Studies on the mechanisms of Lactobacillus on ameliorating the complications in chronic metabolic diseases

Autor: Feng-Chin Hsieh, 謝豐欽
Rok vydání: 2017
Druh dokumentu: 學位論文 ; thesis
Popis: 105
Type 2 diabetes mellitus (DM), characterized by peripheral insulin resistance, is the most common form of diabetes comprising 80 % of all diabetic population. Probiotics are living microorganisms when taken in adequate amount may provide benefits to the host including modulation of DM development. Several lines of evidences have demonstrated the efficacy of Lactobacillus on reducing blood glucose and preventing the development of diabetic complications in type 1 diabetic animal models. Our previous studies also showed that live Lactobacillus reuteri GMNL-263 (Lr263), a common probiotic strain which is commercially available as a healthy food in Taiwan, protected streptozotocin-induced rats (animal model of type 1 diabetes) from development of hyperglycemia-induced renal fibrosis. However, the effects of Lactobacillus on metabolic syndrome and its related complications have not been clarified. Therefore, our study aimed to elucidate this critical issue by performing two animal experiments and explored the possible mechanisms involved. In the first animal experiment, male Sprague–Dawley rats were fed a high-fructose diet with or without Lr263 administration for 14 weeks. The composition of fecal microbiota, oral glucose tolerance, glycated haemoglobin, insulin, leptin, C-peptide, and incretins were measured. The markers of liver injury, serum and hepatic lipids profile, activity of hepatic antioxidant enzyme, and proinflammatory cytokines in adipose tissue were investigated. Additionally, the expression of hepatic lipogenic genes and insulin signaling related genes in adipose tissue were also studied. Liver sections were examined for hepatic steatosis using hematoxylin-eosin staining. The result showed that the levels of serum glucose, insulin, leptin, C-peptide, glycated hemoglobin, GLP-1, liver injury markers, lipid profile in serum and liver were significantly increased in high-fructose-fed rats. However, after Lr263 administration, the elevation of these parameters was significantly suppressed. Feeding of Lr263 reversed the decreased number of Bifidobacterium species and Lactobacillus species and increased number of clostridium species induced by high fructose treatment. The decreased activities of hepatic antioxidant enzymes in HFD rats were dramatically reversed by Lr263 treatment. Concentrations of IL-6 and TNF-α in adipose tissue which were elevated in high fructose treatment were markedly decreased after Lr263 feeding. Decreased levels of PPAR-γ and GLUT4 mRNA after high fructose treatment were significantly enhanced by Lr263 administration. Lr263 consumption normalized the increased lipogenic gene (Srebp-1c, FAS, and Elvol6) expressions stimulated by high fructose. Administration of Lr263 significantly ameliorated hepatic steatosis observed in high fructose treated rats. The objective of second study was to investigate and compare the effects of heat-killed (HK) and live Lactobacillus reuteri GMNL-263 (Lr263) on insulin resistance and its related complications in high-fat diet (HFD)-induced rats. Male Sprague-Dawley rats were fed with a HFD with either HK or live Lr263 for 12 weeks. The increase in weight gain, serum glucose, insulin, and lipid profile in serum and liver observed in HFD group were significantly reduced after HK or live Lr263 administration. Feeding of HK or live Lr263 reversed the decreased number of probiotic bacteria and increased number of pathogenic bacteria induced by high-fat treatment. The decreased intestinal barrier in HFD group was markedly reversed by HK or live Lr263 treatments. The elevations of pro-inflammatory associated genes expressions in both adipose and hepatic tissues by high-fat administration were markedly decreased by HK or live Lr263 treatments. The increased macrophage infiltration noticed in adipose tissue after high-fat treatment was effectively suppressed by HK or live Lr263 consumption. The insulin resistance associated gene expressions in both adipose and hepatic tissues which were downregulated in HFD group were markedly enhanced after HK or live Lr263 feeding. HK or live Lr263 consumption significantly decreased hepatic lipogenic gene expressions stimulated by high-fat treatment. Administration of HK or live Lr263 significantly reduced hepatic oil red O staining and ameliorated hepatic steatosis observed in high-fat treated rats. Our data suggested that similar to live Lr263, HK Lr263 exerted significant effectiveness on attenuating obesity-induced metabolic abnormalities by reducing insulin resistance and hepatic steatosis formation. Our study provided evidences clarifying the effectiveness of Lr263 on reducing insulin resistance as well as hepatic steatosis and suggested that Lr263 may be a promising healthy agent in improving metabolic syndrome.
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