桑葉茶對於高脂飲食誘導小鼠之肥胖及肝臟脂質代謝的影響

Abstract

由於人們生活水平的提高及飲食結構的變化，肥胖的人口逐漸增加。肥胖會增加二型糖尿病、高血脂、心血管疾病、高血壓等疾病患病的風險，對人體的健康造成影響。肝臟是人體代謝碳水化合物、蛋白質和脂質的重要器官，在維持血糖與能量平衡上起著關鍵作用。非酒精性脂肪肝是漸進性的肝臟疾病，是由於非酒精因素導致的肝臟內脂肪積聚而引起，它與代謝綜合征候群 (肥胖、胰島素阻抗與血脂異常等) 密切相關，且嚴重時會導致肝炎、肝纖維化及肝癌的發生，嚴重影響身體健康。本實驗的樣品為桑葉，桑葉中含有豐富的黃酮類成分，具有抗氧化、清除自由基等功能，且已經有文章指出在飲食中混入桑葉粉末或是桑葉萃取物具有預防肥胖及非酒精性脂肪肝之作用，但並沒有以模擬人體攝入茶水的方式進行研究。實驗使用動物模式，選擇 4 週齡 C57BL/6J 小鼠分為四個組別，分別為普通飲食、高脂飲食以及高脂飲食搭配兩種不同濃度 1.5 g/150 mL 及 3.0 g/150 mL 的桑葉茶 (MAL) 進行餵養，探討 MAL 是否具有延緩肥胖及抑制肝臟脂質蓄積之功效。實驗結果證實，MAL 預防了由高脂飲食所導致的血清中天門冬胺酸轉胺酶及三酸甘油酯含量的升高，且在肝臟及脂肪切片中證明了 MAL 可以抑制肝臟脂肪的蓄積以及脂肪細胞的肥大。進一步探討體內分子機制，發現 MAL 可以增加脂肪細胞中 PPARγ、C/EBPα 的蛋白表現量，同時增加脂聯素的表達，從而使脂肪變大的方式由脂肪細胞體積變大向數目增多轉化。此外，MAL 使肝臟中脂聯素的含量上升，進一步促進 AMPK 的磷酸化，從而減少了肝臟脂肪的蓄積。此外，MAL 可以抑制肝臟及脂肪中發炎相關因子 TNF-α，MCP-1，IL-6 及 IL-1β 的生成，達到減少肝臟損傷及發炎反應的功效。綜上所述，桑葉茶可以通過 AMPK 的活化及促進脂肪細胞新生作用對肝臟脂質蓄積及抗發炎方面有一定的改善作用。

Obesity has become a worldwide health issue that rapidly progresses due to changes in lifestyle and diet structure/westernization. It is known obesity as a risk factor, contributes to variety of comorbidities, such as type II diabetes, lipidaemia and cardiovascular diseases. Liver is one of the most important organ for carbohydrate, protein and lipid metabolism, and also a key regulator for blood glucose level via gluconeogenesis pathway. Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that is highly associated to metabolic syndrome, which is also being introduced its occurrence in the setting of insulin resistance and increased adiposity. Excessive fatty acids accumulation in liver is the major characteristic of NAFLD, and the famous “multiple-hit” pathogenic model has suggested the progression of NAFLD into non-alcoholic steatohepatitis (NASH), liver cirrhosis and finally liver cancer. It has been reported that therapy aiming NAFLD can be a potential strategy for improvement of obesity. The sample in this experiment is Morus alba L. (a.k.a white mulberry), which has exhibited antioxidant and free radical scavenging capability because its richness in flavonoid contents. Previous studies have pointed out that mixing mulberry leaf powder or mulberry leaf extract in the diet have the effect of preventing obesity and NAFLD. However, it has not been studied in the way of drinking tea like to person. Animal model was used in the experiment and 4-week-old C57BL/6J mice were selected to be divided into four groups: normal diet, high-fat diet and high-fat diet with two different concentrations of mulberry leaf tea (MAL) of 1.5 g and 3.0 g/150 mL to explore whether MAL has the effects of delaying obesity and inhibiting liver lipid accumulation. The results showed that MAL prevented the increase in serum AST and TG caused by high-fat diet. H&E staining shows that MAL has the ability to inhibit liver fat accumulation and adipocyte enlargement. Further exploring the molecular mechanism in vivo, it was found that MAL can increase the protein expression of PPARγ and C/EBPα in adipocytes, and then increase the expression of adiponectin. It proves that the increase in fat is in the form of hyperplasia rather than hypertrophy. On the other hand, MAL increases the expression of adiponectin in liver and further promotes the phosphorylation of AMPK, which leads to a reduction in the accumulation of liver fat. In addition, MAL can inhibit the content of inflammation factors TNF-α, MCP-1, IL-6 and IL-1β in liver and fat to reduce liver damage and inflammation. In summary, MAL has an improvement effect on liver lipid accumulation and anti-inflammatory by activating AMPK and promoting the regeneration of adipocytes.