- 學位論文
乳酸菌補充劑對高脂飲食誘導肥胖大鼠之抗肥胖作用及其分子機制探討
Antiobesity effects of lactic acid bacteria supplements on high-fat diet-induced obese rats and their molecular mechanisms
摘要
肥胖為全球重要之公共衛生議題，其會伴隨許多代謝紊亂症候群，例如:第二型糖尿病、血脂質異常和高血壓。研究指出，益生菌可藉由調整腸道菌群組成，進而改善能量代謝並預防肥胖和相關慢性疾病之發生，故近年來利用益生菌作為抗肥胖作用之研究逐漸受到重視。本實驗分為二部分：(一) 以動物模式評估七種潛力機能性樣品之抗肥胖作用。(二) 將易得孅乳酸菌 (Lactobacillus plantarum GKM3) 給予肥胖大鼠，探討其抗肥胖作用與分子機制。結果顯示，(一) 在七種潛力機能性樣品中，以乳酸菌機能性樣品 (HMZ-337) 最具抑制高脂飲食誘導肥胖大鼠之體重、肝臟、全身總脂肪和內臟脂肪組織之重量，並降低肝臟總脂質、三酸甘油酯和膽固醇含量。在肝臟和脂肪組織切片中，其可顯著抑制高脂飲食誘導之肝臟油滴堆積和脂肪細胞肥大。(二) 給予易得孅益生菌膠囊中劑量 (205.4 mg/kg rat/day) 可顯著抑制高脂飲食誘導之肥胖大鼠之體重、肝臟重量、全身總脂肪和內臟脂肪組織重量，以及降低肝臟總脂質、三酸甘油酯和膽固醇含量，並增加糞便總脂質、三酸甘油酯和膽固醇排出。在肝臟和脂肪組織切片中，給予易得孅益生菌膠囊可顯著減少高脂飲食誘導之肝臟油滴堆積和腎周圍脂肪細胞肥大。在脂肪組織之基因表現上，給予肥胖大鼠易得孅益生菌膠囊中劑量 (205.4 mg/kg rat/day) 以上之組別，可提升脂質合成抑制基因 (SIRT1)、脂肪酸氧化 (AMPK、PGC-1α、PGC-1β、CPT-1和ACO)、脂質分解 (ATGL與HSL) 和脂肪細胞激素 (adiponectin) 之相關基因表現，並降低脂質生合成 (PPAR-γ、SREBP-1c、ACC和FAS)、脂質代謝 (aP2) 和脂肪細胞激素相關基因 (TNF-α) 之基因表現。在肝臟基因表現上，給予易得孅益生菌膠囊中劑量 (205.4 mg/kg rat/day) 以上之組別，亦可提升脂質合成抑制基因 (SIRT1)、脂肪酸氧化 (AMPK、PGC-1α和ACO) 和脂質分解相關基因 (ATGL與HSL) 之基因表現。並抑制脂質生合成相關基因 (PPAR-γ、SREBP-1c、ACC和FAS) 之基因表現。綜合上述實驗結果顯示，易得孅益生菌膠囊【植物乳酸菌凍乾粉 (Lactobacillus plantarum GKM3)】為具有開發不易形成體脂肪功能之潛力樣品。
並列摘要
Obesity has been recognized as a major public health problem, accompanied by numerous metabolic disorders, such as type 2 diabetes, dyslipidemia, and hypertension. Previous study indicated that probiotics can modulate the composition of intestinal flora, thus improve the energy metabolism, reducing obesity, and related chronic disease risk. Therefore, the anti-obesity potential of probiotics is gradually attention in recent years. There are two topics included in this study: (1) Anti-obesity effect of seven potential functional samples on high-fat diet (HFD)-induced obese rats. (2) Anti-obesity and molecular mechanism action of sliim probiotic complex (lactobacillus plantarum GKM3) on high-fat diet (HFD)-induced obese rats. The result indicated that: (1) HMZ-337 had the greatest inhibitions of body weight, liver weight, total body fat, visceral adipose tissue, hepatic total lipid, hepatic triglyceride, and hepatic cholesterol among seven potential functional compounds. In histological analyses of liver and adipose tissue, HMZ-337 could reduce the liver lipid accumulation and adipocyte size as compared to the HFD group. (2) The data indicated that the body weight, total body fat, visceral adipose tissue and liver, and hepatic total lipid, hepatic triglyceride, and hepatic cholesterol in medium dose sliim probiotic complex (205.4 mg/kg rat/day) group significantly decreased as compared with the HFD group. Sliim probiotic complex (205.4 mg/kg rat/day) also increased the excretions of fecal total lipid, fecal triglyceride, and fecal cholesterol as compared with HFD group. In histological analysis of liver and adipose tissue, sliim probiotic complex (205.4 mg/kg rat/day) group significantly decreased the liver lipid accumulation and adipocyte size. In gene expressions of adipose tissue, medium and high dose sliim probiotic complex (205.4 and 513.5 mg/kg rat/day) upregulated the gene expressions of SIRT1, AMPK, PGC-1α, PGC-1β、CPT-1, ACO, ATGL, HSL, and adiponectin, whereas it downregulated the gene expressions of PPAR-γ, SREBP-1c, ACC, FAS, aP2, and TNF-α in the perirenal adipose tissues of HFD rats. In gene expression of liver, sliim probiotic complex (205.4 mg/kg rat/day) significantly increased the gene expressions of SIRT1, AMPK, PGC-1α, ACO, ATGL, and HSL, but downregulated the gene expressions of PPAR-γ、SREBP-1c, ACC, FAS in the liver of HFD rats. The results demonstrated that sliim probiotic complex (lactobacillus plantarum GKM3) can be developed as a potential nutraceutical product for preventing obesity.