β-carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice
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ABSTRACT:
PROVIDER: PRJNA663568 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR12643170.fastq.gz | Fastqsanger.gz | |||
| SRR12643171.fastq.gz | Fastqsanger.gz | |||
| SRR12643172.fastq.gz | Fastqsanger.gz | |||
| SRR12643173.fastq.gz | Fastqsanger.gz | |||
| SRR12643174.fastq.gz | Fastqsanger.gz |
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Project description:Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of cardiovascular diseases (CVDs), and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affect atherosclerosis progression in the atheroprone low-density lipoprotein receptor (LDLR) - deficient mice. In comparison to control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and plasma cholesterol levels (P = 0.0003). These changes were absent in Ldlr-/-/Bco1-/- mice, despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
2020-11-12 | GSE157972 | GEO
Project description:Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels. These changes were absent in Ldlr-/- /Bco1-/- mice despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
| S-EPMC7604725 | biostudies-literature
Project description:The High-β-Carotene (HBC) mutant identified from EMS mutagenized population of cultivar Arka Vikas and the biochemical studies revealed that mutant fruits contain four times higher level of β-Carotene in comparison to Wild type (cv. Arka Vikas). We have developed whole genome microarray expression profiling as a discovery platform to identify differentially expressed genes in fruits containing High-β-Carotene mutant in comparison to Wild type (cv. Arka Vikas). Tomato fruit tissue samples from different stages of fruit ripening like Mature green, Breaker, Turning and Ripening stages of High-β-Carotene (HBC) mutant and Wild type (cv. Arka VIkas) were used for microarray gene expression analysis. Carotenoid pathway analysis of both mutant and wild type reveals that the high expression of chromoplast specific lycopene- β-cyclase gene in the HBC mutant, which is involved in the conversion of lycopene to β-carotene, but in wild type the expression of this gene, was low. Four genes (PSY, PDS, CRTISO, CYCB) of the carotenoid pathway was quantified in the same RNA samples by real-time PCR, confirming that the variation of the gene expression in HBC mutant.
2017-12-01 | GSE90964 | GEO
Project description:Soybeans (Glycine max) were genetically modified using a gene gun to produce beta-carotene, which is not normally found in the species. beta-carotene is produced in the chloroplast in which it competes with chlorophyl for production. A proteomics analysis was performed to determine the effects of the transgene on seed protein content.
2016-07-19 | PXD000709 | Pride
Project description:Cell culture studies indicate that beta-carotene-(BC)-derived apocarotenoid signaling molecules influence the activities of nuclear receptors that regulate many aspects of adipocyte physiology. Here, we analyzed the roles of the two BC metabolizing enzymes, BCMO1 and BCDO2, for this process in mouse models. Wild-type mice converted BC into retinoids and showed reduced body adiposity (by 28%), leptinemia and adipocyte size. Genome wide microarray analysis revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor gamma (PPARgamma) target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. This effect of BC was absent in Bcmo1-/- mice that showed increased BCDO2 expression and gamma-10gamma-apocarotenoid production. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARgamma activity. The goal of the study was to analyze the putative differential effects of BC accumulation on Bcmo1 ko mice, and BC metabolites in wt mice. Inguinal adipose tissue gene expression profile comparing adult male and female mice under control diet and beta-carotene (BC) supplemented diet during 14 weeks. 47 mice in total. 23 wild-type (11 male/12 female) and 24 bcmo1 (12 male/12 female) mice, fed on vitamin A diet (1500 IU vit A/kg diet) or vitamin A diet supplemented with BC (1500 IU vit A/kg diet +150 mg BC/kg diet) during 14 weeks.
2011-06-01 | E-GEOD-27271 | biostudies-arrayexpress
Project description:ObjectiveThe β-carotene oxygenase 1 (BCO1) is the enzyme responsible for the cleavage of β-carotene to retinal, the first intermediate in vitamin A formation. Preclinical studies suggest that BCO1 expression is required for dietary β-carotene to affect lipid metabolism. The goal of this study was to generate a gene therapy strategy that over-expresses BCO1 in the adipose tissue and utilizes the β-carotene stored in adipocytes to produce vitamin A and reduce obesity.MethodsWe generated a novel adipose-tissue-specific, adeno-associated vector to over-express BCO1 (AT-AAV-BCO1) in murine adipocytes. We tested this vector using a unique model to achieve β-carotene accumulation in the adipose tissue, in which Bco1-/- mice were fed β-carotene. An AT-AAV over-expressing green fluorescent protein was utilized as control. We evaluated the adequate delivery route and optimized cellular and organ specificity, dosage, and exposure of our vectors. We also employed morphometric analyses to evaluate the effect of BCO1 expression in adiposity, as well as HPLC and mass spectrometry to quantify β-carotene and retinoids in tissues, including retinoic acid.ResultsAT-AAV-BCO1 infusions in the adipose tissue of the mice resulted in the production of retinoic acid, a vitamin A metabolite with strong effects on gene regulation. AT-AAV-BCO1 treatment also reduced adipose tissue size and adipocyte area by 35% and 30%, respectively. These effects were sex-specific, highlighting the complexity of vitamin A metabolism in mammals.ConclusionsThe over-expression of BCO1 through delivery of an AT-AAV-BCO1 leads to the conversion of β-carotene to vitamin A in adipocytes, which subsequently results in reduction of adiposity. These studies highlight for the first time the potential of adipose tissue β-carotene as a target for BCO1 over-expression in the reduction of obesity.
| S-EPMC9707038 | biostudies-literature
Project description:Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in liver are largely unknown. We performed microarray gene expression analysis on liver tissue of BC supplemented beta-carotene 15,150-monooxygenase 1 knockout (Bcmo1-/-) mice, which are—like humans—able to accumulate BC. This was compared with litter mates being wild-type (Bcmo1+/+) mice, and we analysed both males and females, as we previously showed that in lung tissue we observed opposite gene regulation between males and females (Van Helden et al., CMLS 2011).
2017-09-26 | GSE98846 | GEO
Project description:Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,150-monooxygenase 1 knockout (Bcmo1-/-) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1-/- mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1-/- mice. Testosterone levels were higher after BC supplementation only in Bcmo1-/- mice, which had, unlike wild-type (Bcmo1+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.
2017-09-26 | GSE98845 | GEO
Project description:Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We show that microRNA-30c (miR-30c) interacts with the 3' untranslated region of MTP mRNA and induces its degradation, leading to reductions in MTP activity and in apolipoprotein B (APOB) secretion. miR-30c also reduces lipid synthesis independently of MTP. Hepatic overexpression of miR-30c reduced hyperlipidemia in Western diet-fed mice by decreasing lipid synthesis and the secretion of triglyceride-rich ApoB-containing lipoproteins and decreased atherosclerosis in Apoe(-/-) mice. Furthermore, inhibition of hepatic miR-30c by anti-miR-30c increased hyperlipidemia and atherosclerosis. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion, thereby regulating hepatic and plasma lipid concentrations. Raising miR-30c levels might be useful in treating hyperlipidemias and associated disorders.
| S-EPMC4121125 | biostudies-literature
Project description:The conversion of beta-carotene into retinal was studied in vitro with enzyme preparations from homogenates of hog intestinal mucosa. The hog mucosal enzyme was purified about 27-fold by precipitation with ammonium sulphate, chromatography on DEAE-Sephadex and gel filtration on Sephadex G-200. The reaction displayed a narrow optimum pH range (approx. 7.8-8.2). The enzyme was stimulated strongly by the addition of thiols, and was inhibited by thiol inhibitors and by the chelating agents alphaalpha'-bipyridyl and o-phenanthroline. The reaction required the addition of an appropriate detergent (or bile salt); maximal activity was obtained by addition of an appropriate combination of detergents and lipid (specifically Tween 40, sodium glycocholate and sphingomyelin). The reaction displayed Michaelis kinetics with K(m)1.3x10(-6)m and V(max.)1.1nmole of retinal formed/hr. (for 0.7mg. of enzyme protein). The properties of the hog enzyme are similar to those previously reported for a less purified rat enzyme preparation.
| S-EPMC1184953 | biostudies-other