仙草酒水萃取物改善高脂飲食所誘導肥胖大鼠透過調節腸道菌群與分子作用機轉

Anti-obesity effect of Hsian-tsao (Mesona procumbens Hensl.) water and ethanolic extracts in obese rats induced by high-fat diet via the regulation of gut microbiota and molecular mechanism

李怡宣(Yi-Hsuan Lee)

指導教授 ： 林以勤

共同指導教授 ： 徐慶琳(Chin-Lin Hsu)

中山醫學大學/健康管理學院/營養學系/碩士(2022年)

https://doi.org/10.6834/csmu202200199

摘要

肥胖為現今全球重要的公共衛生議題之一，其可能會導致第二型糖尿病、脂肪肝、心血管疾病或是癌症等問題，而有效的預防是防止肥胖盛行率增加的方法。仙草富含多種酚酸，已知酚酸具有抗氧化、抗發炎及抗肥胖等作用，過去文獻指出，仙草能改善肥胖小鼠之高血脂症，但對於調節體脂肪研究較少。因此本研究將探討仙草萃取物是否具有改善體脂肪之作用，以及其對腸道菌群與分子機轉之影響。將四十八隻五週齡雄性Wistar大鼠預養一週後，隨機分成兩組，分為：正常飲食組 (n=8) 及高脂飲食組 (n=40)，誘導高脂飲食組與正常飲食組體重相差10%，並排除未達標準之老鼠，高脂飲食組再隨機分成五組 (n=6/組)，即開始介入仙草萃取物 (200 mg/kg rat)。試驗期間組別包括：(1) 正常飲食組 (normal diet, ND)、(2) 高脂飲食組 (high fat diet, HFD)、(3) 高脂飲食給予仙草桃園1號40%酒水萃取物 (40% ethanolic extracts of Hsian-tsao Taoyuan 1, 40EEHT1) (HFD+40EEHT1)、(4) 高脂飲食給予仙草桃園2號40%酒水萃取物 (HFD+40EEHT2)、(5) 高脂飲食給予仙草桃園1號水萃取物 (water extracts of Hsian-tsao Taoyuan 1, WEHT1) (HFD+WEHT1)、(6) 高脂飲食給予仙草桃園2號水萃取物 (HFD+WEHT2)。實驗為期八週，期間每週記錄攝食量、體重及飲水量。結果發現，高脂飲食給予仙草40%酒水萃取物之組別，可顯著降低最終體重、腹膜外脂肪重量、肝總脂肪含量。由腸道菌群結果顯示，高脂飲食給予仙草萃取物皆可顯著降低Firmicutes之相對豐富度，給予WEHT1之組別可顯著增加Bacteroidetes之相對豐富度。此外，高脂飲食給予仙草萃取物，皆可增加丁酸之含量，給予40EEHT1之組別可顯著增加乙酸及總短鏈脂肪酸之含量。在肝臟及腎周脂肪組織基因結果顯示，給予仙草萃取物之組別，皆可增加脂肪氧化及分解 (ATGL、HSL、CPT-1及ACO) 與減少脂肪合成 (ACC及FAS) 之相關基因表現。綜合上述結果顯示，補充仙草萃取物可改善高脂飲食引起的腸道菌群失衡及增加短鏈脂肪酸含量，也可以調控脂肪代謝相關基因之表現，使脂肪合成減少，並增加分解，達到改善高脂飲食誘導肥胖大鼠體脂肪之作用。

關鍵字

仙草 ； 酚酸 ； 抗肥胖 ； 高脂飲食 ； 腸道菌群

並列摘要

Obesity is an important public health issue around the world. It may lead to problems such as type 2 diabetes, fatty liver, cardiovascular disease, or cancer. An effective prevention is a way to prevent the increased prevalence of obesity. Hsian-tsao is rich in a variety of phenolic acids, which are known to have antioxidant, anti-inflammatory and anti-obesity effects. Previous publications have revealed that Hsian-tsao can improve hyperlipidemia in obese mice, but there are few studies on the regulation of body fat. Therefore, the objective of the study would investigate whether the extracts of Hsian-tsao have the effect on reducing body fat and its effect on the gut microbiota and molecular mechanism. After one week of accommodation, forty-eight male Wistar rats were divided into normal and obese groups, and the obese rats were prefed a high-fat diet. After induction with a 10% difference between the body weight of the normal group, the intervention of the Hsian-tsao extract (200 mg/kg rat) was started. During the experiment, the obese group was randomized into five groups (n=6/group). Groups include: normal diet (ND), hight-fat diet (HFD), hight-fat diet+40% ethanolic extracts of Hsian-tsao Taoyuan 1 (HFD+40EEHT1), HFD+40EEHT2, hight-fat diet+water extracts of Hsian-tsao Taoyuan 1 (HFD+WEHT1), and HFD+WEHT2. The experiment lasted for eight weeks. The results showed that the final body weight, the weight of retroperitoneal adipose tissue, and the total liver lipid in HFD+40EEHT were significantly decreased as compared to HFD. In the gut microbiota, HFD+Hsian-tsao extracts significantly decreased the relative abundance of Firmicutes. HFD+WEHT1 significantly increased the relative abundance of Bacteroidetes. Furthermore, the HFD+Hsian-tsao extracts groups significantly increased short chain fatty acids. In the gene expressions in liver and adipose tissue, the HFD+Hsian-tsao extracts groups increased ATGL, HSL, CPT-1, and ACO, but downregulated ACC and FAS. The results demonstrated that the Hsian-tsao extracts can improve the imbalance of gut microbiota and increase the content of SCFAs caused by high-fat diet induction, and it can also regulate gene expression, reduce fat synthesis, and increase lipolysis, so as to ameliorate the body fat accumulation of obese rats induced by a high fat diet.

並列關鍵字

Hsian-tsao ； phenolic acid ； anti-obesity ； high-fat diet ； gut microbiota

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