以高脂飲食誘導肥胖大鼠模式探討補充胚芽乳酸桿菌GKM3對抑制脂質合成與腸道菌群之影響

肥胖為現代國家嚴重的健康問題之一，其會造成慢性代謝疾病的盛行率上升，其中，預防肥胖並維持理想體重，已知是有效降低慢性疾病罹患風險的策略之一。補充乳桿菌可調節腸道菌群的組成，進而改變宿主的生理代謝機制，亦可作為預防與治療肥胖症之潛力樣品。因此本研究將探討補充胚芽乳酸桿菌 (Lactobacillus plantarum) GKM3對於高脂飲食誘導之肥胖大鼠，是否能達到抗肥胖之作用，以及其對腸道菌相與分子機制之影響。將40隻6週齡雄性Wistar大鼠預養一週後，隨機分成五組：正常飲食組 (Normal diet, ND)、高脂飲食組 (High fat diet, HFD)、低劑量組 (HFD+low dose, HFD+LD, 102.7 mg/kg rat/day)、中劑量組 (HFD+medium dose, HFD+MD, 205.4 mg/kg rat/day) 以及高劑量組 (HFD+high dose, HFD+HD, 513.5 mg/kg rat/day)，每週記錄攝食量、飲水量及體重變化，進行為期八週的實驗。結果顯示，高脂飲食誘導之肥胖大鼠在補充胚芽乳酸桿菌GKM3後，其可顯著降低肥胖大鼠之最終體重、內臟脂肪重量與肝臟脂肪含量，且能增加糞便脂肪之排出。在菌相結果顯示，給予胚芽乳酸桿菌GKM3能增加與短鏈脂肪酸呈正相關之菌群豐度，並提高體內短鏈脂肪酸之含量，更減少了與肥胖呈正相關之菌群豐度。抗肥胖相關分子作用機轉的部分，中劑量與高劑量組別能增加肝臟脂肪分解和減少脂肪合成之相關基因表現，亦能提高棕色脂肪之生熱基因表現。此外，給予胚芽乳酸桿菌GKM3之組別，其降低了肥胖大鼠血中脂多醣濃度與脂肪組織中TNF-α和IL-1β之表現量。綜合上述結果得知，胚芽乳酸桿菌GKM3能藉由逆轉高脂飲食之菌相組成與增加短鏈脂肪酸之含量，進而調控相關基因之表現量，使高脂飲食誘導之肥胖大鼠體內脂肪堆積減少與能量釋出增加；研究亦顯示，因體內益生菌之增加，使脂多醣通透至血中濃度下降，減輕了肥胖所誘導之發炎反應。總結以上研究，補充胚芽乳酸桿菌GKM3確實具有抗肥胖之作用。

關鍵字

胚芽乳酸桿菌GKM3 ；肥胖大鼠；高脂飲食；腸道菌相；發炎

並列摘要

Obesity is one of the serious health problems in modern countries, which leads to an increase in the prevalence of chronic metabolic diseases. Among them, preventing obesity and maintaining an ideal body weight is known to be one of the strategies to effectively reduce the risk of chronic diseases. Lactobacillus can regulate the composition of the gut microbiota, thereby changing the metabolic mechanism of the host, and can also be used as a potential sample for the treatment of obesity. Therefore, this study aimed to investigate the anti-obesity effects of Lactobacillus plantarum GKM3 in high-fat diet-induced obese rats, and its effect on gut microbiota and molecular mechanisms. After one week accommodation, forty, and six-week-old male Wistar rats were divided into five groups (n=8/group): normal diet (ND), high fat diet (HFD), low dose (HFD+LD, 102.7 mg/kg rat/day), medium dose (HFD+MD, 205.4 mg/kg rat/day), and high dose (HFD+HD, 513.5 mg/kg rat/day) group. Food intake, water intake, and body weight changes were recorded weekly for 8 weeks. The results showed that Lactobacillus plantarum GKM3 effectively reduced body weight, visceral fat weight and liver fat content in high-fat diet-induced obese rats, and can increase the excretion of fecal total lipid. The results of the gut microbiota showed that Lactobacillus plantarum GKM3 significantly increased the abundance of bacteria that were positively correlated with SCFAs and the content of SCFAs, and decreased the abundance of bacteria that was positively correlated with obesity. The results of the molecular mechanism showed that the middle- and high-dose groups could increase the expression of genes related to hepatic lipolysis and reduce fat synthesis, and also increased the expression of thermogenic genes in brown fat tissue. Furthermore, Lactobacillus plantarum GKM3 significantly reduced the concentration of LPS in the blood and the expression of TNF-α and IL-1β in the adipose tissue of obese rats. These results demonstrated that Lactobacillus plantarum GKM3 reversed the composition of the gut microbiota by high-fat treatment and increased the content of SCFAs to regulate the expression of genes, which reduces fat accumulation and increases energy release, thus achieving anti-obesity effects. Also due to the increase of probiotics, the concentration of LPS decreases, and the obesity- induced inflammation is alleviated.

並列關鍵字

Lactobacillus plantarum GKM3 ； obese rats ； high-fat diet ； gut microbiota ； inflammation

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