臺灣雜糧作物萃取物減緩高脂及果糖飲食誘導小鼠非酒精性脂肪肝之功效探討

Effect of Taiwanese crop extracts on alleviating NAFLD in high fat and fructose diet fed mice

林延橙(Yen-Cheng Lin)

指導教授 ： 潘敏雄

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2019年)

https://doi.org/10.6342/NTU201904436

摘要

肥胖為全球性的健康議題，而飲食的西化與肥胖息息相關。除了高油脂、高熱量的食物攝取外，含糖飲料對肥胖等健康議題所造成的影響亦不容小覷。文獻指出長期暴露於果糖攝取過量的情況下，易產生代謝性相關疾病，例如: 代謝症候群、心血管疾病、非酒精性脂肪肝等。非酒精性脂肪肝 (non-alcoholic fatty liver disease, NAFLD) 為肝臟代謝性疾病，依其嚴重程度可分為脂肪浸潤、脂肪性肝炎、肝硬化等不同階段。肥胖促使脂質在肝臟過度堆積，進而演變為脂肪肝。另有研究指出，肥胖會使身體處於慢性發炎狀態，進而使非酒精性脂肪肝的病程更加惡化。經由 3T3-L1、RAW264.7 及 HepG2 之細胞模式平臺篩選，結果顯示黑豆、黃豆及紅豆之乙醇萃取物，在抑制脂肪細胞中的油滴累積、抗發炎及減緩脂肪肝形成方面，具有較顯著之效果，故將黑豆、黃豆、紅豆乙醇萃取物 (crops extract, CrE) 混和進行後續之動物實驗。動物模式以 50% 高脂及 20% 果糖飲食 (Western diet, WD) 誘導 C57BL/6J 小鼠肥胖，並給予 5% 的 CrE，評估 CrE 是否具有減緩肥胖及非酒精性脂肪肝形成之功效。實驗結果顯示，5% CrE 可以減緩高脂及果糖飲食誘導之小鼠體重上升、體脂肪生成、血中總膽固醇升高及高尿素血症等情形，並在切片及染色結果證實 5% CrE 具有抑制脂肪細胞肥大和肝臟脂質蓄積的能力。另一方面，5% CrE 可以抑制發炎相關因子，TNF-α、IL-6和 MCP-1 的含量，並具有改善瘦素阻抗的能力。在肝臟脂質代謝中，5% CrE 可透過活化 AMPK 路徑，抑制 SREBP-1c 及 FAS 等與脂質合成之相關蛋白表現量，同時增加下游 CPT1 表現量，促使脂肪酸氧化，並藉由 ACC 的磷酸化，減緩肝臟脂質新生。同時進一步發現 5% CrE 可以透過增強 PI3K/Akt 路徑，改善高血糖、胰島素阻抗及葡萄糖耐受不良的情形。根據文獻，可以推測其功效可能來自 5% CrE 中之類黃酮及花青素等植化素所貢獻。綜合上述，細胞與動物實驗結果具有一致性，證實此細胞平臺可以有效篩選具保健食品開發潛力之臺灣雜糧作物。動物實驗結果顯示黑豆、黃豆、紅豆之乙醇萃取物混合樣品具有減緩肥胖及非酒精性脂肪肝形成、降低血糖及抗發炎之功效。

關鍵字

肥胖 ； 非酒精性脂肪肝 ； 果糖 ； 雜糧作物 ； 植化素 ； 血糖

並列摘要

Obesity is a global health issue, and the western diet is closely related to obesity. Besides high-fat diet, the effect of high-calorie food and sugary drinks intake should not be underestimated. Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease of the liver. Depending on its severity, it can be divided into steatosis, hepatitis, and cirrhosis. Obesity causes lipid accumulation in liver and develop into fatty liver. Previous studies pointed out that obesity can cause chronic inflammatory state in body, which in turn worsens the progression of nonalcoholic fatty liver disease. Screening by the cell model platform of 3T3-L1 cells, RAW264.7 cells and HepG2 cells, it showed that the ethanol extract of black soybeans, soybeans and adzuki beans had significant effects in adipogenesis prevention, anti-inflammatory and inhibiting the formation of fatty liver. The mixture of black soybean, soybean, and adzuki bean crops extract (CrE) was chosen as supplementary component in animal experiments. Animal model induced obesity in C57BL/6J mice with a 50% high-fat and 20% fructose diet (WD) and the experimental group was supplemented with 5% CrE to evaluate the ameliorative effect of CrE on obesity and non-alcoholic fatty liver formation. The results showed that 5% CrE could alleviate the weight gain, body fat ratio, elevated total cholesterol and urid acid production in mice induced by high-fat and fructose diets. The results of H&E staining confirmed that 5% CrE exerted ability to inhibit adipocyte enlargement and liver lipid accumulation. On the other hand, 5% CrE was capable to inhibit inflammation and improve leptin resistance. For the underlying mechanism of liver lipid metabolsim, 5% CrE could activate the AMPK pathway, inhibit the expression of SREBP-1c, FAS proteins expression related to lipid synthesis, and increase the expression of downstream CPT1, promoting fatty acid oxidation, and slow liver lipid regeneration by ACC phosphorylation. At the same time, it was further found that 5% CrE could improve the symptoms of hyperglycemia, insulin resistance and glucose intolerance by enhancing the PI3K/Akt pathway. In summary, the consistency in the results of in vitro and in vivo studies indicated that cell platform could be effective for functionality of potential Taiwan crops screening, and the mixture of ethanol extracts of black soybean, soybean and adzuki bean exhibited positive impact on improving obesity and non-alcoholic fatty liver formation, lowering blood sugar and preventing inflammation.

並列關鍵字

Obesity ； Non-alcoholic fatty liver disease (NAFLD) ； Fructose ； Crop ； Phytochemical ； Blood sugar

參考文獻

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