探討左旋肉鹼於高脂飲食下肝臟保護功效

Abstract

根據行政院衛福部統計資料顯示，國人脂肪肝盛行率高達26-34%，因此如何減緩脂肪肝成了近年來重要的研究課題。前人研究結果指出，動脈粥狀硬化小鼠補充左旋肉鹼（L-carnitine, CNT）可以有效減少心臟及肝臟中的脂質過氧化物；且於乙醯氨酚(acetaminophen)誘導之急性肝損傷小鼠中，亦能展現其抗氧化能力及對肝臟的保護功效。本研究目標為探討CNT補充於高脂飲食C57BL/6小鼠模式下調節脂質平衡及抗氧化的功效。30隻雄性C57BL/6小鼠隨機分至以下組別：（1）Control組：一般飼糧+蒸餾水；（2）HFD組：高脂飼糧+蒸餾水；（3）CNTL組：高脂飼糧+低劑量CNT (500 mg CNT/kg BW)；（4） CNTH組：高脂飼糧+高劑量CNT (1500mg CNT/kg BW)。動物試驗結果顯示：CNT補充能改善（p<0.05）血脂組成（膽固醇、三酸甘油酯、高密度脂蛋白膽固醇及低密度脂蛋白膽固醇）及減少肝臟脂質堆積。而上述脂質調節效果可能來自於調降（p<0.05）脂質生合成基因表現（Acc, Me, Srebp-2, and Hmgr）及提升（p<0.05）脂肪的β氧化（Pparα, Rxrα, Cpt-1, and Ucp-2）與血清中膽固醇清除（Ldlr）與肝臟中膽固醇代謝（Cyp7a1）基因表現。此外，CNT亦可提高（p<0.05）脂肪β氧化（CPT-1）及能量耗損（UCP-2）之蛋白質表現。補充CNT亦能提高（p<0.05）血中總抗氧化力及提高（p<0.05）肝臟中麩胱甘肽含量及麩胱甘肽過氧化酶活性。此外亦能降低（p<0.05）肝臟中細胞激素（TNF-α）含量藉此達到抗發炎效果。綜觀上述研究結果，於高脂飲食下補充CNT具有抗氧化、調節脂質恆定及抗發炎的效果，對於調降血脂及減緩高脂飲食下導致脂肪肝具有顯著的保健功效。

Liver is an organ where lipid metabolism occurs, so under this condition it’s likely to cause the burden of the liver. About 26-34% people suffer non-alcoholic fatty liver disease (NAFLD) in Taiwan, so how to reduce the prevalence of NAFLD is the most important topic nowadays. Literatures showed that L-carnitine (CNT) could reduce lipid peroxidants in atherosclerotic rats and provide a hepatoprotective effect against acute acetaminophen toxicity in mice. The objectives of this study were to clarify the lipid ameliorative effect and the anti-oxidative capacity of CNT on high-fat-diet fed mice. Thirty male C57BL/6 mice were randomly divided to four groups: 1) control group (CON group): normal diet + ddH2O, 2) high-fat diet group (HFD group: high-fat diet + ddH2O, 3) low-dosage-CNT group (CNTL group): high-fat diet + 500 mg CNT/kg BW, and 4) high-dosage-CNT group (CNTH group): high-fat diet + 1500 mg CNT/kg BW. After a 25-week experimental period, CNT supplement reduced (p<0.05) serum triglyceride (TG), cholesterol (TC) and lipoprotein ratio (LDLC/HDLC), as well as (p<0.05) liver TG contents. Those improvements might be due to a down-regulation (p<0.05) of lipogenesis (Acc, Me, Srebp-2, and Hmgr), and up-regulations of energy expenditure (Pparα, Rxrα, Cpt-1, and Ucp-2) and cholesterol clearance (Ldlr) and catabolism (Cyp7a1). In addition, CNT supplementation also increased (p<0.05) the protein expressions of CPT-1 and UCP-2 expressions, which related to fatty acid β-oxidation and energy expenditure, respectively. Serum trolox equivalent antioxidants capacity (TEAC) level, and liver glutathione (GSH) content and the activity of glutathione peroxidase (GPx) of high-fat-diet fed mice were also increased (p<0.05) by CNT supplementation. Besides, TNF-α contents in livers of high-fat-diet fed mice were also decreased (p<0.05) by CNT supplementation.