| 摘要: | 賽滅寧（cypermethrin, CYP）為一種作用於神經系統的合成除蟲菊精類殺蟲劑，廣泛應用在農業及家庭殺蟲劑使用。本研究探討攝食一般飲食或高脂飲食合併暴露低劑量的CYP，對於雄性小鼠體內脂肪生成以及肝臟代謝之影響。雄性C57BL/6J小鼠分別餵食AIN-93M飼料和高脂飼料（脂肪佔總熱量50%），代表一般飲食和高脂飲食。一般飲食除了正常對照（NC）組，另有三組CYP暴露組，分別為CYP低劑量（CL）組、CYP中劑量（CM）組及CYP高劑量（CH）組，餵食添加CYP的AIN-93M飼料（CYP暴露劑量分別為: 1、2.5及5 mg/kg B.W./day）；而高脂飲食除了高脂對照（HF）組外，另有高脂合併CYP暴露（HFC）組，餵食添加CYP的高脂飼料（CYP暴露劑量: 5 mg/kg B.W./day）。實驗進行60天飼料介入後犧牲所有小鼠，收集血液、肝臟、副睪脂肪及盲腸內容物進行分析。實驗結果顯示，與NC組相比，CH組小鼠副睪脂肪重量增加，血漿總膽固醇相關指標上升，血液促發炎單核球減少，副睪脂肪和肝臟中M1巨噬細胞比例的增加；此外，副睪脂肪的diglyceride acyltransferase (DGAT）1、interleukin-18、plasminogen activator inhibitor-I、adiponectin和leptin基因表現量增加，而肝臟中DGAT2、hydroxymethylglutaryl-CoA reductase、chemokine (C-C motif) ligand 2和TNF receptor superfamily member 6（Fas）的基因表現量亦提升；盲腸的SCFA濃度不受影響，厭氧桿菌屬（Anaerobacterium）為優勢菌種。與HF組相比，HFC組小鼠血漿TG與睪固酮含量提升，副睪脂肪的DGAT2和leptin基因表現量增加，肝臟中DGAT2、aldolase C、lipopolysaccharide binding protein和Fas基因表現量上升，盲腸中乙酸減少而丁酸增加，且丁酸生成的菌種為優勢菌種。本研究結果顯示，雄性C57BL/6J小鼠無論給予一般飲食或高脂飲食，合併低劑量CYP暴露對於體重皆無顯著影響，然而卻會提升血脂濃度，並促進副睪脂肪和肝臟組織中脂肪合成相關基因的表現量，可能會增加肥胖和血脂代謝異常相關慢性病之風險。
Cypermethrin (CYP) is a synthetic pyrethroid insecticide that acts on the nervous system and is widely used in agriculture and household insecticides. This study investigates the effects of low-dose CYP exposure from a normal diet or a high-fat diet on lipogenesis and liver metabolism in male mice. Male C57BL/6J mice were fed either AIN-93M diet or a high-fat diet (with fat accounting for 50% of total calories), representing the normal diet and high-fat diet, respectively. In addition to the normal control (NC) group, the normal diet had three CYP exposure groups: CYP low-dose (CL), CYP medium-dose (CM), and CYP high-dose (CH), fed with AIN-93M diet containing CYP (CYP exposure doses: 1, 2.5, and 5 mg/kg B.W./day, respectively). The high-fat diet included a high-fat control (HF) group and a high-fat diet combined with CYP exposure (HFC) group, fed with a high-fat diet containing CYP (CYP exposure dose: 5 mg/kg B.W./day). After 60 days of dietary intervention, all mice were sacrificed, and blood, liver, epididymal fat, and cecal contents were collected for analysis. The results showed that, compared to the NC group, the CH group mice had increased epididymal fat weight, elevated plasma total cholesterol-related indicators, reduced pro-inflammatory monocytes in the blood, and increased M1 macrophage proportions in epididymal fat and liver. Additionally, in the epididymal fat, the gene expressions of diglyceride acyltransferase (DGAT) 1, interleukin-18, plasminogen activator inhibitor-I, adiponectin, and leptin were increased, while in the liver, the gene expressions of DGAT2, hydroxymethylglutaryl-CoA reductase, chemokine (C-C motif) ligand 2, and TNF receptor superfamily member 6 (Fas) were also elevated. The SCFA concentration in the cecum was not affected, and the dominant strain is Anaerobacterium. Compared to the HF group, the HFC group mice had increased plasma TG and testosterone levels, higher gene expressions of DGAT2 and leptin in the epididymal fat, and elevated gene expressions of DGAT2, aldolase C, lipopolysaccharide binding protein, and Fas in the liver. In the cecum, acetate decreased while butyrate increased, with butyrate-producing bacteria becoming dominant. The results of this study indicate that, regardless of a normal diet or high-fat diet, low-dose CYP exposure in male C57BL/6J mice did not significantly affect body weight. However, CYP increased blood lipid levels and promoted the expression of lipogenesis-related genes in the epididymal fat and liver, which may increase the risk of obesity and lipid metabolism-related chronic diseases. |
