細菌素 albusin B 對於肥胖小鼠脂肪與碳水化合物利用之影響

Abstract

肥胖被歸為二十一世紀全球性流行病且與代謝症候群相關，其增加第二型糖尿病與肝炎的風險，因此近年來逐漸備受重視。肥胖之盛行源於現代人生活型態的改變，隨著飲食習慣變遷為高糖高脂之西方飲食，導致人們普遍有肥胖問題。 Albusin B為分子量32 kDa且由Ruminococcus albus 7所分泌之細菌素，藉由Saccharomyces cerevisiae表現系統進行量產。在先前研究發現，餵予健康小鼠albusin B會促進其脂肪代謝並降低小鼠體重，然而albusin B對於肥胖小鼠能量代謝之效應尚未被探討。故本試驗以7週齡C57BL/6公鼠為試驗模式，餵飼小鼠西方飼糧為期20週以誘發其肥胖。肥胖小鼠進而逢機分為3組，食鹽水組（WS），低濃度albusin B組 （0.125 μg albusin B /g體重; WLA），與高濃度albusin B組 （0.625 μg albusin B /g體重; WHA）。小鼠予以灌食食鹽水或albusin B連續4週後犧牲。結果顯示，西方飼糧餵飼20週後之小鼠呈現病態肥胖，其血糖與血脂異常，且具有脂肪肝與脂肪細胞肥大現象。灌食低濃度albusin B顯著降低肥胖小鼠之體重、血液總膽固醇與低密度脂蛋白含量，並且減少肝臟脂肪堆積與脂肪細胞大小。高濃度albusin B無法調節肥胖小鼠之體重與血液生化值，然可降低肥胖小鼠之脂肪細胞大小。灌食albusin B亦降低小腸、肝臟與肌肉對於脂肪酸之吸收。相較於WS組，WLA組小鼠具有較高肝臟與白色脂肪組織之脂質氧化作用，以及較低白色脂肪組織與肌肉之脂質合成作用。另外，albusin B處理降低肥胖小鼠對果糖之吸收且WLA組具有較高肝臟與肌肉之糖解作用。由呼吸商結果證實灌食albusin B可使肥胖小鼠之能量利用轉移至較多的碳水化合物。此外，灌食albusin B可增加抗氧化能力與盲腸內Bifidobacterium之含量。 綜觀上述，口服0.125 μg /g體重albusin B可降低肥胖小鼠之體重，促進其脂質代謝、碳水化合物之利用與抗氧化能力，並改善其盲腸菌相，進而有效改善飲食引起肥胖之小鼠健康。

Obesity is one of the major worldwide epidemics and has became a public health problem of the 21st century because of its association with metabolic syndrome, which increases the risks of developing type 2 diabetes and hepatic steatosis. The expansive prevalence of obesity is caused by the dramatic changes of lifestyle. Western diet, made up of high-fat and high-sugars, is the major dietary concern for obesity prevalence. Albusin B is a 32-kDa bacteriocin from the ruminal bacterium Ruminococcus albus 7 and mass-produced by Saccharomyces cerevisiae expression system. In the previous study, administration of albusin B caused a decrease in body weight (BW) and plasma triglycerides (TG) levels, and improved lipid metabolism of healthy BALB/C mice. However, the effect of albusin B on energy homeostasis of obese mice has not been elucidated. In this study, 7-week-old C57BL/6 male mice were fed with Western diet for 20 weeks to induce obesity. Then the obese mice (W) were randomly assigned to 3 groups: saline (WS), WLA [0.125 μg albusin B /g body weight (BW)], and WHA (0.625 μg albusin B /g BW). Saline / albusin B was orally administrated for extra 4 weeks then sacrificed. Results showed that Western diet induced morbid obesity in mice, including hyperglycemia, dyslipidemia, fatty liver, and hypertrophy of adipocytes. Oral administration of 0.125 μg albusin B/g BW significantly reduced BW, plasma levels of total cholesterol (TC) and low density lipoprotein (LDL), hepatic lipid accumulation, and adipocyte size. High concentration of albusin B did not change BW and lipid profiles in plasma, but reduced adipocyte size. Administration of albusin B decreased fatty acid absorption in the ileum, liver, and muscle. Compared with WS group, WLA group had higher lipid oxidation rate in the liver and white adipose tissue (WAT) and lower lipid synthesis in the WAT and muscle. WHA group had a decrease of lipogenic gene expressions in the WAT as compared to WS group. Moreover, albusin B treatment suppressed hepatic fructose uptake and WLA mice had higher glycolytic gene expressions in the liver and muscle. Administration of albusin B increased the respiratory quotient of obese mice, demonstrated that a higher efficiency of carbohydrate utilization for energy expenditure. Albusin B treatments also promoted systemic antioxidant defense and increased caecal counts of Bifidobacterium. Taken together, oral administration of 0.125 μg albusin B/g BW albusin B resulted in body weight loss and promoted lipid metabolism, carbohydrate utilization, and antioxidant capacity, and elevated caecal population of Bifidobacterium in diet-induced obese mice. These results therefore partially improve the health of obese mice.