記述言語：英語   掲載種別：研究論文（学術雑誌）  

The SHRSP5/Dmcr is a useful animal model for the development of nonalcoholic steatohepatitis (NASH) pathology when fed a high-fat, high-cholesterol diet, and further drug interventions can lead to concomitant cardiovascular disease. While SHRSP5/Dmcr rats have been used for basic research related to NASH, details of their bile acid metabolism in this condition are unknown. In this study, we aimed to clarify the changes in the serum bile acid (BA) fractions associated with NASH and found that glycine-conjugated and unconjugated bile acid increased with worsening NASH and cardiovascular disease while taurine-conjugated BA relatively decreased.

DOI： 10.18926/AMO/64358

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progressive subtype of non-alcoholic fatty liver disease (NAFLD) that is closely related to cardiovascular disease (CVD). Nitric oxide (NO) plays a critical role in the control of various biological processes. Dysfunction of the NO signaling pathway is associated with various diseases such as atherosclerosis, vascular inflammatory disease, and diabetes. Recently, it has been reported that NO is related to lipid and cholesterol metabolism. Chronic NO synthase (NOS) inhibition accelerates NAFLD by increasing hepatic lipid deposition. However, the detailed relationship between NO and abnormal lipid and cholesterol metabolism in NAFLD/NASH has not been completely explained. We aimed to determine the effects of NOS inhibition by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME), a NOS inhibitor, on NASH and CVD via lipid and cholesterol metabolism. METHODS: Stroke-prone spontaneously hypertensive rats were fed a high-fat and high-cholesterol diet for 8 weeks and administered L-NAME for the last 2 weeks. Following blood and tissue sampling, biochemical analysis, histopathological staining, quantitative RT-PCR analysis, and western blotting were performed. RESULTS: L-NAME markedly increased hepatic triglyceride (TG) and cholesterol levels by promoting TG synthesis and cholesterol absorption from the diet. L-NAME increased the mRNA levels of inflammatory markers and fibrotic areas in the liver. Cholesterol secretion from the liver was promoted in rats administered L-NAME, which increased serum cholesterol. L-NAME significantly increased the level of oxidative stress marker and lipid deposition in the arteries. CONCLUSIONS: NOS inhibition simultaneously aggravates NASH and atherosclerosis via hepatic lipid and cholesterol metabolism.

DOI： 10.1007/s43440-022-00380-1

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mechanomyogram (MMG) is a signal measured by various vibration sensors for slight vibrations induced by muscle contraction, and it reflects the muscle force during electrically induced-contraction or until 60%-70% maximum voluntary contraction, so the MMG is considered an alternative and novel measurement tool for muscle strength. We simultaneously measured the MMG and muscle force in the gastrocnemius (GC), vastus intermedius (VI), and soleus (SOL) muscles of rats. The muscle force was measured by attaching a hook to the tendon using a load cell, and the MMG was measured using a charged-coupled device-type displacement sensor at the middle of the target muscle. The MMG-twitch waveform was very similar to that of the muscle force; however, the half relaxation time and relaxation time (10%), which are relaxation parameters, were prolonged compared to those of the muscle force. The MMG amplitude correlated with the muscle force. Since stimulation frequencies that are necessary to evoke tetanic progression have a significant correlation with the twitch parameter, there is a close relationship between twitch and tetanus in the MMG signal. Therefore, we suggest that the MMG, which is electrically induced and detected by a laser displacement sensor, may be an alternative tool for measuring muscle strength.

DOI： 10.1016/j.jelekin.2021.102627

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is linked to an increased risk of cardiovascular disease, regardless of the risk factors in metabolic syndrome. However, the intermediary factors between NASH and cardiovascular disease are still unknown. A previous study revealed that serum and hepatic bile acid (BA) levels are increased in some NASH patients. We aimed to examine whether NASH and cardiovascular disease were aggravated by BA using an animal model. METHOD AND RESULTS: From 10 to 18 weeks of age, SHRSP5/Dmcr rats divided into 3 groups were fed 3 types of high-fat and high-cholesterol (HFC) diets which were changed in the cholic acid (CA) concentration (0%, 2%, or 4%). The nitro oxide synthase inhibition (L-NAME) was administered intraperitoneally from 16 to 18 weeks of age. The 4% CA groups showed the worst LV dysfunction and myocardial fibrosis, and demonstrated severe hepatic fibrosis and lipid depositions. In addition, a large amount of lipid accumulation was observed in the aortas of the 4% CA group, and NFκB and VCAM-1 gene expression levels were increased. These findings were not seen in the 0% CA group. CONCLUSION: In the SHRSP5/Dmcr rat model, NASH and cardiovascular disease were aggravated with increasing BAs concentrations in an HFC diet.

DOI： 10.1016/j.yexmp.2020.104437

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The non-alcoholic steatohepatitis (NASH) increases the cardiovascular risk regardless of risk factors in metabolic syndrome. The stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr), fed a high-fat and -cholesterol (HFC) diet and administered Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) presented NASH and cardiovascular disease. However, the intermediary factors between NASH and cardiovascular risk are still unknown. We investigated whether bile acids (BAs) play an intermediary role between NASH and cardiovascular disease in SHRSP5/Dmcr rats. SHRSP5/Dmcr rats divided into 2 groups were fed an SP (non-NASH group, n=7) or HFC diet (NASH group, n=10) for 8 weeks. L-NAME was administered intraperitoneally in the final 2 weeks. In the
NASH group, total BA levels were increased in both serum and liver; they aggravated the endothelial dysfunction in aorta, which is the first step to atherosclerosis, and activated the gene expression levels of cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1) in coronary artery. In particular, the nuclear factor-kappa B (NFkB) was increased in the NASH group in the coronary endothelial cells activated by high BA levels. We demonstrated that liver BAs aggravated steatosis and fibrosis and serum BA accelerated arteriosclerosis and ischemic heart disease via the classical pathway of NFkB in the endothelial cells. BA metabolism disorder may
be an intermediary factor between NASH and cardiovascular risk in SHRSP5/Dmcr rats.

DOI： 10.35248/2155-9600.19.9.1000763

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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開催年月日： 2023年2月15日 - 2023年2月19日

記述言語：英語   会議種別：ポスター発表  

開催地：Taipei  

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開催年月日： 2022年7月23日 - 2022年7月24日

記述言語：日本語   会議種別：ポスター発表  

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開催年月日： 2021年10月23日 - 2021年10月24日

記述言語：日本語   会議種別：ポスター発表  

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開催年月日： 2021年10月23日 - 2021年10月24日

記述言語：日本語   会議種別：ポスター発表  

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開催年月日： 2021年9月10日 - 2021年9月11日

記述言語：英語   会議種別：口頭発表（一般）  

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