Regulation of genes related to cholesterol metabolism in rainbow trout (Oncorhynchus mykiss) fed a plant-based diet

When compared with fish meal and fish oil, plant ingredients differ not only in their protein content and amino acid and fatty acid profiles but are also devoid of cholesterol, the major component of cell membrane and precursor of several bioactive compounds. Based on these nutritional characteristics, plant-based diets can affect fish physiology and cholesterol metabolism. To investigate the mechanisms underlying cholesterol homeostasis, rainbow trout were fed from 1 g body wt for 6 mo with a totally plant-based diet (V), a marine diet (M), and a marine-restricted diet (MR), with feed intake adjusted to that of the V group. The expression of genes involved in cholesterol synthesis, esterification, excretion, bile acid synthesis, and cholesterol efflux was measured in liver. Results showed that genes involved in cholesterol synthesis were upregulated in trout fed the V diet, whereas expression of genes related to bile acid synthesis ( cyp7a1) and cholesterol elimination ( abcg8) were reduced. Feeding trout the V diet also enhanced the expression of srebp-2 while reducing that of lxrα and miR-223. Overall, these data suggested that rainbow trout coped with the altered nutritional characteristics and absence of dietary cholesterol supply by increasing cholesterol synthesis and limiting cholesterol efflux through molecular mechanisms involving at least srebp-2, lxrα, and miR-223. However, plasma and body cholesterol levels in trout fed the V diet were lower than in fish fed the M diet, raising the question of the role of cholesterol in the negative effect of plant-based diet on growth.

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Changes in Cholesterol Metabolism with Dietary Cholesterol in Children with Familial Hypercholesterolaemia

Clinical Science ◽

10.1042/cs0560377 ◽

1979 ◽

Vol 56 (4) ◽

pp. 377-380 ◽

Cited By ~ 18

Author(s):

Gillian M. Martin ◽

P. Nestel

Keyword(s):

Bile Acid ◽

Healthy Subjects ◽

Cholesterol Synthesis ◽

Familial Hypercholesterolaemia ◽

Cholesterol Metabolism ◽

Plasma Cholesterol ◽

Dietary Cholesterol ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Healthy Children

1. Possible defects in cholesterol metabolism were sought in children with familial hypercholesterolaemia. 2. In nine affected children (eight heterozygotes and one homozygote) and in five healthy children, cholesterol synthesis and bile acid synthesis were determined from the excretion of steroids in the faeces during a low cholesterol diet. Cholesterol synthesis of 10·1 ± 4·4 mg day−1 kg−1 in the hypercholesterolaemic children was similar to that in these and other normal children. Mean bile acid synthesis of 4·0 ± 2·1 mg day−1 kg−1 also resembled normal values though three severely affected heterozygotes excreted substantially less. 3. The response to 4 weeks' additional 450 mg of dietary cholesterol/day led to variable changes in the plasma cholesterol and in the sterol balance. On average the affected children showed a rise in plasma cholesterol which resembled that in healthy subjects. The sterol balance fell in most, suggesting a reduction in cholesterol synthesis, which is the normal response to dietary cholesterol. 4. The response to dietary cholesterol was therefore at least qualitatively similar in the hypercholesterolaemic children to that reported in healthy subjects.

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Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22147451 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7451

Author(s):

Harpreet Kaur ◽

Drew Seeger ◽

Svetlana Golovko ◽

Mikhail Golovko ◽

Colin Kelly Combs

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Bile Acid ◽

Bile Acids ◽

Cholesterol Metabolism ◽

Amyloid Β ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Liver Cholesterol ◽

Bile Acid Metabolism

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

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Effect of type of dietary non‐protein energy source (starch vs. fat) on the body bile acid pool size and composition, faecal bile acid loss and bile acid synthesis in rainbow trout ( Oncorhynchus mykiss )

Aquaculture Nutrition ◽

10.1111/anu.13231 ◽

2021 ◽

Author(s):

Thomas W. O. Staessen ◽

Marc C. J. Verdegem ◽

Marit A. J. Nederlof ◽

Ep H. Eding ◽

Johan W. Schrama

Keyword(s):

Energy Source ◽

Rainbow Trout ◽

Bile Acid ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

The Body ◽

Bile Acid Pool ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Protein Energy ◽

Bile Acid Pool Size

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Regulation of Bile Acid and Cholesterol Metabolism by PPARs

PPAR Research ◽

10.1155/2009/501739 ◽

2009 ◽

Vol 2009 ◽

pp. 1-15 ◽

Cited By ~ 65

Author(s):

Tiangang Li ◽

John Y. L. Chiang

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Cholesterol Metabolism ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Cholesterol Homeostasis ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Major Pathway ◽

Therapeutic Implications

Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ) regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARαalters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.

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Abstract 49: The Transcriptional Repressor MafG Regulates Cholesterol Catabolism

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.49 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Thomas Q de Aguiar Vallim ◽

Elizabeth J Tarling ◽

Hannah Ahn ◽

Lee R Hagey ◽

Casey E Romanoski ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Acid Metabolism ◽

Metabolic Diseases ◽

Cholesterol Metabolism ◽

Transcriptional Repressor ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Bile Acid Metabolism ◽

Biliary Bile Acid

Elevated circulating cholesterol levels is a major risk factor for cardiovascular diseases (CVD), and therefore understanding pathways that affect cholesterol metabolism are important for potential treatment of CVD. The major route for cholesterol excretion is through its catabolism to bile acids. Specific bile acids are also potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis ( Cyp7a1 , Cyp8b1 ) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway, and modifies the biliary bile acid composition. In contrast, MafG loss-of-function studies cause de-repression of the bile acid genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-Seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR. The identification of this pathway will likely have important implications in metabolic diseases.

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Intestine-Specific Overexpression of LDLR Enhances Cholesterol Excretion and Induces Metabolic Changes in Male Mice

Endocrinology ◽

10.1210/en.2018-00098 ◽

2018 ◽

Vol 160 (4) ◽

pp. 744-758 ◽

Cited By ~ 1

Author(s):

Luca Meoli ◽

Danny Ben-Zvi ◽

Courtney Panciotti ◽

Stephanie Kvas ◽

Palmenia Pizarro ◽

...

Keyword(s):

Molecular Mechanisms ◽

Cholesterol Metabolism ◽

Treatment Options ◽

Density Lipoprotein ◽

Cholesterol Absorption ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Metabolic Effects ◽

Cholesterol Levels ◽

Cholesterol Excretion

Abstract Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatment options for severe obesity and related comorbidities, including hyperlipidemia, a well-established risk factor of cardiovascular diseases. Elucidating the molecular mechanisms underlying the beneficial effects of RYGB may facilitate development of equally effective, but less invasive, treatments. Recent studies have revealed that RYGB increases low-density lipoprotein receptor (LDLR) expression in the intestine of rodents. Therefore, in this study we first examined the effects of RYGB on intestinal cholesterol metabolism in human patients, and we show that they also exhibit profound changes and increased LDLR expression. We then hypothesized that the upregulation of intestinal LDLR may be sufficient to decrease circulating cholesterol levels. To this end, we generated and studied mice that overexpress human LDLR specifically in the intestine. This perturbation significantly affected intestinal metabolism, augmented fecal cholesterol excretion, and induced a reciprocal suppression of the machinery related to luminal cholesterol absorption and bile acid synthesis. Circulating cholesterol levels were significantly decreased and, remarkably, several other metabolic effects were similar to those observed in RYGB-treated rodents and patients, including improved glucose metabolism. These data highlight the importance of intestinal cholesterol metabolism for the beneficial metabolic effects of RYGB and for the treatment of hyperlipidemia.

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