Effects of chronic hyperinsulinaemia on hepatic enzymes involved in lipogenesis and carbohydrate metabolism in the young rat.
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ABSTRACT:
SUBMITTER: McCormick KL
PROVIDER: S-EPMC1185699 | biostudies-other | 1978 May
REPOSITORIES: biostudies-other
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Project description:Dr. Eric Vivier's lab would like to tackle the enzymes involved in PEN5 carbohydrate metabolism. We have generated these cell lines by repeated cell sorting and cell cloning of the parental HSB-2 T cell line and the parental JY B cell line. H+ are PEN5+ HSB-2 cells, H- are PEN5- HSB-2 cells; JY+ are PEN5+ HSB-2 cells, JY- are PEN5- HSB-2 cells. We have originally described a cell surface molecule called PEN5, as a sulfated lactosamine, that is selectively expressed on a mature subset of human NK cells (Vivier, J. Exp. Med. 1993). Later, we have shown that the PEN5 carbohydrate decorates PSGL-1, confering L-selectin binding properties (André et al. PNAS, 2000). We have recently performed a Glycan Array Screening via Core H (Glycomics 917). These studies indeed reveal a very nice binding of the anti-PEN5 mAb to a subset of sulfated lactosamines. We would like to tackle the enzymes involved in PEN5 carbohydrate metabolism. We thus requesting a Gene microarray analysis performed using RNA extracted from PEN5+ and PEN5- NK cells, as well from the H+, H-, JY+ and JY- stable cell lines. We have generated these cell lines by repeated cell sorting and cell cloning of the parental HSB-2 T cell line and the parental JY B cell line. H+ are PEN5+ HSB-2 cells, H- are PEN5- HSB-2 cells; JY+ are PEN5+ HSB-2 cells, JY- are PEN5- HSB-2 cells. RNA preparations from variants of the HSB-2 (human T leukemia) and JY (human B lymphoma) cell lines, which were express or not PEN5 were sent to Microarray Core (E). These stable variants are referred to as H+ (HSB-2 cells expressing PEN5), H- (HSB-2 cells NOT expressing PEN5), JY+ (JY cells expressing PEN5), and JY- (JY cells NOT expressing PEN5). Samples were prepared at 3 different time points. The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays. Data was sent to Dr. Eric Vivier for analysis.
2011-06-14 | E-GEOD-29931 | biostudies-arrayexpress
Project description:Dr. Eric Vivier's lab would like to tackle the enzymes involved in PEN5 carbohydrate metabolism. We have generated these cell lines by repeated cell sorting and cell cloning of the parental HSB-2 T cell line and the parental JY B cell line. H+ are PEN5+ HSB-2 cells, H- are PEN5- HSB-2 cells; JY+ are PEN5+ HSB-2 cells, JY- are PEN5- HSB-2 cells.
2011-06-14 | GSE29931 | GEO
Project description:Glycans comprise ubiquitous and essential biopolymers, which usually occur as highly diverse mixtures. The myriad different structures are generated by a limited number of carbohydrate-active enzymes (CAZymes), which are unusual in that they catalyze multiple reactions by being relatively unspecific with respect to substrate size. Existing experimental and theoretical descriptions of CAZyme-mediated reaction systems neither comprehensively explain observed action patterns nor suggest biological functions of polydisperse pools in metabolism. Here, we overcome these limitations with a novel theoretical description of this important class of biological systems in which the mixing entropy of polydisperse pools emerges as an important system variable. In vitro assays of three CAZymes essential for central carbon metabolism confirm the power of our approach to predict equilibrium distributions and non-equilibrium dynamics. A computational study of the turnover of the soluble heteroglycan pool exemplifies how entropy-driven reactions establish a metabolic buffer in vivo that attenuates fluctuations in carbohydrate availability. We argue that this interplay between energy- and entropy-driven processes represents an important regulatory design principle of metabolic systems.
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Project description:BACKGROUND:Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. RESULTS:We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis. CONCLUSION:A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat.
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Project description:Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment.
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Project description:1. Lipogenesis in sheep liver and adipose tissue was investigated by incorporation studies in vitro with radioactive glucose and acetate and by assays of key enzymes. 2. Carbohydrate availability to sheep was increased by feeding on a diet containing 70% soluble carbohydrate, by infusing glucose into the abomasum or by direct intravenous infusion of glucose. 3. Under these conditions lipogenesis from glucose and acetate was increased from very low values in lìver and adipose tissue, especially in those animals where rumen fermentation was by-passed by glucose infusion. 4. Large increases in the activities of ATP citrate lyase (EC 4.1.3.8) and NADP-malate dehydrogenase (EC 1.1.1.40) occurred in both tissues when lipogenesis was increased. 5. No adaptations were found in the activities of pyruvate carboxylase (EC 6.4.1.1) in adipose tissue, glucokinase (EC 2.7.1.2) in liver or 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in liver. It is proposed that the absence of these enzymes is not related to glucose availability. 6. The effect of glucose on liver lipogenesis was to increase conversion of acetate into lipid. 7. This effect also occurred in adipose tissue, but in this tissue glucose also became a quantitatively important precursor of triglyceride fatty acid.
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Project description:The effects of beverage alcohol (ethanol) on the body are determined largely by the rate at which it and its main breakdown product, acetaldehyde, are metabolized after consumption. The main metabolic pathway for ethanol involves the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Seven different ADHs and three different ALDHs that metabolize ethanol have been identified. The genes encoding these enzymes exist in different variants (i.e., alleles), many of which differ by a single DNA building block (i.e., single nucleotide polymorphisms [SNPs]). Some of these SNPs result in enzymes with altered kinetic properties. For example, certain ADH1B and ADH1C variants that are commonly found in East Asian populations lead to more rapid ethanol breakdown and acetaldehyde accumulation in the body. Because acetaldehyde has harmful effects on the body, people carrying these alleles are less likely to drink and have a lower risk of alcohol dependence. Likewise, an ALDH2 variant with reduced activity results in acetaldehyde buildup and also has a protective effect against alcoholism. In addition to affecting drinking behaviors and risk for alcoholism, ADH and ALDH alleles impact the risk for esophageal cancer.
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Project description:The freshwater clam (Corbicula spp.) is a popular edible bivalve and has been used as a folk remedy for liver disease in Asia. As a Chinese traditional medicine, it is said that freshwater clam ameliorates alcoholic intoxication and cholestasis. In this study, to estimate the practical benefit of freshwater clam extract (FCE), we compared the effects of FCE and soy protein isolate (SPI) on triglyceride and cholesterol metabolism in rats. FCE and SPI lowered serum cholesterol, and FCE tended to reduce serum triglycerides. FCE enhanced fecal sterol excretion and hepatic mRNA levels of CYP7A1 and ABCG5 more substantially than SPI; however, both diets reduced hepatic cholesterol. Both of the diets similarly suppressed liver lipids improved ?9-desaturated fatty acid profile, and FCE was associated with a reduction in FAS and SCD1 mRNA levels. Hepatic transcriptome analysis revealed that inhibition of lipogenesis-related gene expression may contribute to downregulation of hepatic triglycerides by FCE. FCE would have better potential benefits for preventing metabolic disorders, through greater improvement of metabolism of triglycerides and cholesterol, likely through a mechanism similar to SPI.
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