scholarly journals Zinc, vanadate and selenate inhibit the tri-iodothyronine-induced expression of fatty acid synthase and malic enzyme in chick-embryo hepatocytes in culture

1994 ◽  
Vol 303 (1) ◽  
pp. 213-216 ◽  
Author(s):  
Y Zhu ◽  
A G Goodridge ◽  
S R Stapleton
Keyword(s):  
Fatty Acid ◽  
Chick Embryo ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Insulin Signalling ◽  
Mrna Levels ◽  
Maximal Inhibition ◽  
Induced Expression ◽  
Expression Of Genes ◽  
Insulin Signalling Pathway

Insulin regulates the expression of genes involved in a variety of metabolic processes. In chick-embryo hepatocytes in culture, insulin amplifies the tri-iodothyronine (T3)-induced enzyme activity, and the level and rate of transcription of mRNA for both fatty acid synthase (FAS) and malic enzyme (ME). Insulin alone, however, has little or no effect on the expression of these genes. In chick-embryo hepatocytes, the mechanism by which insulin regulates the expression of these or other genes is not known. Several recent studies have compared the effects of zinc, vanadate and selenate on insulin-sensitive processes in an attempt to probe the mechanism of insulin action. Because zinc, vanadate and selenate mimic the effects of insulin on several processes, they have been termed insulin-mimetics. We have studied the effect of zinc, vanadate and selenate on the T3-induced expression of both FAS and ME. Like insulin, these agents had little or no effect on the basal activities for FAS and ME in chick-embryo hepatocytes in culture for 48 h. Unlike insulin, however, zinc, vanadate and selenate inhibited the T3-induced activities and mRNA levels of both FAS and ME. Maximal inhibition was achieved at concentrations of 50 microM zinc or vanadate, or 20 microM selenate. Zinc and vanadate also inhibited the T3-induced transcription of the FAS and ME genes. Although the mechanism of this inhibition is unknown, our results indicate that it is not mediated through inhibition of binding of T3 to its nuclear receptor nor through a general toxic effect. Thus zinc, vanadate and selenate are not insulin-mimetics under all conditions, and their effects on other insulin-sensitive processes may be fortuitous and unrelated to actions or components of the insulin signalling pathway.

scholarly journals Alterations of Fatty Acid Profile May Contribute to Dyslipidemia in Chronic Kidney Disease by Influencing Hepatocyte Metabolism

2019 ◽  
Vol 20 (10) ◽  
pp. 2470 ◽  
Author(s):  
Aleksandra Czumaj ◽  
Tomasz Śledziński ◽  
Juan-Jesus Carrero ◽  
Piotr Stepnowski ◽  
Malgorzata Sikorska-Wisniewska ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Synthase ◽  
Density Lipoprotein ◽  
Atherogenic Dyslipidemia ◽  
Mrna Levels ◽  
Fa Composition ◽  
Expression Of Genes ◽  
Ckd Stage

Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis (fatty acid synthase (FASN) increased 13.7 ± 3.5 times, stearoyl-CoA desaturase 1 (SCD1) increased 4.26 ± 0.36 times), and very low density lipoprotein (VLDL) formation (apolipoprotein B (ApoB) increased 7.35 ± 1.5 times, microsomal triacylglycerol transfer protein (MTTP) increased 2.74 ± 0.43 times). In conclusion, there were progressive alterations in serum FA composition of patients with CKD. These alterations may partly contribute to CKD hypertriglyceridemia by influencing hepatocyte expression of genes of lipid synthesis and release.

scholarly journals Manganese influences the expression of fatty acid synthase and malic enzyme in cultured primary chicken hepatocytes

2017 ◽  
Vol 118 (11) ◽  
pp. 881-888 ◽  
Author(s):  
Lin Lu ◽  
Meiling Wang ◽  
Xiudong Liao ◽  
Liyang Zhang ◽  
Xugang Luo
Keyword(s):  
Fatty Acid ◽  
Mrna Expression ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Cell Damage ◽  
Manganese Chloride ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Expression Levels ◽  
Mrna Expression Levels

AbstractTwo experiments were designed to investigate the effects of Mn source and concentration on the mRNA expression and enzymatic activities of fatty acid synthase (FAS) and malic enzyme (ME) in cultured primary broiler hepatocytes. In Expt 1, primary broiler hepatocytes were treated with 0 (control), 0·25, 0·50 or 0·75 mmol/l of Mn as inorganic manganese chloride (MnCl2.4H2O) for 24 and 48 h. In Expt 2, primary broiler hepatocytes were incubated with 0 (control), 0·25 or 0·50 mmol/l of Mn as either manganese chloride or Mn–amino acid chelate for 48 h. The mRNA levels and activities of FAS and ME in the hepatocytes were measured in Expts 1 and 2. The results in Expt 1 showed that only at 48 h mRNA expression levels of FAS and ME in the hepatocytes decreased linearly (P<0·001) and quadratically (P<0·02) as supplemental Mn concentrations increased. In Expt 2, compared with the control, Mn supplementation reduced (P<0·01) the activities of FAS, mRNA expression levels of FAS and ME in the hepatocytes, and the efflux of lactic dehydrogenase to the medium. The supplemental Mn at 0·5 mmol/l showed a lower (P<0·03) ME mRNA expression level compared with the Mn group at 0·25 mmol/l. However, Mn source and the interaction between Mn source and concentration had no impacts (P>0·33) on any of the measured cellular parameters. The results suggested that Mn might reduce cell damage and regulate FAS and ME expression at a transcriptional level in primary cultured broiler hepatocytes.

scholarly journals Regulation of lipogenic capacity in lactating rats

1982 ◽  
Vol 208 (3) ◽  
pp. 611-618 ◽  
Author(s):  
M R Grigor ◽  
A Geursen ◽  
M J Sneyd ◽  
S M Warren
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Specific Activity ◽  
Mammary Glands ◽  
Lipogenic Enzymes ◽  
Pregnancy And Lactation ◽  
Specific Activities

1. The rate of mammary-gland lipogenesis measured in vivo from 3H2O was suppressed after decreasing the milk demand by decreasing the number of pups from ten to two or three, as well as by giving diets containing lipid [Grigor & Warren (1980) Biochem. J. 188, 61-65]. 2. The specific activities of the lipogenic enzymes fatty acid synthase, glucose 6-phosphate dehydrogenase and ‘malic’ enzyme increased between 6- and 10-fold in the mammary gland and between 2- and 3-fold in the livers during the first 10 days of lactation. The increases in specific activity coupled with the doubling of liver mass which occurred during pregnancy and lactation resulted in considerable differences in total liver activities when compared with virgin animals. 3. Although consumption of a diet containing 20% peanut oil suppressed the activities of the three lipogenic enzymes in the livers, only the ‘malic’ enzyme was affected in the mammary glands. 4. In contrast, decreased milk demand did not affect the specific activities of any of the liver enzymes, whereas it resulted in suppression of all three lipogenic enzymes of the mammary glands. There was no effect on either the cytoplasmic malate dehydrogenase or the lactate dehydrogenase of the mammary gland. 5. In all the experiments performed, the activity of the fatty acid synthase correlated with the amount of material precipitated by the rabbit antibody raised against rat fatty acid synthase.

scholarly journals Glucose stimulates transcription of fatty acid synthase and malic enzyme in avian hepatocytes

1998 ◽  
Vol 274 (3) ◽  
pp. E493-E501 ◽  
Author(s):  
F. Bradley Hillgartner ◽  
Tina Charron
Keyword(s):  
Fatty Acid ◽  
High Fat Diet ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Primary Cultures ◽  
Pentose Phosphate ◽  
Mrna Abundance ◽  
Low Fat Diet ◽  
Low Carbohydrate

Transcription of fatty acid synthase (FAS) and malic enzyme (ME) in avian liver is low during starvation or feeding a low-carbohydrate, high-fat diet and high during feeding a high-carbohydrate, low-fat diet. The role of glucose in the nutritional control of FAS and ME was investigated by determining the effects of this metabolic fuel on expression of FAS and ME in primary cultures of chick embryo hepatocytes. In the presence of triiodothyronine, glucose (25 mM) stimulated an increase in the activity and mRNA abundance of FAS and ME. These effects required the phosphorylation of glucose to glucose 6-phosphate but not further metabolism downstream of the aldolase step of the glycolytic pathway. Xylitol mimicked the effects of glucose on FAS and ME expression, suggesting that an intermediate of the pentose phosphate pathway may be involved in mediating this response. The effects of glucose on the mRNA abundance of FAS and ME were accompanied by similar changes in transcription of FAS and ME. These data support the hypothesis that glucose plays a role in mediating the effects of nutritional manipulation on transcription of FAS and ME in liver.

scholarly journals Placental insufficiency contributes to fatty acid metabolism alterations in aged female mouse offspring

2018 ◽  
Vol 315 (6) ◽  
pp. R1107-R1114 ◽  
Author(s):  
Violeta Stojanovska ◽  
Neha Sharma ◽  
Dorieke J. Dijkstra ◽  
Sicco A. Scherjon ◽  
Andrea Jäger ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Later Life ◽  
Placental Insufficiency ◽  
Mrna Levels ◽  
Artery Ligation ◽  
Nutritional Deprivation ◽  
Stress Markers ◽  
Metabolic Dysregulation ◽  
Glucose And Lipid Homeostasis

Intrauterine growth restriction (IUGR) is an accepted risk factor for metabolic disorders in later life, including obesity and type 2 diabetes. The level of metabolic dysregulation can vary between subjects and is dependent on the severity and the type of IUGR insult. Classical IUGR animal models involve nutritional deprivation of the mother or uterine artery ligation. The latter aims to mimic a placental insufficiency, which is the most frequent cause of IUGR. In this study, we investigated whether IUGR attributable to placental insufficiency impacts the glucose and lipid homeostasis at advanced age. Placental insufficiency was achieved by deletion of the transcription factor AP-2y ( Tfap2c), which serves as one of the major trophoblast differentiation regulators. TdelT-IUGR mice were obtained by crossing mice with a floxed Tfap2c allele and mice with Cre recombinase under the control of the Tpbpa promoter. In advanced adulthood (9–12 mo), female and male IUGR mice are respectively 20% and 12% leaner compared with controls. At this age, IUGR mice have unaffected glucose clearance and lipid parameters (cholesterol, triglycerides, and phospholipids) in the liver. However, female IUGR mice have increased plasma free fatty acids (+87%) compared with controls. This is accompanied by increased mRNA levels of fatty acid synthase and endoplasmic reticulum stress markers in white adipose tissue. Taken together, our results suggest that IUGR by placental insufficiency may lead to higher lipogenesis in female mice in advanced adulthood, at least indicated by greater Fasn expression. This effect was sex specific for the aged IUGR females.

scholarly journals Ergosterol Peroxide from the Medicinal Mushroom Ganoderma lucidum Inhibits Differentiation and Lipid Accumulation of 3T3-L1 Adipocytes

2020 ◽  
Vol 21 (2) ◽  
pp. 460 ◽  
Author(s):  
Yong-Un Jeong ◽  
Young-Jin Park
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Medicinal Mushrooms ◽  
Ergosterol Peroxide

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.

Fatty-acid synthase activity and mRNA level in hypertrophic type II cells from silica-treated rats

1994 ◽  
Vol 267 (2) ◽  
pp. L128-L136
Author(s):  
J. Rami ◽  
W. Stenzel ◽  
S. M. Sasic ◽  
C. Puel-M'Rini ◽  
J. P. Besombes ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Mrna Level ◽  
Type Ii Cells ◽  
Mrna Levels ◽  
Type Ii ◽  
Maximum Increase

Silica instillation causes a massive increase in lung surfactant. Two populations of type II pneumocytes can be isolated from rats administered silica by intratracheal injection: type IIA cells similar to type II cells from normal rats and type IIB cells, which are larger and contain elevated levels of surfactant protein A and phospholipid. Activities of choline-phosphate cytidylyltransferase, a rate-regulatory enzyme in phosphatidylcholine biosynthesis, and fatty-acid synthase (FAS) are increased in type IIB cells isolated from rats 14 days after silica injection. In the present study, we examined the increase in FAS and cytidylyltransferase activities in type IIB cells as a function of time after silica administration. FAS activity increased rapidly, was approximately threefold elevated 1 day after silica administration and has reached close to the maximum increase by 3 days. Cytidylyltransferase activity was not increased on day 1, was significantly increased on day 3 but was not maximally increased until day 7. Inhibition of de novo fatty-acid biosynthesis, by in vivo injection of hydroxycitric acid and inclusion of agaric acid in the type II cell culture medium, abolished the increase in cytidylyltransferase activity on day 3 but not FAS and had no effect on activities of two other enzymes of phospholipid synthesis. FAS mRNA levels were not increased in type IIB cells isolated 1-14 days after silica injection. These data show that the increase in FAS activity in type IIB cells is an early response to silica, that it mediates the increase in cytidylyltransferase activity, and that it is not due to enhanced FAS gene expression.

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