內毒素透過上調cPLA2與COX-2表現改變棕色脂肪組織粒線體生成作用

Lipopolysaccharide modified brown adipose tissue lipolysis and mitogenesis via up-regulation of cPLA2 and COX-2 expression

背景和目的：肥胖是一個全球性的健康問題與各種代謝症候群有關，會受到腸道微生物群改變和脂肪組織組成等因素的影響。本研究目的是探討內毒素(lipopolysaccharide，LPS)如何影響棕色脂肪組織(BAT)在脂解作用和粒線體增生作用中的作用，對於能量消耗和肥胖管理至關重要。方法：實驗中使用雄性C57BL/6小鼠進行高脂飲食(HFD) 餵食，並腹部施打LPS或結合各種抑制劑處理，之後取BAT並評估特定的蛋白質表現。使用的技術包括免疫組織化學染色、即時定量PCR和統計分析。結果：LPS的處理增加BAT中cPLA2和COX-2的表現量，並分別被AG490、BML-275、apocynin或N-acetylcysteine所抑制，說明JAK/STAT、AMPK和NADPH oxidase/ROS參與調控LPS的作用。LPS處理通過減少adipose triglyceride lipase (ATGL)、PAR-γ coactivator-1α (PGC-1α)和uncoupling protein 2 (UCP2)的表現量，影響脂肪分解和粒線體生成作用。抑制cPLA2或COX-2可以逆轉LPS對於脂肪分解與粒線體生成的影響，顯示cPLA2與COX-2在LPS調控BAT功能中的影響。因此，LPS處理可以降低BAT中與代謝功能相關的基因表現導致熱生成效率降低和增加肥胖形成。結論：LPS通過調節cPLA2和COX-2的表現量影響脂肪分解與粒線體含量進而改變BAT的功能。這些發現顯示細菌內毒素和肥胖之間的潛在聯結，針對這些途徑可能提供肥胖處理的新治療策略。

 

Background and purpose: Obesity is a global health issue associated with var-ious metabolic syndromes, influenced by factors including gut microbiota and adi-pose tissue dynamics. This study investigated how lipopolysaccharide (LPS) impair brown adipose tissue (BAT), focusing on its roles in lipolysis and mitogenesis, which are crucial for energy expenditure and obesity management. Methods: In this study, male C57BL/6 mice were fed a high-fat diet (HFD) and treated with LPS alone or LPS combined with various inhibitors to detect the specific proteins in-volved in BAT function. Immunohistochemical staining was used to investigate the changes in protein expression. Results: LPS-upregulated expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in BAT was separately suppressed by AG490, BML-275, apocynin, and N-acetylcysteine, suggesting the participation of JAK, AMPK, and NADPH oxidase/ROS in mediating LPS effects. LPS treatment affected lipolysis and mitogenesis by downregulating the expression of adipose triglyceride lipase, PPAR-γ coactivator-1α, and uncoupling protein 2. In-hibition of cPLA2 or COX-2 reversed the effects of LPS, highlighting their pivotal roles in the LPS-induced reduction of lipolysis and mitogenesis. Thus, LPS treat-ment decreases expression of proteins related to metabolic functions in BAT, con-tributing to suppression of thermogenesis and promotion of obesity. Conclusion: The findings of this study indicate that LPS influences BAT functionality by modu-lating cPLA2 and COX-2 levels, which affects lipolysis and mitochondrial content. These findings highlight a potential association between bacterial endotoxins and obesity, suggesting that targeting these pathways may offer new therapeutic strate-gies for managing obesity.