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      Effect of high carbohydrate diet on elongase and desaturase activity and accompanying gene expression in rat’s liver

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          Abstract

          Background

          Hepatic fatty acids (FAs) are modified through different metabolic pathways including elongation and desaturation. These processes are catalyzed by elongases and desaturases, respectively. Glucose, by transcription factors, regulates these processes. The aim of the study was to evaluate the influence of high carbohydrate diet (68%) on the expression of elongase (Elovl-2, Elovl-5, and Elovl-6) and desaturase (∆5D, ∆6D, Scd 1, Scd 2) genes and the activity of the enzymes. The changes in serum lipid profile (triglycerides (TG), total cholesterol (TC), HDL cholesterol) and glucose concentration were measured. Male Wistar rats were randomized into two study groups: animals fed with high carbohydrate diet ( n = 6; HiCHO) and a control group fed with a standard diet ( n = 6; ST). The expression of mRNA was determinate using reverse transcription PCR (RT-PCR). Hepatic FA composition was determined by gas chromatography, and FA ratios were used to estimate the activity of enzymes. Serum lipid profile and glucose concentration were measured using spectrophotometric methods.

          Results

          The mean values of transcript expression of all examined elongases and desaturases in liver HiCHO rats were higher as compared to ST. Higher expression did not always correspond to higher activity (as index). More monounsaturated FAs (MUFAs) were detected in the liver of HiCHO rats as compared to ST. Serum TG level was higher in the HiCHO than in ST.

          Conclusions

          These studies support the notion that the regulation of both Elovl and desaturase expression may play an important role in managing hepatic lipid composition in response to changes in dietary status.

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          Most cited references29

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          A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver.

          Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity in vitro precisely correlates with promoter activity in vivo. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.
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            Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes.

            Roles of sterol regulatory element-binding proteins (SREBPs) have been established as lipid synthetic transcription factors especially for cholesterol and fatty acid synthesis. SREBPs have unique characteristics. Firstly, they are membrane-bound proteins and the N-terminal active portions enter nucleus to activate their target genes after proteolytic cleavage, which requires sterol-sensing molecule, SREBP-activating protein (SCAP) and is crucial for sterol-regulation. Secondly, they bind and activate sterol-regulatory (SREs) containing promoters as well as some E-boxes, which makes SREBPs eligible to regulate a wide range of lipid genes. Finally, three isoforms, SREBP-1a-1c, and have different roles in lipid synthesis. In vivo studies using transgenic and knockout mice suggest that SREBP-1 seems to be involved in energy metabolism including fatty acid and glucose/insulin metabolism, whereas SREBP-2 is specific to cholesterol synthesis. Future studies will be focused on understanding molecular mechanisms sensing cellular sterol and energy states where SREBPs are deeply involved.
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              The Rapid Preparation of Fatty Acid Esters for Gas Chromatographic Analysis

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                Author and article information

                Contributors
                jagoda.drag@gmail.com
                Journal
                Genes Nutr
                Genes Nutr
                Genes & Nutrition
                BioMed Central (London )
                1555-8932
                1865-3499
                25 January 2017
                25 January 2017
                2017
                : 12
                : 2
                Affiliations
                [1 ]ISNI 0000 0001 2162 9631, GRID grid.5522.0, Department of Analytical Biochemistry, Faculty of Pharmacy, , Jagiellonian University Medical College, ; Krakow, Poland
                [2 ]GRID grid.445217.1, Faculty of Health and Medical Sciences, , Andrzej Frycz Modrzewski Krakow University, ; Krakow, Poland
                [3 ]ISNI 0000 0001 2162 9631, GRID grid.5522.0, Department of Diagnostics, Chair of Clinical Biochemistry, , Jagiellonian University Medical College, ; Krakow, Poland
                [4 ]GRID grid.445217.1, , Andrzej Frycz Modrzewski Krakow University, ; 1 G. Herlinga-Grudzińskiego St., 30-705 Krakow, Poland
                Article
                551
                10.1186/s12263-017-0551-9
                5264288
                f6e0a709-b427-4128-9c6f-61c62e4c38ed
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 August 2016
                : 14 October 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Nutrition & Dietetics
                elongases,desaturases,fatty acids,high carbohydrate diet
                Nutrition & Dietetics
                elongases, desaturases, fatty acids, high carbohydrate diet

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