The role of diet during development on the regulation of adult cholesterol homeostasis

1985 ◽  
Vol 63 (5) ◽  
pp. 557-564 ◽  
Author(s):  
Sheila M. Innis
Keyword(s):  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Cholesterol Homeostasis ◽  
Cholesterol Levels ◽  
Effective Training ◽  
Cholesterol Intake ◽  
Lower Plasma Cholesterol ◽  
Altered Metabolism

Atherosclerosis is believed to begin early in life and to develop over several decades. Elevated plasma cholesterol is a major contributing factor. Studies in animals have shown that manipulation of cholesterol metabolism during its development in pre-and early post-natal life can permanently alter cholesterol synthesis and catabolism to favour lower plasma cholesterol levels in the adult faced with a high dietary cholesterol intake. Although the mechanisms and pathways involved are likely to be different, "metabolic training" can occur as a result of both the diet fed to the mother during gestation and lactation and from the diet fed to the animal itself in early life. The presence of cholesterol itself in the suckling diet does not appear to confer any lasting improvement to cholesterol handling in either man or animals. Although much research is still required to define the time in development for effective training of specific steps in cholesterol metabolism and the primary site and mechanism of permanently altered metabolism, significant progress has been made. These studies will form the basis of this review.

scholarly journals Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Vijay R. Varma ◽  
H. Büşra Lüleci ◽  
Anup M. Oommen ◽  
Sudhir Varma ◽  
Chad T. Blackshear ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
Transcriptomic Data ◽  
Brain Cholesterol ◽  
Cholesterol Levels

AbstractThe role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson’s disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.

scholarly journals Genetic susceptibility, dietary cholesterol intake, and plasma cholesterol levels in a Chinese population

2020 ◽  
Vol 61 (11) ◽  
pp. 1504-1511
Author(s):  
Shaofeng Huo ◽  
Liang Sun ◽  
Geng Zong ◽  
Boyu Song ◽  
He Zheng ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Chinese Population ◽  
Plasma Cholesterol ◽  
Nutrition Transition ◽  
Dietary Cholesterol ◽  
Effect Sizes ◽  
Risk Scores ◽  
Asian Countries ◽  
Cholesterol Levels ◽  
Cholesterol Intake

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRSTC, 57 SNPs), LDL-C (GRSLDL-C, 45 SNPs), and HDL-C (GRSHDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRSTC (effect sizes: −0.29, 0.34, 2.45, and 6.47; Pinteraction = 0.002) and GRSLDL-C (effect sizes: −1.35, 0.17, 5.45, and 6.07; Pinteraction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRSTC (Pinteraction = 0.001) and GRSLDL-C (Pinteraction = 0.004). The adverse effects of GRSTC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; Pinteraction = 0.023) and GRSLDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; Pinteraction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.

scholarly journals Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence

2020 ◽  
Vol 22 (1) ◽  
pp. 227
Author(s):  
Giusy Rita Caponio ◽  
David Q.-H. Wang ◽  
Agostino Di Ciaula ◽  
Maria De Angelis ◽  
Piero Portincasa
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Medicine ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Soy Proteins ◽  
Dietary Recommendations ◽  
Pharmacological Interventions ◽  
Cholesterol Levels ◽  
Important Amount

Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.

scholarly journals Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease

2018 ◽  
Vol 19 (11) ◽  
pp. 3426 ◽  
Author(s):  
Asier Benito-Vicente ◽  
Kepa Uribe ◽  
Shifa Jebari ◽  
Unai Galicia-Garcia ◽  
Helena Ostolaza ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Cholesterol Homeostasis ◽  
Hereditary Diseases ◽  
Special Focus ◽  
Peripheral Tissues ◽  
Premature Cardiovascular Disease

Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. For this reason, cholesterol metabolism must be tightly controlled. Cell cholesterol is mainly acquired from two sources: Dietary cholesterol, which is absorbed in the intestine and, intracellularly synthesized cholesterol that is mainly synthesized in the liver. Once acquired, both are delivered to peripheral tissues in a lipoprotein dependent mechanism. Malfunctioning of cholesterol metabolism is caused by multiple hereditary diseases, including Familial Hypercholesterolemia, Sitosterolemia Type C and Niemann-Pick Type C1. Of these, familial hypercholesterolemia (FH) is a common inherited autosomal co-dominant disorder characterized by high plasma cholesterol levels. Its frequency is estimated to be 1:200 and, if untreated, increases the risk of premature cardiovascular disease. This review aims to summarize the current knowledge on cholesterol metabolism and the relation of FH to cholesterol homeostasis with special focus on the genetics, diagnosis and treatment.

scholarly journals Diet-Induced Metabolic Improvements in a Hamster Model of Hypercholesterolemia Are Strongly Linked to Alterations of the Gut Microbiota

2009 ◽  
Vol 75 (12) ◽  
pp. 4175-4184 ◽  
Author(s):  
Inés Martínez ◽  
Grant Wallace ◽  
Chaomei Zhang ◽  
Ryan Legge ◽  
Andrew K. Benson ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Intervention ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Positive Association ◽  
Cholesterol Homeostasis ◽  
Gastrointestinal Microbiota ◽  
Hamster Model ◽  
Cholesterol Levels

ABSTRACT The mammalian gastrointestinal microbiota exerts a strong influence on host lipid and cholesterol metabolism. In this study, we have characterized the interplay among diet, gut microbial ecology, and cholesterol metabolism in a hamster model of hypercholesterolemia. Previous work in this model had shown that grain sorghum lipid extract (GSL) included in the diet significantly improved the high-density lipoprotein (HDL)/non-HDL cholesterol equilibrium (T. P. Carr, C. L. Weller, V. L. Schlegel, S. L. Cuppett, D. M. Guderian, Jr., and K. R. Johnson, J. Nutr. 135:2236-2240, 2005). Molecular analysis of the hamsters' fecal bacterial populations by pyrosequencing of 16S rRNA tags, PCR-denaturing gradient gel electrophoresis, and Bifidobacterium-specific quantitative real-time PCR revealed that the improvements in cholesterol homeostasis induced through feeding the hamsters GSL were strongly associated with alterations of the gut microbiota. Bifidobacteria, which significantly increased in abundance in hamsters fed GSL, showed a strong positive association with HDL plasma cholesterol levels (r = 0.75; P = 0.001). The proportion of members of the family Coriobacteriaceae decreased when the hamsters were fed GSL and showed a high positive association with non-HDL plasma cholesterol levels (r = 0.84; P = 0.0002). These correlations were more significant than those between daily GSL intake and animal metabolic markers, implying that the dietary effects on host cholesterol metabolism are conferred, at least in part, through an effect on the gut microbiota. This study provides evidence that modulation of the gut microbiota-host metabolic interrelationship by dietary intervention has the potential to improve mammalian cholesterol homeostasis, which has relevance for cardiovascular health.

scholarly journals Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Claudia Villani ◽  
Giuseppina Sacchetti ◽  
Renzo Bagnati ◽  
Alice Passoni ◽  
Federica Fusco ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Potential Role ◽  
Cholesterol Metabolism ◽  
Cholesterol Homeostasis ◽  
Motor Deficits ◽  
Brain Cholesterol ◽  
Background Strain ◽  
Cholesterol Levels ◽  
The Brain

Previous studies provided evidence for the alteration of brain cholesterol homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The efficacy of statins in improving motor symptoms and prolonging survival of mutant mice suggested a potential role of statins in the therapy of Rett syndrome. In the present study, we show that Mecp2 deletion had no effect on brain and reduced serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the previous study) had no effects on motor deficits and survival when Mecp2 deletion was expressed on a background strain (C57BL/6J; B6) differing from that used in the earlier study. These findings indicate that the effects of statins may be background specific and raise important issues to consider when contemplating clinical trials. The reduction of the brain cholesterol metabolite 24S-hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence of changes in brain cholesterol metabolism and the potential utility of using plasma levels of 24S-OHC as a biomarker of brain cholesterol homeostasis in RTT.

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.

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 Effects of recombinant human macrophage colony-stimulating factor on plasma cholesterol levels

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 750-755 ◽  
Author(s):  
JB Stoudemire ◽  
MB Garnick
Keyword(s):  
Nonhuman Primates ◽  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Human Macrophage ◽  
Cholesterol Levels ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Recombinant human macrophage colony-stimulating factor (rhM-CSF) is a hematopoietic growth factor that stimulates the growth, differentiation, proliferation, and activation of cells of the monocyte/macrophage lineage. rhM-CSF was administered to rabbits and nonhuman primates to evaluate effects on cholesterol homeostasis. Decreases in plasma cholesterol concentrations were observed during rhM- CSF administration. The observed mean (+/- SD) decreases over a range of doses in nonhuman primates receiving rhM-CSF by continuous intravenous infusion (CIVI) or intravenous bolus (IVB) injection were approximately 16% +/- 8% and 43% +/- 10%, respectively. Low-density lipoprotein (LDL) cholesterol levels decreased 55% +/- 9% from pretreatment baseline values in the animals receiving rhM-CSF by IVB. Normocholesterolemic New Zealand white rabbits receiving rhM-CSF over a range of doses by CIVI showed a decrease from baseline in total cholesterol of approximately 28% +/- 17%, with LDL cholesterol levels decreasing by approximately 72% +/- 33%, while high-density lipoprotein levels showed variable changes, including increased values. A decrease of 36% +/- 26% in total plasma cholesterol was observed in Watanabe Heritable Hyperlipidemic rabbits receiving rhM-CSF by CIVI for 7 days. This decrease was attributable almost entirely to decreases in LDL cholesterol, which fell approximately 34% +/- 24% from baseline. Although the mechanism of this cholesterol-lowering effect is unknown, these results strongly suggest that rhM-CSF may provide a novel treatment for hypercholesterolemia and may be useful in investigations into the mechanisms of cholesterol homeostasis and atherogenesis.

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