Raphani Semen (Raphanus sativus L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis.
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ABSTRACT:
SUBMITTER: Park WY
PROVIDER: S-EPMC8705906 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Raphanus sativus is an important Brassicaceae plant and also an edible vegetable with great economic value. However, currently there is not enough transcriptome information of R. sativus tissues, which impedes further functional genomics research on R. sativus. In this study, RNA-seq technology was employed to characterize the transcriptome of leaf tissues. Approximately 70 million clean pair-end reads were obtained and used for de novo assembly by Trinity program, which generated 68,086 unigenes with an average length of 576 bp. All the unigenes were annotated against GO and KEGG databases. In the meanwhile, we merged leaf sequencing data with existing root sequencing data and obtained better de novo assembly of R. sativus using Oases program. Accordingly, potential simple sequence repeats (SSRs), transcription factors (TFs) and enzyme codes were identified in R. sativus. Additionally, we detected a total of 3563 significantly differentially expressed genes (DEGs, P = 0.05) and tissue-specific biological processes between leaf and root tissues. Furthermore, a TFs-based regulation network was constructed using Cytoscape software. Taken together, these results not only provide a comprehensive genomic resource of R. sativus but also shed light on functional genomic and proteomic research on R. sativus in the future.
| S-EPMC4428447 | biostudies-literature
Project description:Aims/hypothesisNon-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development.MethodsTcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2f/f). Alb-Cre;Tcf7l2f/f and their wild-type (Tcf7l2f/f) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology.ResultsAlb-Cre;Tcf7l2f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions.Conclusions/interpretationIn mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL.Data availabilityRNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449 ).
| S-EPMC10036287 | biostudies-literature
Project description:BACKGROUND: Radish (Raphanus sativus L.), is an important root vegetable crop worldwide. Glucosinolates in the fleshy taproot significantly affect the flavor and nutritional quality of radish. However, little is known about the molecular mechanisms underlying glucosinolate metabolism in radish taproots. The limited availability of radish genomic information has greatly hindered functional genomic analysis and molecular breeding in radish. RESULTS: In this study, a high-throughput, large-scale RNA sequencing technology was employed to characterize the de novo transcriptome of radish roots at different stages of development. Approximately 66.11 million paired-end reads representing 73,084 unigenes with a N50 length of 1,095 bp, and a total length of 55.73 Mb were obtained. Comparison with the publicly available protein database indicates that a total of 67,305 (about 92.09% of the assembled unigenes) unigenes exhibit similarity (e -value???1.0e??) to known proteins. The functional annotation and classification including Gene Ontology (GO), Clusters of Orthologous Group (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the main activated genes in radish taproots are predominantly involved in basic physiological and metabolic processes, biosynthesis of secondary metabolite pathways, signal transduction mechanisms and other cellular components and molecular function related terms. The majority of the genes encoding enzymes involved in glucosinolate (GS) metabolism and regulation pathways were identified in the unigene dataset by targeted searches of their annotations. A number of candidate radish genes in the glucosinolate metabolism related pathways were also discovered, from which, eight genes were validated by T-A cloning and sequencing while four were validated by quantitative RT-PCR expression profiling. CONCLUSIONS: The ensuing transcriptome dataset provides a comprehensive sequence resource for molecular genetics research in radish. It will serve as an important public information platform to further understanding of the molecular mechanisms involved in biosynthesis and metabolism of the related nutritional and flavor components during taproot formation in radish.
| S-EPMC4046679 | biostudies-literature
Project description:BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.
| S-EPMC7269561 | biostudies-literature
Project description:Radish (Raphanus sativus L.) is an important annual or biennial root vegetable crop. The fleshy taproot comprises the main edible portion of the plant with high nutrition and medical value. Molecular biology study of radish begun rather later, and lacks sufficient transcriptomic and genomic data in pubic databases for understanding of the molecular mechanism during the radish taproot formation. To develop a comprehensive overview of the 'NAU-YH' root transcriptome, a cDNA library, prepared from three equally mixed RNA of taproots at different developmental stages including pre-cortex splitting stage, cortex splitting stage, and expanding stage was sequenced using high-throughput Illumina RNA sequencing. From approximately 51 million clean reads, a total of 70,168 unigenes with a total length of 50.28 Mb, an average length of 717 bp and a N50 of 994 bp were obtained. In total, 63,991 (about 91.20% of the assembled unigenes) unigenes were successfully annotated in five public databases including NR, GO, COG, KEGG, and Nt. GO analysis revealed that the majority of these unigenes were predominately involved in basic physiological and metabolic processes, catalytic, binding, and cellular process. In addition, a total of 103 unigenes encoding eight enzymes involved in the sucrose metabolism related pathways were also identified by KEGG pathway analysis. Sucrose synthase (29 unigenes), invertase (17 unigenes), sucrose-phosphate synthase (16 unigenes), fructokinase (17 unigenes), and hexokinase (11 unigenes) ranked top five in these eight key enzymes. From which, two genes (RsSuSy1, RsSPS1) were validated by T-A cloning and sequenced, while the expression of six unigenes were profiled with RT-qPCR analysis. These results would be served as an important public reference platform to identify the related key genes during taproot thickening and facilitate the dissection of molecular mechanisms underlying taproot formation in radish.
| S-EPMC4868836 | biostudies-literature
Project description:Background/objectivesFasting dyslipidemia is commonly observed in insulin resistant states and mechanistically linked to hepatic overproduction of very low density lipoprotein (VLDL). Recently, the incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in ameliorating dyslipidemia associated with insulin resistance and reducing hepatic lipid stores. Given that hepatic VLDL production is a key determinant of circulating lipid levels, we investigated the role of both peripheral and central GLP-1 receptor (GLP-1R) agonism in regulation of VLDL production.MethodsThe fructose-fed Syrian golden hamster was employed as a model of diet-induced insulin resistance and VLDL overproduction. Hamsters were treated with the GLP-1R agonist exendin-4 by intraperitoneal (ip) injection for peripheral studies or by intracerebroventricular (ICV) administration into the 3rd ventricle for central studies. Peripheral studies were repeated in vagotomised hamsters.ResultsShort term (7-10 day) peripheral exendin-4 enhanced satiety and also prevented fructose-induced fasting dyslipidemia and hyperinsulinemia. These changes were accompanied by decreased fasting plasma glucose levels, reduced hepatic lipid content and decreased levels of VLDL-TG and -apoB100 in plasma. The observed changes in fasting dyslipidemia could be partially explained by reduced respiratory exchange ratio (RER) thereby indicating a switch in energy utilization from carbohydrate to lipid. Additionally, exendin-4 reduced mRNA markers associated with hepatic de novo lipogenesis and inflammation. Despite these observations, GLP-1R activity could not be detected in primary hamster hepatocytes, thus leading to the investigation of a potential brain-liver axis functioning to regulate lipid metabolism. Short term (4 day) central administration of exendin-4 decreased body weight and food consumption and further prevented fructose-induced hypertriglyceridemia. Additionally, the peripheral lipid-lowering effects of exendin-4 were negated in vagotomised hamsters implicating the involvement of parasympathetic signaling.ConclusionExendin-4 prevents fructose-induced dyslipidemia and hepatic VLDL overproduction in insulin resistance through an indirect mechanism involving altered energy utilization, decreased hepatic lipid synthesis and also requires an intact parasympathetic signaling pathway.
| S-EPMC4264039 | biostudies-literature
Project description:In non-alcoholic fatty liver disease (NAFLD) caused by ectopic lipid accumulation, lipotoxicity is a crucial molecular risk factor. Mechanisms to eliminate lipid overflow can prevent the liver from functional complications. This may involve increased secretion of lipids or metabolic adaptation to ß-oxidation in lipid-degrading organelles such as mitochondria and peroxisomes. In addition to dietary factors, increased plasma fatty acid levels may be due to increased triglyceride synthesis, lipolysis, as well as de novo lipid synthesis (DNL) in the liver. In the present study, we investigated the impact of fatty liver caused by elevated DNL, in a transgenic mouse model with liver-specific overexpression of human sterol regulatory element-binding protein-1c (alb-SREBP-1c), on hepatic gene expression, on plasma lipids and especially on the proteome of peroxisomes by omics analyses, and we interpreted the results with knowledge-based analyses. In summary, the increased hepatic DNL is accompanied by marginal gene expression changes but massive changes in peroxisomal proteome. Furthermore, plasma phosphatidylcholine (PC) as well as lysoPC species were altered. Based on these observations, it can be speculated that the plasticity of organelles and their functionality may be directly affected by lipid overflow.
| S-EPMC6823594 | biostudies-literature
Project description:BackgroundObservational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however, it remains to be elucidated whether these markers accurately reflect hepatic DNL.ObjectivesWe investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet.MethodsFasting hepatic DNL was assessed using 2H2O (deuterated water) in 149 nondiabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate. FA markers of blood lipid fractions were determined by gas chromatography.ResultsNeither the lipogenic index (16:0/18:2n-6) nor the SCD index (16:1n-7/16:0) in VLDL-TG was associated with isotopically assessed DNL (r = 0.13, P = 0.1 and r = -0.08, P = 0.35, respectively). The relative abundances (mol%) of 14:0, 16:0, and 18:0 in VLDL-TG were weakly (r ≤ 0.35) associated with DNL, whereas the abundances of 16:1n-7, 18:1n-7, and 18:1n-9 were not associated. When the cohort was split by median DNL, only the abundances of 14:0 and 18:0 in VLDL-TG could discriminate between subjects having high (11.5%) and low (3.8%) fasting hepatic DNL. Based on a subgroup, FA markers in total plasma TG, plasma cholesteryl esters, plasma phospholipids, and red blood cell phospholipids were generally not associated with DNL.ConclusionsThe usefulness of circulating FAs as markers of hepatic DNL in healthy individuals consuming their habitual diet is limited due to their inability to discriminate clearly between individuals with low and high fasting hepatic DNL.
| S-EPMC6367991 | biostudies-literature
Project description:BACKGROUND:The HongXin radish (Raphanus sativus L.), which contains the natural red pigment (red radish pigment), is grown in the Fuling district of Chongqing City. However, the molecular mechanisms underlying anthocyanin synthesis for the formation of natural red pigment in the fleshy roots of HongXin radish are not well studied. RESULTS:De novo transcriptome of HX-1 radish, as well as that of the advanced inbred lines HX-2 and HX-3 were characterized using next generation sequencing (NGS) technology. In total, approximately 66.22 million paired-end reads comprising 34, 927 unigenes (N50?=?1, 621?bp) were obtained. Based on sequence similarity search with known proteins, total of 30, 127 (about 86.26%) unigenes were identified. Additionally, functional annotation and classification of these unigenes indicated that most of the unigenes were predominantly enriched in the metabolic process-related terms, especially for the biosynthetic pathways of secondary metabolites. Moreover, majority of the anthocyanin biosynthesis-related genes (ABRGs) involved in the regulation of anthocyanin biosynthesis were identified by targeted search for their annotation. Subsequently, the expression of 15 putative ABRGs involved in the anthocyanin synthesis-related pathways were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Of those, RsPAL2, RsCHS-B2, RsDFR1, RsDFR2, RsFLS, RsMT3 and RsUFGT73B2-like were identified significantly associated with anthocyanin biosynthesis. Especially for RsDFR1, RsDFR2 and RsFLS, of those, RsDFR1 and RsDFR2 were highest enriched in the HX-3 and WG-3, but RsFLS were down-regulated in HX-3 and WG-3. We proposed that the transcripts of RsDFR1, RsDFR2 and RsFLS might be act as key regulators in anthocyanin biosynthesis pathway. CONCLUSIONS:The assembled radish transcript sequences were analysed to identify the key ABRGs involved in the regulation of anthocyanin biosynthesis. Additionally, the expression patterns of candidate ABRGs involved in the anthocyanin biosynthetic pathway were validated by qRT-PCR. We proposed that the transcripts of RsDFR1, RsDFR2 and RsFLS might be acted as key regulators in anthocyanin biosynthesis pathway. This study will enhance our understanding of the biosynthesis and metabolism of anthocyanin in radish.
| S-EPMC6813128 | biostudies-literature
Project description:Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.
| S-EPMC7170906 | biostudies-literature