ELOVL6 KD reduced Tnf and Il6 expression but increased Ccl2 expression in early-stage adipocytes. In contrast, in mature adipocytes, ELOVL6 KD showed a tendency toward increased Tnf and Il6 expression and reduced Ccl2 expression, while not significantly affecting lipid accumulation. These findings suggest that ELOVL6 knockdown may influence inflammatory gene expression in a differentiation-stage-dependent manner. Since lipid accumulation was not significantly altered, the observed changes in inflammatory gene expression may be related to lipid remodeling rather than total lipid quantity; however, this mechanism requires further validation by lipidomic analysis.