scholarly journals Infant Formula Feeding Increases Hepatic Cholesterol 7α Hydroxylase (CYP7A1) Expression and Fecal Bile Acid Loss in Neonatal Piglets

2018 ◽  
Vol 148 (5) ◽  
pp. 702-711 ◽  
Author(s):  
Kelly E Mercer ◽  
Sudeepa Bhattacharyya ◽  
Maria Elena Diaz-Rubio ◽  
Brian D Piccolo ◽  
Lindsay M Pack ◽  
...  
Keyword(s):  
Bile Acid ◽  
Protein Expression ◽  
Enterohepatic Circulation ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Formula Feeding ◽  
Infant Formulas ◽  
Fecal Bile Acid ◽  
Hepatic Cholesterol ◽  
Neonatal Piglets

Abstract Background During the postnatal feeding period, formula-fed infants have higher cholesterol synthesis rates and lower circulating cholesterol concentrations than their breastfed counterparts. Although this disparity has been attributed to the uniformly low dietary cholesterol content of typical infant formulas, little is known of the underlying mechanisms associated with this altered cholesterol metabolism phenotype. Objective We aimed to determine the molecular etiology of diet-associated changes in early-life cholesterol metabolism with the use of a postnatal piglet feeding model. Methods Two-day-old male and female White-Dutch Landrace piglets were fed either sow milk (Sow group) or dairy-based (Milk group; Similac Advance powder) or soy-based (Soy group; Emfamil Prosobee Lipil powder) infant formulas until day 21. In addition to measuring serum cholesterol concentrations, hepatic and intestinal genes involved in enterohepatic circulation of cholesterol and bile acids were analyzed by real-time reverse-transcriptase polymerase chain reaction and Western blot. Bile acid concentrations were measured by liquid chromatography–mass spectrometry in serum, liver, and feces. Results Compared with the Sow group, hepatic cholesterol 7α hydroxylase (CYP7A1) protein expression was 3-fold higher in the Milk group (P < 0.05) and expression was 10-fold higher in the Soy group compared with the Milk group (P < 0.05). Likewise, fecal bile acid concentrations were 3-fold higher in the Soy group compared with the Milk group (P < 0.05). Intestinal mRNA expression of fibroblast factor 19 (Fgf19) was reduced in the Milk and Soy groups, corresponding to 54% and 67% decreases compared with the Sow group. In the Soy group, small heterodimer protein (SHP) protein expression was 30% lower compared with the Sow group (P < 0.05). Conclusions These results indicate that formula feeding leads to increased CYP7A1 protein expression and fecal bile acid loss in neonatal piglets, and this outcome is linked to reduced efficacy in inhibiting CYP7A1 expression through FGF19 and SHP transcriptional repression mechanisms.

Cholesterol metabolism. II. Quantitative measurement of cholesterol absorption

1965 ◽  
Vol 20 (3) ◽  
pp. 538-541 ◽  
Author(s):  
Daniel K. Bloomfield
Keyword(s):  
Bile Acid ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Cholesterol Absorption ◽  
Fecal Bile Acid ◽  
Fecal Bile Acids ◽  
Human Use ◽  
The Difference ◽  
Sterol Excretion ◽  
Physiological Method

A simple physiological method for quantitative study of cholesterol absorption is presented. The method uses the fecal bile acid tracer of dietary cholesterol-4-C14 as an index of cholesterol that has been absorbed, metabolized, and re-excreted. Since the fecal bile acid-to-sterol excretion ratio for rats on any specific diet is constant and can be measured, endogenous excretion of sterol can be calculated from bile acid values. Nonabsorbed sterol is the difference between total fecal sterol and endogenously excreted sterol. Although the method is described in rats, it is independent of species and is probably suitable for human use. endogenous sterol excretion; fecal bile acids and steroids Submitted on August 20, 1964

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.

scholarly journals Short- and long-term effects of biliary drainage on hepatic cholesterol metabolism in the rat

1990 ◽  
Vol 269 (3) ◽  
pp. 781-788 ◽  
Author(s):  
M J Smit ◽  
A M Temmerman ◽  
R Havinga ◽  
F Kuipers ◽  
R J Vonk
Keyword(s):  
Bile Acid ◽  
Bile Flow ◽  
Cholesterol Metabolism ◽  
Acid Output ◽  
Biliary Secretion ◽  
Surgical Trauma ◽  
Hepatic Cholesterol ◽  
Long Term Effects ◽  
Short And Long Term

The present study concerns short- and long-term effects of interruption of the enterohepatic circulation (EHC) on hepatic cholesterol metabolism and biliary secretion in rats. For this purpose, we employed a technique that allows reversible interruption of the EHC, during normal feeding conditions, and excludes effects of anaesthesia and surgical trauma. [3H]Cholesteryl oleate-labelled human low-density lipoprotein (LDL) was injected intravenously in rats with (1) chronically (8 days) interrupted EHC, (2) interrupted EHC at the time of LDL injection and (3) intact EHC. During the first 3 h after interruption of the EHC, bile flow decreased to 50% and biliary bile acid, phospholipid and cholesterol secretion to 5%, 11% and 19% of their initial values respectively. After 8 days of bile diversion, biliary cholesterol output and bile flow were at that same level, but bile acid output was increased 2-3-fold and phospholipid output was about 2 times lower. The total amount of cholesterol in the liver decreased after interruption of the EHC, which was mainly due to a decrease in the amount of cholesteryl ester. Plasma disappearance of LDL was not affected by interruption of the EHC. Biliary secretion of LDL-derived radioactivity occurred 2-4 times faster in chronically interrupted rats as compared with the excretion immediately after interruption of the EHC. Radioactivity was mainly in the form of bile acids under both conditions. This study demonstrates the very rapid changes that occur in cholesterol metabolism and biliary lipid composition after interruption of the EHC. These changes must be taken into account in studies concerning hepatic metabolism of lipoprotein cholesterol and subsequent secretion into bile.

Abstract 329: HSF-1 Knockout Enhances Dietary Cholesterol Metabolism by Inducing CYP7A1 Gene Expression and Attenuates Atherosclerosis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Govindasamy Ilangovan ◽  
Krishnamurthy Karthikeyan
Keyword(s):  
Heart Disease ◽  
Bile Acid ◽  
Heat Shock ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Atherosclerotic Lesion ◽  
Heat Shock Factor 1 ◽  
Mrna Levels ◽  
Gene Promoters ◽  
Gene Expressions

Objective: Coronary heart disease and diabetes are highly prevalent among obese populations due to aberrant dietary cholesterol metabolism. Here we investigated the effect of heat shock factor-1 (HSF-1) on atherosclerosis and dietary cholesterol metabolism. Methods and Results: Atherogenic western diet-induced weight gain was reduced in HSF-1 and LDLr double knock out mice (HSF-1 -/- /LDLr -/- ), compared to LDLr -/- mice. Atherosclerotic lesion growth in aortic arch and carotid regions was retarded. Also, repression of PPAR-γ2 and AMPKα expression in adipose tissue, low hepatic steatosis, and lessened plasma adiponectins and lipoproteins were observed. Furthermore, reduced heat shock proteins and their mRNA levels in atherosclerotic lesions correlated with reduction in lesion burden. In HSF-1 -/- /LDLr -/- liver, higher cholesterol 7α hydroxylase (CYP7A1, the rate limiting enzyme in the synthesis of bile acid from cholesterol) and MDR1/p-glycoprotein (bile salt transporter across the hepatocyte canalicular membrane) gene expressions were observed, consistent with higher bile acid sequestration and larger hepatic bile ducts. HSF-1 deletion, however, upregulated both CYP7A1 enzyme and MDR1/p-glycoportein expression and activities, due to removal of its repressive binding in the CYP7A1 and MDR1 gene promoters. This increased the conversion of cholesterol into 7-α-hydroxycholesterol and bile acid, and dietary cholesterol metabolism. Conclusions: HSF-1 ablation not only eliminates heat shock response to retard atherosclerosis, but it also transcriptionally upregulates CYP7A1 and MDR1/P-gp axis to increase cholesterol metabolism. Therefore, HSF-1 is a metabolic regulator of dietary cholesterol and a major contributor to heart disease among obese population.

Abstract 65: Flavin Monoxygenase 3 (FMO3) is a Novel Regulator of Hepatic Cholesterol Metabolism and Transintestinal Cholesterol Efflux (TICE).

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Manya Warrier ◽  
Stepahie Marshall ◽  
Allison McDaniel ◽  
Martha Wilson ◽  
Amanda Brown ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Plasma Levels ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Transcriptional Profiling ◽  
Dietary Cholesterol ◽  
High Cholesterol Diet ◽  
Hepatic Cholesterol ◽  
Hepatic Expression ◽  
Cholesterol Levels

Recent studies have revealed a novel route for cholesterol disposal through intestine known as transintestinal cholesterol efflux (TICE) that significantly contributes to fecal neutral sterol loss. This pathway is an integral part of reverse cholesterol transport (RCT), yet major mechanisms regulating TICE are not well understood. Using an unbiased transcriptional profiling approach in mouse models of augmented TICE, we found that hepatic expression of the enzyme Flavin monoxygenase 3 (FMO3) was dramatically repressed. At the same time we identified this enzyme through transcriptional profiling, it was reported that plasma levels of its product trimethylamineoxide (TMAO) are highly predictive of atheroslcerosis in humans, and TMAO is proatherogenic in mice. To further understand FMO3’s role as a regulator of cholesterol metabolism we used antisense oligonucleotides (ASO) to knockdown FMO3 expression in mouse liver in C57BL/6 mice fed either low (0.02%) or high (0.2%) levels of dietary cholesterol. As expected, FMO3 knockdown (>90% knockdown in the liver) increased the TMA/TMAO ratio in plasma more than 3-fold. Interestingly, knockdown of FMO biliary cholesterol levels were reduced by 60%, whereas fecal cholesterol loss was quite normal in FMO3 ASO treated mice fed a high cholesterol diet, which phenocopies a previously described mouse model where TICE predominates (NPC1L1-liver transgenic mice). ASO-mediated knockdown of FMO3 also unexpectedly reduced hepatic cholesteryl ester (CE) storage by 70% in mice fed 0.2% cholesterol. In parallel, knockdown of FMO3 reduces plasma VLDL cholesterol levels and the secretion rate of VLDL cholesteryl ester, but not triacylglycerol in cholesterol fed mice. FMO3 knockdown also reduced the hepatic expression of several liver X receptor (LXR) target genes, while increasing expression of genes involved in cholesterol synthesis. Collectively, these studies have identified FMO3 as a novel regulator of hepatic cholesterol metabolism and TICE. Given that plasma levels of FMO3’s product (TMAO) are strongly associated with atherosclerosis development in humans, and production of TMAO promotes atherosclerosis in mice, these studies have important implications for future cardiovascular drug discovery.

scholarly journals Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRβ-deficient mice

2001 ◽  
Vol 107 (5) ◽  
pp. 565-573 ◽  
Author(s):  
S. Alberti ◽  
G. Schuster ◽  
P. Parini ◽  
D. Feltkamp ◽  
U. Diczfalusy ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Hepatic Cholesterol ◽  
Deficient Mice

Niemann-Pick C2 Protein Expression Regulates Lithogenic Diet-Induced Gallstone Formation and Dietary Cholesterol Metabolism in Mice

Lipids ◽  
2011 ◽  
Vol 47 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Elisa Balboa ◽  
Gabriela Morales ◽  
Paula Aylwin ◽  
Gonzalo Carrasco ◽  
Ludwig Amigo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Gallstone Formation ◽  
Lithogenic Diet ◽  
Niemann Pick

scholarly journals The Role of Bile Acid Excretion in Atherosclerotic Coronary Artery Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Gideon Charach ◽  
Alexander Rabinovich ◽  
Ori Argov ◽  
Moshe Weintraub ◽  
Pavel Rabinovich
Keyword(s):  
Coronary Artery Disease ◽  
Bile Acid ◽  
Coronary Artery ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Artery Disease ◽  
Bile Excretion ◽  
The Impact ◽  
Fractional Absorption

The impact of cholesterol and different classes of lipoproteins on the development of coronary artery disease (CAD) has been investigated in extensively during the past 50 years. The cholesterol metabolism is dependent on numerous factors, including dietary fat, fractional absorption of dietary cholesterol, tissue stores of cholesterol, endogenous cholesterol synthesis, and fecal bile excretion. Several studies showed significantly lower amounts of bile acid secretion in adult patients with CAD compared to non-CAD patients. Could it be that the inability to efficiently excrete bile acids may lead to CAD development?

scholarly journals Dietary Betaine Addition Promotes Hepatic Cholesterol Synthesis, Bile Acid Conversion, and Export in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1399
Author(s):  
Sisi Li ◽  
Shuyi Xu ◽  
Yang Zhao ◽  
Haichao Wang ◽  
Jie Feng
Keyword(s):  
Bile Acid ◽  
High Fat Diet ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Basal Diet ◽  
Hepatic Cholesterol ◽  
Sprague Dawley ◽  
High Fat

It is widely reported how betaine addition regulates lipid metabolism but how betaine affects cholesterol metabolism is still unknown. This study aimed to investigate the role of betaine in hepatic cholesterol metabolism of Sprague-Dawley rats. Rats were randomly allocated to four groups and fed with a basal diet or a high-fat diet with or without 1% betaine. The experiment lasted 28 days. The results showed that dietary betaine supplementation reduced the feed intake of rats with final weight unchanged. Serum low-density-lipoprotein cholesterol was increased with the high-fat diet. The high-fat diet promoted cholesterol synthesis and excretion by enhancing the HMG-CoA reductase and ABCG5/G8, respectively, which lead to a balance of hepatic cholesterol. Rats in betaine groups showed a higher level of hepatic total cholesterol. Dietary betaine addition enhanced cholesterol synthesis as well as conversion of bile acid from cholesterol by increasing the levels of HMGCR and CYP7A1. The high-fat diet decreased the level of bile salt export pump, while dietary betaine addition inhibited this decrease and promoted bile acid efflux and increased total bile acid levels in the intestine. In summary, dietary betaine addition promoted hepatic cholesterol metabolism, including cholesterol synthesis, conversion of bile acids, and bile acid export.

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