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Effect of Lactobacillus brevis 119-2 isolated from turnip M-bM-^@M-^\Tsuda kabuM-bM-^@M-^] on hepatic cholesterol level in cholesterol-administrated rat

ABSTRACT: In previous in vitro study, we reported potential mechanism of cholesterol-lowering effect of Lactobacillus brevis119-2 (119-2) isolated from turnip M-bM-^@M-^\Tsuda kabuM-bM-^@M-^] is due to incorporation of cholesterol into 119-2 cell. In this study, we analyzed serum cholesterol and hepatic gene expression of Sprague-Dawley (SD) rat fed diet containing cholesterol with or without 119-2 for 2 weeks, to evaluate the cholesterol-lowering effect of 119-2 in vivo. Serum cholesterol of SD rat fed diet with 119-2 significantly decreased compared to SD rat fed diet without 119-2, and both viable and dead 119-2 indicated the effect. The result of hepatic gene analysis using DNA microarray suggested that potential mechanism of the cholesterol-lowering effect of 119-2 in vivo is inhibiting the activity of 3-hydroxy-3-methylglutaryl-CoA reductase by Insig (insulin induced gene) that is endoplasmic reticulum membrane protein, and catabolizing cholesterol to bile acid by Cyp7a1 (cytochrome P450 a1) that is the rate-limiting enzyme in the synthesis of bile acid from cholesterol. In addition, we concluded feeding 119-2 decreased serum low density lipoprotein (LDL) cholesterol by overexpression of Ldlr (LDL receptor gene). On the other hand, feeding Lactobacillus acidophilus ATCC43121 (ATCC) increased high density lipoprotein (HDL) cholesterol by over expression of Abca1 (ATP binding cassette sub-family A member 1 gene) and Angplt3 (Angiopoietin-like 3). These results suggested that 119-2 decrease the risk of atherosclerosis by serum cholesterol-lowering effect and improving effect of fatty liver and the LH (LDL cholesterol / HDL cholesterol) ratio. Lactobacillus brevis119-2 (119-2) was isolated from turnip M-bM-^@M-^\Tsuda kabuM-bM-^@M-^] harvested in Matsue city, Shimane Prefecture, Japan, and was stored at Shimane Institute for industrial Technology. Male Jcl: SD rat (4 weeks of age) were obtained from CLEA Japan, Inc. (Tokyo, Japan). Rats were maintained under controlled environmental conditions (temperature 23 M-BM-1 3 M-KM-^ZC, relative humidity 55% M-BM-1 25%, 12/12hr light - dark cycle) and given food and water ad libitum. All rats were acclimated 1 week prior to the experiment. Two groups of 11 rats each were treated respective group diets for 2weeks. Control group was fed high-cholesterol diet containing 10 g cholesterol/kg, 5 g cholic acid/kg, 985 g mouse & rat & rabbit diet (CRF-1) /kg obtained from Oriental yeast Co., Ltd (Tokyo, Japan). The other group was fed same highcholesterol diet with 10 g freeze-dried viable 119-2 /kg. This study and all procedures were approved by regulations and code of ethics in experimental animals Chitose Japan Food Research Laboratories.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Yuji Nakai

PROVIDER: E-GEOD-41734 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Effect of Lactobacillus brevis 119-2 isolated from Tsuda kabu red turnips on cholesterol levels in cholesterol-administered rats.

Watanabe Shinobu S Katsube Takuya T Hattori Hideki H Sato Hiromasa H Ishijima Tomoko T Nakai Yuji Y Abe Keiko K Sonomoto Kenji K

Journal of bioscience and bioengineering 20130214 1

In a previous in vitro study, we reported that the potential mechanism of the cholesterol-lowering effect of Lactobacillus brevis 119-2 isolated from turnip Tsuda kabu was the incorporation of cholesterol to cell membrane. In this study, we analyzed serum cholesterol and hepatic gene expression of Sprague-Dawley (SD) rats kept on a cholesterol diet with or without L. brevis 119-2 for 2 weeks, to evaluate the cholesterol-lowering effect in vivo. Serum cholesterol levels were significantly reduced ...[more]

PMID: 23415664

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Project description:Background: It is recognized that atherosclerosis can regresses at least in animal models. However, little is known about the mechanisms. We induced regression of advanced atherosclerosis in apolipoprotein E deficient (APOE/) mice and studied underlying mechanisms. Unexpectedly, our study led to the role of interleukin-7 (IL-7) in atherogenesis. Methods and Results: We treated APOE/ mice fed a high cholesterol diet for 30 weeks to induce advanced lesions with a helper-dependent adenoviral vector expressing human apoE3 (HDAd-gE3), and analyzed the regression of atherosclerosis after 41 weeks. Using microarray analysis, we identified IL-7 as one of most significantly affected genes by lowering cholesterol. To answer why IL-7 is downregulated by reduced cholesterol, we studied effects of IL-7 on endothelial cells (ECs). Our major findings were (1) long-term lowering cholesterol induced regression of advanced atherosclerosis. (2) Microarray analysis identified multiple signaling pathways affected by lowering cholesterol. (3) Correction for multiple testing revealed that IL-7 expression was downregulated, whereas gamma-sarcoglycan and Î±-actin were upregulated. (4) Oxidized LDL upregulated IL-7 expression in macrophages but not in aorta ECs or smooth muscle cells. (5) IL-7 increased the expression of cell adhesion molecules and chemokine in ECs and promoted monocyte adhesion to ECs. (6) Systemic elevation of IL-7 induced inflammatory response and recruited monocyte/macrophage to the lesions without increasing plasma cholesterol. Conclusion: Our finding suggest that IL-7 inflames endothelium and triggers the adhesion/recruitment of monocyte/macrophages to the atherosclerotic lesions and thus plays a direct role in development of atherosclerosis. Key Words: arteriosclerosis, gene therapy, hypercholesterolemia, interleukins, cell adhesion molecules Female APOE-/- mice (8 weeks of age) on a C57BL/6 background were purchased from Jackson Laboratory and were fed a diet containing 0.2% (w/w) cholesterol and 10% (v/w) coconut oil to induce atherosclerosis for 30 weeks. Mice were then divided into 3 groups, (n=15/group), treated with a tail vein injection of helper-dependent adenovirus expressing human apolipoprotein E3 (HDAd-gE3, 5 x 1012 viral particles/kg, n=11, vector), empty vector (HDAd-0, 5 x 1012 VP/kg, n=11, vector control) or phosphate buffered saline (PBS, vehicle) and sacrificed 10 days after. Three aortas extending sinus to arch were pooled for RNA extraction with an RNeasy kit (Qiagen). Sample ID 12031: E4: vector control (HDAd-0) 12043: E5: vector control 12046: V2: vector 12047: V3: vector 12048: V4: vector 12051: B1: vehicle (PBS) 12053: B3: vehicle 12054: B4: vehicle 12039: E3: vector control

Dataset Information

Effect of Lactobacillus brevis 119-2 isolated from turnip M-bM-^@M-^\Tsuda kabuM-bM-^@M-^] on hepatic cholesterol level in cholesterol-administrated rat

Publications

Effect of Lactobacillus brevis 119-2 isolated from Tsuda kabu red turnips on cholesterol levels in cholesterol-administered rats.

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