scholarly journals Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Chikako Sugiura ◽  
Shiho Nishimatsu ◽  
Tatsuya Moriyama ◽  
Sayaka Ozasa ◽  
Teruo Kawada ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Epigallocatechin Gallate ◽  
Acid Synthesis ◽  
Control Group ◽  
Mrna Levels ◽  
Fat Accumulation ◽  
Treatment Groups ◽  
Fas Mrna ◽  
Carnitine Palmitoyltransferase Ii

To elucidate the inhibiting mechanisms of fat accumulation by catechins, caffeine, and epigallocatechin gallate (EGCG), ICR mice were fed diets containing either 0.3% catechins or 0.1% EGCG and/or 0.05% caffeine for 4 weeks. After the feeding, intraperitoneal adipose tissues weights were significantly lower in the caffeine, catechins + caffeine, and EGCG + caffeine groups compared to controls. Hepatic fatty acid synthase (FAS) activity in the catechins + caffeine group was significantly lower, and the activities of acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-II (CPT-II) were significantly higher, compared to the control group. However, these activities were not observed in the other groups. FAS mRNA expression levels in the catechins + caffeine group were significantly lower than in the control group. ACO and CPT-II mRNA levels were not different among all of the treatment groups. These findings indicate that the inhibitory effects of fat accumulation via a combination of catechins, EGCG, or caffeine were stronger collectively than by either catechins, EGCG, or caffeine alone. Moreover, it was demonstrated that the combination of catechins and caffeine induced inhibition of fat accumulation by suppression of fatty acid synthesis and upregulation of the enzymatic activities involved inβ-oxidation of fatty acid in the liver, but this result was not observed by combination of EGCG and caffeine.

scholarly journals Somatotropin-dependent decrease in fatty acid synthase mRNA abundance in 3T3-F442A adipocytes is the result of a decrease in both gene transcription and mRNA stability

1998 ◽  
Vol 331 (3) ◽  
pp. 815-820 ◽  
Author(s):  
Dezhong YIN ◽  
Steven D. CLARKE ◽  
Jana L. PETERS ◽  
Terry D. ETHERTON
Keyword(s):  
Fatty Acid ◽  
Mrna Stability ◽  
Fatty Acid Synthase ◽  
Insulin Treatment ◽  
Acid Synthesis ◽  
Mrna Abundance ◽  
Mrna Levels ◽  
Reporter Construct ◽  
Fas Mrna ◽  
Flanking Region

Somatotropin (ST) markedly decreases lipogenesis, fatty acid synthase (FAS) enzyme activity and mRNA abundance in pig adipocytes. The present study was conducted to determine whether the decrease in FAS mRNA in 3T3-F442A adipocytes was the result of a decrease in transcription of the FAS gene and/or a change in FAS mRNA stability. Insulin increased the abundance of FAS mRNA 2–13-fold and fatty acid synthesis 3–7-fold. Somatotropin decreased the stimulatory effect of insulin on the abundance of FAS mRNA and lipogenesis by 40–70% and 20–60% respectively. Subsequent run-on analyses demonstrated that the decrease observed in FAS mRNA in response to ST was associated with an 82% decrease in transcription; ST significantly shortened the half-life of FAS mRNA from 35 to 11 h. To corroborate the run-on analyses, cells were stably transfected with a pFAS–CAT5 (in which CAT stands for chloramphenicol acetyltransferase) reporter construct that contained 2195 bp of the 5´ flanking region of the rat FAS gene. Insulin treatment increased FAS–CAT activity 4.7-fold. When ST was added to the insulin-containing medium there was an approx. 60% reduction in FAS–CAT activity. In summary, our results indicate that ST decreases FAS mRNA levels and that this is the result of a marked decrease in both transcription of the FAS gene and stability of the FAS mRNA.

scholarly journals 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway

2008 ◽  
Vol 295 (6) ◽  
pp. E1369-E1379 ◽  
Author(s):  
Yongjie Ma ◽  
Leyuan Xu ◽  
Daniel Rodriguez-Agudo ◽  
Xiaobo Li ◽  
Douglas M. Heuman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Lipid Synthesis ◽  
Mrna Levels ◽  
Intracellular Lipids ◽  
Protein Levels ◽  
Regulatory Molecule ◽  
Fas Mrna

The oxysterol receptor LXR is a key transcriptional regulator of lipid metabolism. LXR increases expression of SREBP-1, which in turn regulates at least 32 genes involved in lipid synthesis and transport. We recently identified 25-hydroxycholesterol-3-sulfate (25HC3S) as an important regulatory molecule in the liver. We have now studied the effects of 25HC3S and its precursor, 25-hydroxycholesterol (25HC), on lipid metabolism as mediated by the LXR/SREBP-1 signaling in macrophages. Addition of 25HC3S to human THP-1-derived macrophages markedly decreased nuclear LXR protein levels. 25HC3S administration was followed by dose- and time-dependent decreases in SREBP-1 mature protein and mRNA levels. 25HC3S decreased the expression of SREBP-1-responsive genes, acetyl-CoA carboxylase-1, and fatty acid synthase (FAS) as well as HMGR and LDLR, which are key proteins involved in lipid metabolism. Subsequently, 25HC3S decreased intracellular lipids and increased cell proliferation. In contrast to 25HC3S, 25HC acted as an LXR ligand, increasing ABCA1, ABCG1, SREBP-1, and FAS mRNA levels. In the presence of 25HC3S, 25HC, and LXR agonist T0901317, stimulation of LXR targeting gene expression was repressed. We conclude that 25HC3S acts in macrophages as a cholesterol satiety signal, downregulating cholesterol and fatty acid synthetic pathways via inhibition of LXR/SREBP signaling. A possible role of oxysterol sulfation is proposed.

The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription

1996 ◽  
Vol 16 (2) ◽  
pp. 151-158 ◽  
Author(s):  
S S Donkin ◽  
A D McNall ◽  
B S Swencki ◽  
J L Peters ◽  
T D Etherton
Keyword(s):  
Growth Hormone ◽  
Fatty Acid ◽  
Gene Transcription ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Hormone Treatment ◽  
Mrna Abundance ◽  
Transcription Rate ◽  
Mrna Levels ◽  
Fas Mrna

ABSTRACT The present study was conducted to determine the chronic effects of porcine growth hormone administration on fatty acid synthase (FAS) mRNA abundance and gene transcription in growing rats. Growth hormone treatment increased growth rate approximately 27% (P<0·01). Porcine growth hormone decreased FAS mRNA levels by 55%. The reduction in FAS mRNA was due to a marked decrease in transcription of the FAS gene (decreased by 80%). In contrast, porcine growth hormone did not affect mRNA abundance or transcription rate of another insulin-regulated gene, phosphoenolpyruvate carboxykinase. In summary, our results have established that chronic treatment with growth hormone decreases FAS mRNA by decreasing the transcription rate of the gene. Furthermore, they suggest that the effects of growth hormone are specific and are not mediated by general changes in insulin-responsive gene expression in liver.

scholarly journals Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy

2021 ◽  
Author(s):  
Magali Humbert ◽  
Kristina Seiler ◽  
Severin Mosimann ◽  
Vreni Rentsch ◽  
Katyayani Sharma ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Fatty Acid ◽  
Myeloid Leukemia ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Acid Synthesis ◽  
Mrna Levels ◽  
Differentiation Therapy ◽  
Granulocytic Differentiation ◽  
Acute Myeloid

AbstractFatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty acid synthesis and is often highly expressed in cancer cells. We found that FASN mRNA levels were significantly higher in acute myeloid leukemia (AML) patients than in healthy granulocytes or CD34+ hematopoietic progenitors. Accordingly, FASN levels decreased during all-trans retinoic acid (ATRA)-mediated granulocytic differentiation of acute promyelocytic leukemia (APL) cells, partially via autophagic degradation. Furthermore, our data suggest that inhibition of FASN expression levels using RNAi or (-)-epigallocatechin-3-gallate (EGCG) accelerated the differentiation of APL cell lines and significantly re-sensitized ATRA refractory non-APL AML cells. FASN reduction promoted translocation of transcription factor EB (TFEB) to the nucleus, paralleled by activation of CLEAR network genes and lysosomal biogenesis. Together, our data demonstrate that inhibition of FASN expression in combination with ATRA treatment facilitates granulocytic differentiation of APL cells and may extend differentiation therapy to non-APL AML cells.

Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses

2005 ◽  
Vol 288 (1) ◽  
pp. R104-R111 ◽  
Author(s):  
Junlong Zhang ◽  
Rohan M. Lewis ◽  
Chunli Wang ◽  
Nicholas Hales ◽  
Christopher D. Byrne
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Plasma Cholesterol ◽  
Liver Lipid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Liver Cholesterol ◽  
Mrna Levels ◽  
Protein Levels

Maternal dietary Fe restriction reduced fasting plasma cholesterol and triglyceride (TG) concentrations in the fetuses, as well as decreased plasma TG levels in the adult offspring. To investigate how maternal Fe restriction was affecting fetal lipid metabolism, we investigated whether there were changes in liver lipid metabolism in the full-term fetuses. There was a ∼27% ( P < 0.05) increase in cholesterol but ∼29% reduction ( P = 0.01) in TG concentrations in the liver of the Fe-restricted fetuses. Hepatic mRNA levels of cholesterol 7α hydroxylase and liver X receptor-α (LXRα) were reduced by ∼50% ( P < 0.01) and ∼34% ( P < 0.01), respectively. As LXRα regulates expression of sterol response element binding protein-1c (SREBP-1c) expression, we measured SREBP-1c expression. There was an ∼43% ( P < 0.001) reduction in mRNA levels of SREBP-1c and its response genes, including acetyl-CoA carboxylase by ∼35% ( P = 0.01), fatty acid synthase by ∼18% ( P = 0.05), and diacylglycerol acyltransferase by ∼19% ( P = 0.03). Furthermore, protein levels of CD36 were reduced by ∼27% ( P = 0.02) in Fe-restricted fetuses. In conclusion, changes in liver cholesterol and TG concentrations in Fe-restricted fetuses may be coordinated through reduced expression of heme-containing cholesterol 7α hydroxylase and its regulator LXRα, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.

scholarly journals Astaxanthin lowers plasma TAG concentrations and increases hepatic antioxidant gene expression in diet-induced obesity mice

2014 ◽  
Vol 112 (11) ◽  
pp. 1797-1804 ◽  
Author(s):  
Yue Yang ◽  
Tho X. Pham ◽  
Casey J. Wegner ◽  
Bohkyung Kim ◽  
Chai Siah Ku ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Plasma Concentrations ◽  
Control Group ◽  
Related Factor ◽  
Mrna Levels ◽  
Alcoholic Fatty Liver ◽  
Antioxidant Genes ◽  
Endogenous Antioxidant

Non-alcoholic fatty liver disease (NAFLD) is significantly associated with hyperlipidaemia and oxidative stress. We have previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TAG concentrations in apoE knockout mice. To investigate whether ASTX supplementation can prevent the development of NAFLD in obesity, male C57BL/6J mice (n 8 per group) were fed a high-fat diet (35 %, w/w) supplemented with 0, 0·003, 0·01 or 0·03 % of ASTX (w/w) for 12 weeks. The 0·03 % ASTX-supplemented group, but not the other groups, exhibited a significant decrease in plasma TAG concentrations, suggesting that ASTX at a 0·03 % supplementation dosage exerts a hypotriacylglycerolaemic effect. Although there was an increase in the mRNA expression of fatty acid synthase and diglyceride acyltransferase 2, the mRNA levels of acyl-CoA oxidase 1, a critical enzyme in peroxisomal fatty acid β-oxidation, exhibited an increase in the 0·03 % ASTX-supplemented group. There was a decrease in plasma alanine transaminase (ALT) and aspartate transaminase (AST) concentrations in the 0·03 % ASTX-supplemented group. There was a significant increase in the hepatic mRNA expression of nuclear factor erythroid 2-related factor 2 and its downstream genes, which are critical for endogenous antioxidant mechanism, in the 0·03 % ASTX-supplemented group. Furthermore, there was a significant decrease in the mRNA abundance of IL-6 in the primary splenocytes isolated from the 0·03 % ASTX-supplemented group upon lipopolysaccharide (LPS) stimulation when compared with that in the splenocytes isolated from the control group. In conclusion, ASTX supplementation lowered the plasma concentrations of TAG, ALT and AST, increased the hepatic expression of endogenous antioxidant genes, and rendered splenocytes less sensitive to LPS stimulation. Therefore, ASTX may prevent obesity-associated metabolic disturbances and inflammation.

scholarly journals Gene expression of enzymes regulating ketogenesis and fatty acid metabolism in regenerating rat liver

1994 ◽  
Vol 299 (1) ◽  
pp. 65-69 ◽  
Author(s):  
G Asins ◽  
J L Rosa ◽  
D Serra ◽  
G Gil-Gómez ◽  
J Ayté ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Surgical Stress ◽  
Control Point ◽  
Diabetic Rats ◽  
Carnitine Palmitoyltransferase ◽  
Mrna Levels ◽  
Carnitine Palmitoyltransferase I ◽  
Cpt I ◽  
Carnitine Palmitoyltransferase Ii

Levels of mRNA for mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II), fatty acid synthase (FAS) and actin were analysed during liver regeneration. mRNA levels for mitochondrial HMG-CoA synthase decreased rapidly, reaching a minimum 12 h after partial hepatectomy and returning to normal at 24-36 h. In contrast, CPT I, CPT II and FAS mRNAs increased throughout the period examined. Expression of actin increased significantly during regeneration. Levels of mRNA for mitochondrial HMG-CoA synthase also decreased as a result of surgical stress, although the effect of hepatectomy was much greater. We determined the levels of mitochondrial HMG-CoA synthase using specific antibodies. The amount of protein rapidly decreased, although less markedly than the corresponding mRNA levels. These results show that the decrease described in ketogenesis in partially hepatectomized rats correlated with the decrease in the expression of mitochondrial HMG-CoA synthase, suggesting that this enzyme may also be a control point in ketogenesis in the regenerating liver, as it is in normal and diabetic rats.

scholarly journals Antcin K, a Triterpenoid Compound fromAntrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects via Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in Muscles

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Yueh-Hsiung Kuo ◽  
Cheng-Hsiu Lin ◽  
Chun-Ching Shih ◽  
Chang-Syun Yang
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Protein Kinase ◽  
Total Cholesterol ◽  
Fatty Acid Synthase ◽  
Glucose Transporter ◽  
Control Group ◽  
Mrna Levels ◽  
Glucose Transporter 4 ◽  
Amp Activated Protein Kinase

The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body ofAntrodia camphorata,in vitroand further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group. It was observed that AnK-treated mice significantly lowered blood glucose, triglyceride, total cholesterol, and leptin levels in AnK-treated groups. Of interest, AnK at 40 mg/kg/day dosage displayed both antihyperglycemic effect comparable to Metf (300 mg/kg/day) and antihypertriglyceridemic effect comparable to Feno (250 mg/kg/day). The combination of significantly increased skeletal muscular membrane expression levels of glucose transporter 4 (GLUT4) but decreased hepatic glucose-6-phosphatase (G6 Pase) mRNA levels by AnK thus contributed to a decrease in blood glucose levels. Furthermore, AnK enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) expressions in the muscle and liver. Moreover, AnK treatment exhibited inhibition of hepatic fatty acid synthase (FAS) but enhancement of fatty acid oxidation peroxisome proliferator-activated receptorα(PPARα) expression coincident with reduced sterol response element binding protein-1c (SREBP-1c) mRNA levels in the liver may contribute to decreased plasma triglycerides, hepatic steatosis, and total cholesterol levels. The present findings indicate that AnK displays an advantageous therapeutic potential for the management of type 2 diabetes and hyperlipidemia.

Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity

1996 ◽  
Vol 270 (1) ◽  
pp. E192-E196 ◽  
Author(s):  
B. H. Jones ◽  
J. H. Kim ◽  
M. B. Zemel ◽  
R. P. Woychik ◽  
E. J. Michaud ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Ectopic Expression ◽  
Acid Synthesis ◽  
Mrna Levels ◽  
Simultaneous Treatment ◽  
Agouti Protein ◽  
Agouti Gene

Mutations leading to ectopic expression of the murine agouti gene (a) result in progressive obesity. To further characterize this model, we analyzed adipose and hepatic mRNA levels for fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD), two key enzymes in de novo fatty acid synthesis and desaturation, respectively. FAS and SCD mRNA in both tissues of obese (Avy) mice were dramatically increased relative to lean (ala) controls. Excessive expression of these genes in this model could be due to direct effects of the agouti gene product; to test this possibility we treated 3T3-L1 adipocytes in vitro with recombinant agouti protein. Agouti treatment increased FAS and SCD mRNA levels by 1.5- and 4-fold, respectively. In addition, FAS activity and triglyceride content were 3-fold higher in agoutitreated 3T3-L1 cells relative to controls; these effects were attenuated by simultaneous treatment with a calcium channel blocker (nitrendipine). These data demonstrate that the agouti protein can directly increase lipogenesis in adipocytes and suggest that these effects are mediated through an intracellular calcium-dependent mechanism.

scholarly journals Antidiabetic and Antihyperlipidemic Effects of Sulphurenic Acid, a Triterpenoid Compound from Antrodia camphorata, in Streptozotocin-Induced Diabetic Mice

2019 ◽  
Vol 20 (19) ◽  
pp. 4897 ◽  
Author(s):  
Cheng-Hsiu Lin ◽  
Li-Wei Hsiao ◽  
Yueh-Hsiung Kuo ◽  
Chun-Ching Shih
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Protective Effect ◽  
Fatty Acid Synthase ◽  
Control Group ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Antrodia Camphorata ◽  
Expression Levels ◽  
Lower Blood

The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.

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