scholarly journals Lactobacillus delbrueckii Interfere With Bile Acid Enterohepatic Circulation to Regulate Cholesterol Metabolism of Growing–Finishing Pigs via Its Bile Salt Hydrolase Activity

2020 ◽  
Vol 7 ◽  
Author(s):  
Gaifeng Hou ◽  
Wei Peng ◽  
Liangkai Wei ◽  
Rui Li ◽  
Yong Yuan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
Lactobacillus Delbrueckii ◽  
Farnesoid X Receptor ◽  
Bile Salt Hydrolase ◽  
Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn–soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii–fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut–liver FXR–FGF19 axis.

Bile Acids: The Good, the Bad, and the Ugly

Physiology ◽  
1999 ◽  
Vol 14 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Alan F. Hofmann
Keyword(s):  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Absorption ◽  
Bile Acid Metabolism ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor

Bile acids, amphipathic end products of cholesterol metabolism, are “good” in the infant because they enhance lipid absorption and thereby promote growth. Bile acids also induce bile flow and biliary lipid secretion. The enterohepatic circulation of bile acids is “bad” in the adult because it downregulates hepatocyte low-density lipoprotein receptor activity and thereby elevates plasma cholesterol levels. Defects in bile acid metabolism such as impaired biosynthesis or transport are “ugly” because they cause morbidity and death. New approaches for treating these defects are being developed.

scholarly journals Macrophage LRP1 Promotes Diet-Induced Hepatic Inflammation and Metabolic Dysfunction by Modulating Wnt Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Dianaly T. Au ◽  
Mary Migliorini ◽  
Dudley K. Strickland ◽  
Selen C. Muratoglu
Keyword(s):  
Insulin Resistance ◽  
Wnt Signaling ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Hepatic Inflammation ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

Hepatic inflammation is associated with the development of insulin resistance, which can perpetuate the disease state and may increase the risk of metabolic syndrome and diabetes. Despite recent advances, mechanisms linking hepatic inflammation and insulin resistance are still unclear. The low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is highly expressed in macrophages, adipocytes, hepatocytes, and vascular smooth muscle cells. To investigate the potential role of macrophage LRP1 in hepatic inflammation and insulin resistance, we conducted experiments using macrophage-specific LRP1-deficient mice (macLRP1−/−) generated on a low-density lipoprotein receptor knockout (LDLR−/−) background and fed a Western diet. LDLR−/−; macLRP1−/− mice gained less body weight and had improved glucose tolerance compared to LDLR−/− mice. Livers from LDLR−/−; macLRP1−/− mice displayed lower levels of gene expression for several inflammatory cytokines, including Ccl3, Ccl4, Ccl8, Ccr1, Ccr2, Cxcl9, and Tnf, and reduced phosphorylation of GSK3α and p38 MAPK proteins. Furthermore, LRP1-deficient peritoneal macrophages displayed altered cholesterol metabolism. Finally, circulating levels of sFRP-5, a potent anti-inflammatory adipokine that functions as a decoy receptor for Wnt5a, were elevated in LDLR−/−; macLRP1−/− mice. Surface plasmon resonance experiments revealed that sFRP-5 is a novel high affinity ligand for LRP1, revealing that LRP1 regulates levels of this inhibitor of Wnt5a-mediated signaling. Collectively, our results suggest that LRP1 expression in macrophages promotes hepatic inflammation and the development of glucose intolerance and insulin resistance by modulating Wnt signaling.

scholarly journals Effects of alfalfa saponin extract on the performance and cholesterol metabolism of laying hens

2015 ◽  
Author(s):  
Senhao Zhang ◽  
Yinghua Shi ◽  
Minggen Liang ◽  
Jia Li ◽  
Chengzhang Wang
Keyword(s):  
Bile Acid ◽  
Mrna Expression ◽  
Laying Hens ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Mrna Levels ◽  
Density Lipoprotein Receptor ◽  
Yolk Cholesterol

The experiment was performed to determine the effects of alfalfa saponin extract (ASE) on the performance and cholesterol metabolism of laying hens. A total of 150 Hy-Line Brown hens with 28 weeks old, were randomly divided into five treatment groups (five replicates per treatment with six hens per replicate). Diets containing 0, 60, 120, 240, and 480 mg ASE/kg were fed to hens for 77 days. The shell thickness had a trend to increase. The yolk cholesterol and liver bile acid decreased significantly (ASE 60 and 480 mg/kg groups for yolk cholesterol, and ASE 60 and 240 mg/kg groups for liver bile acid). Fecal bile acid has an elevation trend as ASE increased. The expression of very low density apolipoprotein-Ⅱ (apoVLDL-Ⅱ) gene was not affected by adding ASE. However, the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene and cholesterol 7α-hydroxylase (CYP7A1) gene were significantly up-regulated. The mRNA expression of very-low-density-lipoprotein receptor(VLDLR) gene was suppressed due to adding ASE supplementation in the diet. These findings indicated that dietary ASE could regulate cholesterol levels in hens by up-regulating the mRNA levels of HMG-CoA and CYP7A1 and suppressing the expression of VLDLR.

scholarly journals Effects of alfalfa saponin extract on the performance and cholesterol metabolism of laying hens

2015 ◽  
Author(s):  
Senhao Zhang ◽  
Yinghua Shi ◽  
Minggen Liang ◽  
Jia Li ◽  
Chengzhang Wang
Keyword(s):  
Bile Acid ◽  
Mrna Expression ◽  
Laying Hens ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Mrna Levels ◽  
Density Lipoprotein Receptor ◽  
Yolk Cholesterol

The experiment was performed to determine the effects of alfalfa saponin extract (ASE) on the performance and cholesterol metabolism of laying hens. A total of 150 Hy-Line Brown hens with 28 weeks old, were randomly divided into five treatment groups (five replicates per treatment with six hens per replicate). Diets containing 0, 60, 120, 240, and 480 mg ASE/kg were fed to hens for 77 days. The shell thickness had a trend to increase. The yolk cholesterol and liver bile acid decreased significantly (ASE 60 and 480 mg/kg groups for yolk cholesterol, and ASE 60 and 240 mg/kg groups for liver bile acid). Fecal bile acid has an elevation trend as ASE increased. The expression of very low density apolipoprotein-Ⅱ (apoVLDL-Ⅱ) gene was not affected by adding ASE. However, the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene and cholesterol 7α-hydroxylase (CYP7A1) gene were significantly up-regulated. The mRNA expression of very-low-density-lipoprotein receptor(VLDLR) gene was suppressed due to adding ASE supplementation in the diet. These findings indicated that dietary ASE could regulate cholesterol levels in hens by up-regulating the mRNA levels of HMG-CoA and CYP7A1 and suppressing the expression of VLDLR.

scholarly journals Two Weeks Of Western Diet Disrupts Liver Molecular Markers Of Cholesterol Metabolism In Rat

2020 ◽  
Author(s):  
Roxane St-Amand ◽  
Emilienne T. Ngo Sock ◽  
Samantha Quinn ◽  
Jean-Marc Lavoie ◽  
David H. St-Pierre
Keyword(s):  
Total Cholesterol ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Plasma Total Cholesterol ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor ◽  
Element Binding Protein

Abstract Background: The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method: Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results: Weight gain (~ 40g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.

scholarly journals The Roles of Low-Density Lipoprotein Receptor-Related Proteins 5, 6, and 8 in Cancer: A Review

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Zulaika Roslan ◽  
Mudiana Muhamad ◽  
Lakshmi Selvaratnam ◽  
Sharaniza Ab-Rahim
Keyword(s):  
Cancer Progression ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lung Squamous Cell Carcinoma ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Cell Functions ◽  
Density Lipoprotein Receptor

Low-density lipoprotein receptor (LDLR) has been an object of research since the 1970s because of its role in various cell functions. The LDLR family members include LRP5, LRP6, and LRP8. Even though LRP5, 6, and 8 are in the same family, intriguingly, these three proteins have various roles in physiological events, as well as in regulating different mechanisms in various kinds of cancers. LRP5, LRP6, and LRP8 have been shown to play important roles in a broad panel of cancers. LRP5 is highly expressed in many tissues and is involved in the modulation of glucose-induced insulin secretion, bone development, and cholesterol metabolism, as well as cancer progression. Recently, LRP5 has also been shown to play a role in chondroblastic subtype of osteosarcoma (OS) and prostate cancer and also in noncancer case such as osteoporosis. LRP6, which has been previously discovered to share the same structures as LRP5, has also been associated with many cancer progressions such as human triple negative breast cancer (TNBC), primary chronic lymphocytic leukemia (CLL), nonsmall cell lung cancer (NSCL), lung squamous cell carcinoma (LSCC), and hepatocellular carcinoma (HCC). In addition to its role in cancer progression, LRP8 (apolipoprotein E receptor 2 [APOER2]) has also been demonstrated to regulate canonical Wnt/β-catenin signaling pathway whereby this pathway plays a role in cell migration and development. Therefore, this review aimed to elucidate the role of LRP 5, 6, and 8 in regulating the cancer progression.

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