MOLECULAR NUTRITION & FOOD RESEARCH
·
2018
·Vol. 62
·期 16
·1800170
·
IF 5.151
Chun-Feng Guo,Ya-Hong Yuan,Tian-Li Yue,Jing-Yan Li
Scope Rats and hamsters are the most commonly used animal models for evaluating the hypocholesterolemic activity of potential probiotic strains, whereas little or no information has been reported on whether the animal models would affect the experimental conclusions regarding the hypocholesterolemic efficacy of the strains. Methods and results Both high-cholesterol-fed rats and hamsters were intragastrically administered viable cells of bile salt hydrolase-active Lactobacillus acidophilus K16 once daily (1 × 10 10 CFU per kg body weight) for 28 d. It was found that the strain did not significantly ( p > 0.05) affect the serum and hepatic cholesterol levels in rats, whereas it significantly decreased ( p < 0.01 or p < 0.001) the serum total and non-HDL-cholesterol as well as hepatic-free, esterified, and total cholesterol levels in hamsters by 29.6%, 38.8%, 15.8%, 36.2%, and 34.0%, respectively. Conclusion These data suggest that the hypocholesterolemic efficacy of L. acidophilus K16 is substantially different between high-cholesterol-fed hamsters and rats and that hamsters are a better model system than rats for evaluating the hypocholesterolemic efficacy of potential probiotic strains due to their similarity to humans in biliary bile acid composition, including types of bile acids and their conjugation form.
研究领域:
营养学
·
微生物学
·
动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Yao Guo,Guangjie Shu,Ziyang Zhang,Xiaoshuang Hu,Huiru Huang,Wenxin Lu,Miaomiao Zhu,Bing Liu,Shenshen Zhang
Cholesterol homeostasis dysregulation is a primary risk factor for atherosclerosis (AS) development. Fisetin, a flavonoid compound, has shown promise in regulating cholesterol homeostasis by enhancing transintestinal cholesterol excretion (TICE). This study aimed to investigate the regulatory effects and underlying mechanisms of fisetin in AS. In this study, ApoE −/− mice fed a high-fat diet (HFD) were employed to investigate the effects of fisetin on the prevention of AS. Various methods, including biochemical analyses, histopathological staining, lipid deposition assessment, untargeted lipidomics analysis and RNA sequencing, were employed to explore the underlying mechanisms. The results showed that treatment with fisetin notably reduced lipid deposition in the aortic root of HFD-treated ApoE −/− mice and attenuated hepatic lipid deposition and histopathological changes. This was accompanied by decreased serum levels of total cholesterol, triglyceride and LDL cholesterol. Fisetin also effectively mitigated HFD-induced oxidative stress and inflammation in mice. Hepatic lipidomics revealed significant alterations in lipid content and composition following fisetin treatment, including reductions in lipids associated with AS risk, such as cholesteryl ester (ChE), phosphatidylcholines (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), cardiolipin (CL), phosphatidylinositol (PI), and TG. Additionally, phosphatidylserine (PS) levels were increased. RNA sequencing of livers revealed that fisetin affected genes related to cholesterol metabolism and bile acid biosynthesis, including cytochrome P450 ( Cyp ) family and Nr1h4 ( Fxr ). Molecular docking analysis suggested FXR may be a potential target of fisetin. In the liver, cholesterol can be either converted into bile acids or pumped out to bile ducts by ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) for elimination. Fisetin treatment notably modulated the hepatic proteins related to cholesterol metabolism (HMGCR, PCSK9, LDLR, FXR, CYP27A1, CYP7A1, CYP8B1 and BSEP) and cholesterol excretion (ABCG5, ABCG8), maintaining cholesterol homeostasis. Additionally, fisetin increased the excretion of fecal neutral sterols, including cholesterol, dihydrocholesterol, and coprosterone. It also increased the expression of FXR, ABCG5, ABCG8, and LDLR, while decreasing NPC1L1 and PCSK9 levels in the jejunum, thereby stimulating the TICE pathway. These findings provide compelling evidence that fisetin reduces cholesterol levels and alleviates AS by stimulating FXR-mediated hepatic cholesterol metabolism and the TICE pathway. The findings suggest that fisetin-regulated cholesterol metabolism may represent a promising therapeutic strategy for the treatment of AS.
研究领域:
药理学
·
心血管医学
·
生物化学
·
分子生物学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）