Lactobacillus paracasei 發酵薑黃粉抗肥胖之功效

Abstract

飲食攝取不當及缺乏活動，使熱量的攝取和消耗失去平衡，造成脂肪肥大及慢性發炎。發炎因子藉由降低組織胰島素受體敏感性而造成胰島素阻抗情形產生，進一步加劇肝臟脂質累積。近年許多研究指出腸道菌相失調也與肥胖相關。薑黃來自薑黃的根莖，動物實驗指出薑黃具有降低發炎及血脂功效。Lactobacillus paracasei 副乾酪乳桿菌為一種常應用於發酵產品的乳酸菌。近年研究表示L. paracasei 發酵綠茶減緩大鼠體重增加功效優於未發酵綠茶。然而目前對於L. paracasei 發酵薑黃在抗肥胖效果尚未明瞭，因此本研究以 50% 高脂飲食誘導小鼠肥胖模式，探討 5% L. paracasei 發酵薑黃粉 (F) 減緩肥胖之效果。 成分分析顯示，薑黃粉發酵後其類薑黃素含量減少。動物實驗結果顯示，與 HFD (High-Fat-Diet)相比，未發酵薑黃粉 (U) 和 發酵薑黃粉 (F) 皆顯著調降肝臟三酸甘油酯累積、血清三酸甘油酯和空腹血糖濃度、性腺脂肪肥大，並恢復肝臟胰島素受體路徑蛋白表現量。此外，F 顯著減少體重增加、肝臟重量、性腺脂肪重量、血清總膽固醇濃度。進一步探討，F 降低性腺脂肪的脂肪新生、脂質合成及發炎相關蛋白表現量。F 也透過增加性腺脂肪胰島素受體路徑蛋白，達到改善胰島素阻抗作用。在肝臟脂質代謝上，F 增加脂肪酸 β-氧化並減少脂質合成相關蛋白表現量。與 U 相比，F 於體重、肝臟及性腺脂肪重量、性腺脂肪肥大、脂肪新生、脂質合成作用、脂肪發炎情形、葡萄糖受體路徑、肝臟脂質代謝中SIRT 1、PPARα 和 PGC-1α蛋白表現量的改善作用較為顯著。腸道菌相分析結果顯示，U 和 F 介入皆能調節腸道菌相組成。與 U 相比，F 則顯著增加有益菌 Eggerthella sinensis JCM 14551、短鏈脂肪酸產生菌 Anaerostipes hadrus、[Bacteroides] pectinophilus 並顯著降低有害菌 Roseburia faecis 比例，進而增加小鼠糞便中丙酸鹽濃度。 綜合上述結果，F 可能藉由減少小鼠性腺脂肪的脂肪新生和脂質合成、發炎、改善性腺脂肪與肝臟胰島素受體敏感性，減少肝臟脂質累積，以及調控腸道菌相以達到改善高脂飲食誘導肥胖作用。F 於部分臟器及分子機制的作用效果大於 U，而薑黃經Lactobacillus paracasei發酵後產生脂代謝物可能扮演關鍵角色。

Improper eating habits and lack of physical activity can cause an imbalance of calorie consumption and expenditure, which results in adipocyte hypertrophy and chronic inflammation. Increasing inflammatory cytokines may consequently lead to insulin resistance by reducing tissue insulin receptor sensitivity and subsequently exacerbating lipid accumulation in the liver. Besides, recent studies have pointed out that gut microbiota dysbiosis is associated with the incidence of obesity. Turmeric is derived from the rhizome of Curcuma longa. It has beneficial properties to relieve inflammation and hyperlipidemia in previous animal studies. Lactobacillus paracasei is a lactic acid bacteria species that has been widely used in fermented products. A previous study showed that the effect of L. paracasei fermented green tea in reducing weight gain in rats could be better than unfermented green tea. Yet, the anti-obesity effects of L. paracasei fermented turmeric haven’t been investigated. Therefore, an animal study is designed to clarify the ameliorative effect of 5% L. paracasei fermented turmeric on 50% High-Fat-Diet (HFD)-induced obesity in mice. Our results showed that curcuminoid content of turmeric was decreased after fermentation. In vivo study showed that both unfermented turmeric (U) and L. paracasei fermented turmeric (F) significantly reduced liver triglyceride accumulation, serum triglyceride and fasting blood glucose levels, perigonadal adipocyte hypertrophy, and restored the expression of hepatic insulin receptor pathway protein expressions. Furthermore, F significantly suppressed the body weight gain, liver weight, perigonadal adipose tissue weight, and serum total cholesterol levels. In addition, F downregulated the expressions of adipogenesis, lipogenesis and inflammatory–related protein in perigonadal adipose tissue. F also ameliorated insulin resistance via activating insulin receptor pathway protein expressions in perigonadal adipose tissues. For liver lipid metabolism, F increased fatty acid β-oxidation and decreased lipogenesis–related protein expressions. In particular, F exerted greater effects on improved body weight gain, liver and perigonadal tissue weight, perigonadal adipocyte hypertrophy, adipogenesis, lipogenesis, inflammation, insulin receptor pathway, liver fatty acid β-oxidation protein SIRT 1, PPARα, and PGC-1α than U. Gut microbiota analysis showed that U and F modulated microbiota composition. Compared with U, F significantly increased the beneficial bacteria Eggerthella sinensis JCM 14551, short-chain fatty acid-producing bacteria Anaerostipes hadrus, [Bacteroides] pectinophilus and significantly reduced the proportion of harmful bacteria Roseburia faecis, thereby increasing propionate concentrations in mouse feces. In summary, our results suggest that fermented turmeric (F) may be beneficial for obesity prevention by reducing adipogenesis, lipogenesis and inflammatory responses in perigonadal adipose tissues, improving the insulin sensitivity of perigonadal adipose tissue and liver, reducing liver lipid accumulation, and regulating the gut microbiota. Compared with U, F had more significant anti-obesity effects on some organs and molecular mechanisms, and the metabolites produced by turmeric fermentation by Lactobacillus paracasei may play a key role.