22 results on '"Lipid liver level"'
Search Results
2. Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis
- Author
-
Hoeke, G., Wang, Y., Dam, A.D. van, Mol, M., Gart, E., Klop, H.G., Berg, S.M. van den, Pieterman, E.H., Princen, H.M.G., Groen, A.K., Rensen, P.C.N., Berbée, J.F.P., Boon, M.R., Hoeke, G., Wang, Y., Dam, A.D. van, Mol, M., Gart, E., Klop, H.G., Berg, S.M. van den, Pieterman, E.H., Princen, H.M.G., Groen, A.K., Rensen, P.C.N., Berbée, J.F.P., and Boon, M.R.
- Abstract
Background and aims Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. Methods APOE*3-Leiden.CETP mice were fed a Western-type diet and treated without or with the selective β3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results β3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by β3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by β3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to β3-AR agonism, also further reduced the atherosclerotic lesion size as compared to β3-AR agonism alone, without altering lesion severity and composition. Conclusions Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease.
- Published
- 2017
3. Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis
- Author
-
Elsbet H. Pieterman, Hans M.G. Princen, Andrea D. van Dam, Patrick C.N. Rensen, Jimmy F.P. Berbée, Eveline Gart, Yanan Wang, Isabel M. Mol, Albert K. Groen, Henk G. Klop, Geerte Hoeke, Susan M. van den Berg, Mariëtte R. Boon, ACS - Diabetes & metabolism, Experimental Vascular Medicine, Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Atherosclerosis & ischemic syndromes, Center for Liver, Digestive and Metabolic Diseases (CLDM), and Lifestyle Medicine (LM)
- Subjects
0301 basic medicine ,Mouse ,Mice, Knockout, ApoE ,Atorvastatin ,Biomedical Innovation ,030204 cardiovascular system & hematology ,Brown adipose tissue ,Animal tissue ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,High-density lipoprotein ,Adipose Tissue, Brown ,Life ,5 [2 [[2 (3 chlorophenyl) 2 hydroxyethyl]amino]propyl] 1,3 benzodioxole 2,2 dicarboxylic acid ,Hyperlipidemia ,Lipid and lipoprotein metabolism ,AGGRAVATES ATHEROSCLEROSIS ,Western diet ,Lipoprotein ,High density lipoprotein cholesterol ,Lipid liver level ,Lipid composition ,Proprotein convertase 9 ,Lipid transport ,Lipids ,Lipid oxidation ,Triacylglycerol blood level ,medicine.anatomical_structure ,ADIPOSE-TISSUE ,Cholesterol ,Cholesterol blood level ,Adipose Tissue ,Liver ,CARDIOVASCULAR-DISEASE ,PHOSPHOLIPID TRANSFER PROTEIN ,lipids (amino acids, peptides, and proteins) ,Female ,EELS - Earth, Environmental and Life Sciences ,Cardiology and Cardiovascular Medicine ,MHR - Metabolic Health Research ,Healthy Living ,medicine.drug ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Lipoproteins ,Hypercholesterolemia ,Drug potentiation ,Hyperlipidemias ,Biology ,Triacylglycerol ,APOLIPOPROTEIN-E ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Cholesterol metabolism ,Animal model ,cardiovascular diseases ,Animal experiment ,Triglycerides ,Lipoprotein metabolism ,Gene Expression Profiling ,nutritional and metabolic diseases ,Calorimetry, Indirect ,OXIDATIVE-METABOLISM ,medicine.disease ,Atherosclerosis ,Fatty acid ,Nonhuman ,Cholesterol Ester Transfer Proteins ,Drug effect ,030104 developmental biology ,Endocrinology ,Lipid metabolism ,chemistry ,Receptors, Adrenergic, beta-3 ,APOE-ASTERISK-3-LEIDEN.CETP MICE ,Energy expenditure ,Gene expression ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,HIGH-DENSITY-LIPOPROTEIN ,KNOCKOUT MICE ,Controlled study - Abstract
Background and aims: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. Methods: APOE*3-Leiden. CETP mice were fed a Western-type diet and treated without or with the selective beta 3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results: beta 3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by beta 3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by beta 3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to beta 3-AR agonism, also further reduced the atherosclerotic lesion size as compared to beta 3-AR agonism alone, without altering lesion severity and composition. Conclusions: Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease. (C) 2017 Elsevier B.V. All rights reserved
- Published
- 2017
4. Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis
- Subjects
Mouse ,Hypercholesterolemia ,Drug potentiation ,Biomedical Innovation ,Brown adipose tissue ,Triacylglycerol ,5 [2 [[2 (3 chlorophenyl) 2 hydroxyethyl]amino]propyl] 1 ,Animal tissue ,EELS - Earth ,Life ,Atorvastatin ,Cholesterol metabolism ,Lipid and lipoprotein metabolism ,Animal model ,cardiovascular diseases ,Animal experiment ,Western diet ,Lipoprotein ,Biology ,High density lipoprotein cholesterol ,Lipoprotein metabolism ,Lipid liver level ,Lipid composition ,nutritional and metabolic diseases ,Atherosclerosis ,Fatty acid ,Proprotein convertase 9 ,Lipid transport ,Nonhuman ,Environmental and Life Sciences ,Lipid oxidation ,Triacylglycerol blood level ,Drug effect ,2 dicarboxylic acid ,Cholesterol ,Cholesterol blood level ,Lipid metabolism ,3 benzodioxole 2 ,lipids (amino acids, peptides, and proteins) ,Energy expenditure ,Female ,Gene expression ,MHR - Metabolic Health Research ,Controlled study ,Healthy Living - Abstract
Background and aims Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. Methods APOE*3-Leiden.CETP mice were fed a Western-type diet and treated without or with the selective β3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results β3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by β3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by β3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to β3-AR agonism, also further reduced the atherosclerotic lesion size as compared to β3-AR agonism alone, without altering lesion severity and composition. Conclusions Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease.
- Published
- 2017
5. Serum adipokine profile and fatty acid composition of adipose tissues are affected by conjugated linoleic acid and saturated fat diets in obese Zucker rats
- Author
-
Rui Pinto, Susana V. Martins, Cristina M. Alfaia, Rui J.B. Bessa, José A. M. Prates, Matilde Castro, Paula A. Lopes, Susana P. Alves, P.O. Rodrigues, and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
- Subjects
Male ,obesity ,interleukin 1beta ,principal component analysis ,Conjugated linoleic acid ,Saturated fat ,cholesterol blood level ,Medicine (miscellaneous) ,Adipose tissue ,Palm Oil ,low density lipoprotein cholesterol ,chemistry.chemical_compound ,monounsaturated fatty acid ,Obese Zucker rats ,trans-10,cis-12-conjugated linoleic acid ,insulin resistance ,rat ,animal ,Linoleic Acids, Conjugated ,Epididymis ,chemistry.chemical_classification ,palm oil ,C reactive protein ,tumor necrosis factor alpha ,Nutrition and Dietetics ,saturated fatty acid ,retroperitoneal fat ,Fatty Acids ,article ,organ size ,Organ Size ,plasminogen activator inhibitor 1 ,polyunsaturated fatty acid ,Zucker rat ,Lipids ,adipose tissue ,fat intake ,Cholesterol ,vegetable oil ,Adipose Tissue ,Liver ,Saturated fatty acid ,Body Composition ,Polyunsaturated fatty acid ,lipid storage ,sheep ,medicine.medical_specialty ,Intra-Abdominal Fat ,Linoleic acid ,Saturated diets ,animal experiment ,adipocytokine ,interleukin 6 ,lipid liver level ,lipid composition ,Biology ,chemistry ,leptin ,Ovis ,animal tissue ,histology ,body weight ,liver weight ,SDG 3 - Good Health and Well-being ,Adipokines ,Dietary Fats, Unsaturated ,lipid ,blood ,atherogenic diet ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,medicine ,epididymis fat ,Animalia ,Animals ,Plant Oils ,controlled study ,Obesity ,intraabdominal fat ,nonhuman ,Sheep ,adiponectin ,Rattus ,trans 10,cis 12 conjugated linoleic acid ,animal model ,Fatty acid ,Dietary Fats ,Rats ,Rats, Zucker ,Endocrinology ,inflammation ,edible oil ,fatty acid ,metabolism - Abstract
Funding: The authors acknowledge Clinica Médica e Diagnóstico Dr Joaquim Chaves (Alge´s, Portugal) for the technical assistance regarding the serum lipids determination. The present study was supported by FCT POCTI/CVT/2002/44 750 and PTDC/CVT/2006/66 114 grants. S. V. M., P. A. L. and S. P. A. are the recipients of FCT individual fellowships SFRH/BD/2005/2256, SFRH/BPD/2005/23 931 and SFRH/ BD/2007/37 793, respectively. S. V. M., P. A. L. and C. M. A. performed the animal experiment, tissue sampling, laboratory work and prepared the manuscript. P. O. R. was responsible for Luminex xMAP analysis. S. P. A. and R. J. B. B. were responsible for fatty acid analysis. R. M. A. P. performed the biochemistry serum profile. S. V. M. and R. J. B. B. performed the statistical analysis. M. F. C. and J. A. M. P. were responsible for interpretation of the results, preparation of the manuscript and design of the study. Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2% cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1% of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-α and IL-1β. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that the trans-10, cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition. © 2009 The Authors. publishersversion published
- Published
- 2009
6. Rosuvastatin Reduces Plasma Lipids by Inhibiting VLDL Production and Enhancing Hepatobiliary Lipid Excretion in ApoE*3-Leiden Mice
- Author
-
Hans van der Boom, Karianne Solaas, Hans M.G. Princen, Vincent W. Bloks, Dianne J.M. Delsing, Folkert Kuipers, Wim van Duyvenvoorde, S.M. Post, Martine Groenendijk, Louis M. Havekes, Elly de Wit, Groningen University Institute for Drug Exploration (GUIDE), Center for Liver, Digestive and Metabolic Diseases (CLDM), and TNO Kwaliteit van Leven
- Subjects
Apolipoprotein E ,Very low-density lipoprotein ,Biomedical Research ,Cholesterol, VLDL ,cholesterol blood level ,Apolipoprotein E3 ,lipid blood level ,biliary excretion ,cholesterol diet ,DEFICIENT MICE ,hydroxymethylglutaryl coenzyme A reductase inhibitor ,Feces ,Mice ,chemistry.chemical_compound ,lipid metabolism ,Bile ,rat ,Rosuvastatin Calcium ,IN-VIVO ,Chromatography, High Pressure Liquid ,statistical significance ,BILE-ACID SYNTHESIS ,Sulfonamides ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,mevinolin ,enzyme activity ,very low density lipoprotein ,Sterols ,Cholesterol ,priority journal ,Liver ,HMG-CoA reductase ,Female ,lipids (amino acids, peptides, and proteins) ,Lovastatin ,Cardiology and Cardiovascular Medicine ,lipid diet ,medicine.drug ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Lipoproteins ,COA REDUCTASE INHIBITORS ,lipid liver level ,LIPOPROTEIN-LIPASE ,Mice, Transgenic ,lipid composition ,animal tissue ,CHOLESTEROL ACYLTRANSFERASE INHIBITOR ,Bile Acids and Salts ,Apolipoproteins E ,Internal medicine ,medicine ,Animals ,controlled study ,Rosuvastatin ,RNA, Messenger ,phospholipid ,mouse ,E-ASTERISK-3-LEIDEN TRANSGENIC MICE ,Triglycerides ,hepatobiliary system ,Apolipoproteins B ,Pharmacology ,nonhuman ,TRANSFER PROTEIN ,Triglyceride ,statin ,nutritional and metabolic diseases ,triacylglycerol blood level ,lipoproteins ,Fluorobenzenes ,Lipid metabolism ,APOLIPOPROTEIN-B SECRETION ,Pyrimidines ,Endocrinology ,chemistry ,cholesterol synthesis ,lipolysis ,gene expression ,biology.protein ,diacylglycerol acyltransferase ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,rosuvastatin - Abstract
The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (O [control], 0.00125%, 0.0025%, or 0.005% [w/w]) or 0.05% (w/w) lovastatin. The highest dose of rosuvastatin reduced plasma cholesterol and triglyceride levels by 39% and 42%, respectively, compared with the HFC control. Lovastatin had no effect on plasma cholesterol and triglyceride levels. In ApoE*3-Leiden mice on a chow diet, rosuvastatin (0.005% [w/w]) decreased plasma cholesterol levels by 35% without having an effect on triglyceride levels. On a chow diet, expression of genes involved in cholesterol biosynthesis and uptake in the liver was increased by rosuvastatin. Further mechanistic studies in HFC-fed mice showed that rosuvastatin treatment resulted in decreased hepatic VLDL-triglyceride and VLDL-apolipoprotein B production. VLDL lipid composition remained unchanged, indicating a reduction in the number of VLDL particles secreted. Lipolytic activity and expression of genes involved in cholesterol and triglyceride synthesis and β-oxidation of fatty acids in the liver were not affected by rosuvastatin treatment, and hepatic lipid content did not change. However, activity of hepatic diacylglycerol acyltransferase was significantly decreased by 25% after rosuvastatin treatment. Moreover, biliary excretion of cholesterol, phospholipids, and bile acids was increased during treatment. The results indicate that rosuvastatin treatment in ApoE*3-Leiden mice on a HFC diet leads to redistribution of cholesterol and triglycerides in the body, both by reduced hepatic VLDL production and triglyceride synthesis and by enhanced hepatobiliary removal of cholesterol, bile acids, and phospholipids, resulting in substantial reductions in plasma cholesterol and triglyceride levels. Chemicals / CAS: diacylglycerol acyltransferase, 9029-98-5; mevinolin, 75330-75-5; rosuvastatin, 147098-18-8, 147098-20-2; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins B; Apolipoproteins E; Bile Acids and Salts; Cholesterol, 57-88-5; Cholesterol, VLDL; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; RNA, Messenger; rosuvastatin, 287714-41-4; Sterols; Sulfonamides; Triglycerides
- Published
- 2005
7. Individual CLA Isomers, c9t11 and t10c12, Prevent Excess Liver Glycogen Storage and Inhibit Lipogenic Genes Expression Induced by High-Fructose Diet in Rats
- Author
-
Edyta Maslak, Antoni Szumny, Magdalena Franczyk-Zarow, Aneta Kopeć, Elzbieta Buczek, Stefan Chlopicki, Renata B. Kostogrys, Teresa Leszczyńska, and Wojciech Szczepnski
- Subjects
Very low-density lipoprotein ,food intake ,glycogen liver level ,blood biochemistry ,Conjugated linoleic acid ,cholesterol blood level ,lcsh:Medicine ,Gene Expression ,lipid blood level ,endothelial dysfunction ,fructose ,low density lipoprotein cholesterol ,chemistry.chemical_compound ,high density lipoprotein cholesterol ,monounsaturated fatty acid ,Nonalcoholic fatty liver disease ,rat ,Linoleic Acids, Conjugated ,comparative study ,fatty acid synthase ,Glycogen ,saturated fatty acid ,article ,liver cell ,food and beverages ,weight gain ,General Medicine ,polyunsaturated fatty acid ,very low density lipoprotein cholesterol ,Lipids ,vasodilatation ,unclassified drug ,Fatty acid synthase ,Cholesterol ,real time polymerase chain reaction ,glycogen ,Lipogenesis ,Saturated fatty acid ,histopathology ,lipids (amino acids, peptides, and proteins) ,t10cl2 conjugated linoleic acid ,triacylglycerol ,down regulation ,Stearoyl-CoA Desaturase ,Research Article ,fat content ,medicine.medical_specialty ,Article Subject ,n(g) nitroarginine methyl ester ,animal experiment ,lipid liver level ,lipid composition ,Fructose ,Biology ,conjugated linoleic acid ,General Biochemistry, Genetics and Molecular Biology ,animal tissue ,reverse transcription polymerase chain reaction ,body weight ,liver weight ,male ,Isomerism ,Internal medicine ,acyl coenzyme A desaturase ,nonalcoholic fatty liver ,medicine ,c9t11 conjugated linoleic acid ,Animals ,Humans ,controlled study ,Obesity ,Liver X receptor ,Triglycerides ,nonhuman ,General Immunology and Microbiology ,Rattus ,animal model ,lcsh:R ,Body Weight ,triacylglycerol blood level ,medicine.disease ,Diet ,Liver Glycogen ,Rats ,gluconeogenesis ,isomer ,Endocrinology ,chemistry ,gene expression ,biology.protein ,glycogen analysis ,control ,upregulation - Abstract
This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD) and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet. The high-fructose diet hampered body weight gain (without influencing food intake), increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), and increased saturated fatty acid (SFA) content in the liver. Both CLA isomers prevented excessive accumulation of glycogen in the liver. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved inde novolipogenesis. Although both CLA isomers (c9t11 and t10c12) display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA.
- Published
- 2014
8. Plasma and liver lipid profiles in rats exposed to chronic hypobaric hypoxia: changes in metabolic pathways
- Author
-
Ruth Pulido, Fabiola León-Velarde, Maribel Mamani, Nelson Naveas, Juan J. de la Cruz, Julio Brito, and Patricia Siques
- Subjects
Male ,purl.org/pe-repo/ocde/ford#3.03.05 [https] ,Physiology ,cholesterol blood level ,Blood lipids ,Wistar rat ,Hematocrit ,low density lipoprotein cholesterol ,Western blotting ,chemistry.chemical_compound ,Hemoglobins ,Anoxia ,HMG-CoA reductase ,high density lipoprotein cholesterol ,lipid metabolism ,animal ,rat ,Hypoxia ,hydroxymethylglutaryl coenzyme A reductase ,medicine.diagnostic_test ,biology ,messenger RNA ,purl.org/pe-repo/ocde/ford#3.01.08 [https] ,Reverse Transcriptase Polymerase Chain Reaction ,adult ,Intermittent hypoxia ,General Medicine ,biological marker ,very low density lipoprotein cholesterol ,purl.org/pe-repo/ocde/ford#3.03.11 [https] ,Up-Regulation ,SCD-1 ,chronic hypobaric hypoxia ,Cholesterol ,Liver ,Biological Markers ,lipids (amino acids, peptides, and proteins) ,triacylglycerol ,medicine.symptom ,Stearoyl-CoA Desaturase ,medicine.medical_specialty ,Scientific Articles ,stearoyl-CoA desaturase SCD-1, rat ,enzymology ,animal experiment ,Blotting, Western ,lipid liver level ,Article ,cholesterol liver level ,animal tissue ,reverse transcription polymerase chain reaction ,evaluation study ,lipid ,Internal medicine ,acyl coenzyme A desaturase ,high altitude ,medicine ,Animals ,controlled study ,Rats, Wistar ,protein expression ,Triglycerides ,hypobarism ,nonhuman ,blood lipids ,hemoglobin blood level ,Triglyceride ,hypoxia ,animal model ,Public Health, Environmental and Occupational Health ,Lipid metabolism ,hemoglobin ,Hypoxia (medical) ,triacylglycerol blood level ,Rats ,Endocrinology ,chemistry ,sterol regulatory element binding protein 1 ,Chronic Disease ,sterol regulatory element binding protein 2 ,biology.protein ,chronic hypoxia ,Hydroxymethylglutaryl CoA Reductases ,weight reduction ,metabolism ,upregulation ,Biomarkers - Abstract
Siques, Patricia, Julio Brito, Nelson Naveas, Ruth Pulido, Juan José De la Cruz, Maribel Mamani, and Fabiola León-Velarde. Plasma and liver lipid profiles in rats exposed to chronic hypobaric hypoxia: Changes in metabolic pathways. High Alt Med Biol 15:388–395, 2014.—Lipid metabolism under chronic hypoxia (CH) has not received equal attention as intermittent hypoxia (IH). To determine the CH-induced changes in plasma and liver, as well as the mRNA and protein expression of two key enzymes in the triglyceride and cholesterol biosynthesis pathways, SREBP-1 (HMG-CoA reductase) and SREBP-2 (SCD-1), we exposed adult male Wistar rats to CH (4600 m; n=15) for 30 days compared to normoxic rats (n=15). The CH rats exhibited weight loss (p
- Published
- 2014
9. PXR agonism decreases plasma HDL levels in ApoE*3-Leiden.CETP mice
- Subjects
Pregnenolone Carbonitrile ,Biomedical Research ,Scavenger Receptors ,High density lipoprotein ,Messenger ,cholesterol blood level ,Apolipoprotein E3 ,complementary DNA ,Transgenic ,pregnane X receptor ,Mice ,5 pregnen 3beta ol 20 one 16alpha carbonitrile ,cholesterol ester transfer protein ,Receptors ,Transgenic mice ,lipoprotein metabolism ,messenger RNA ,tritium ,ABC transporter A1 ,Mus ,article ,Cholesteryl ester transfer protein ,Lipids ,unclassified drug ,female ,Cholesterol ,priority journal ,Liver ,pregnenolone derivative ,lipids (amino acids, peptides, and proteins) ,cholesterol oleate ,triacylglycerol ,HDL ,Lipoproteins ,animal experiment ,Immunoblotting ,lipid liver level ,animal tissue ,reverse transcription polymerase chain reaction ,Animals ,Mus musculus ,controlled study ,Biology ,Steroid ,Triglycerides ,mouse ,plasma ,nonhuman ,triacylglycerol blood level ,Cholesterol Ester Transfer Proteins ,transgenic mouse ,gene expression ,RNA ,ATP-Binding Cassette Transporters ,Class B ,atherosclerosis ,low density lipoprotein ,polyacrylamide gel electrophoresis - Abstract
Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for human-like lipoprotein metabolism. Female mice were fed a diet with increasing amounts of the potent PXR agonist 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN). In E3L and E3L.CETP mice, PCN increased liver lipids as well as plasma cholesterol and triglycerides. However, whereas PCN increased cholesterol contained in large HDL-1 particles in E3L mice, it dose-dependently decreased HDL-cholesterol in E3L.CETP mice, indicating that CETP expression dominates the effect of PCN on HDL metabolism. Analysis of the hepatic expression of genes involved in HDL metabolism showed that PCN decreased expression of genes involved in HDL synthesis (Abca1, Apoa1), maturation (Lcat, Pltp) and clearance (Sr-b1). The HDL-increasing effect of PCN, observed in E3L mice, is likely caused by a marked decrease in hepatic SR-BI protein expression, and completely reversed by CETP expression. We conclude that chronic PXR agonism dose-dependently reduces plasma HDL-cholesterol in the presence of CETP. © 2008 Elsevier B.V. All rights reserved.
- Published
- 2009
10. PXR agonism decreases plasma HDL levels in ApoE*3-Leiden.CETP mice
- Author
-
Haan, W. de, Vries-van der Weij, J. de, Mol, I.M., Hoekstra, M., Romijn, J.A., Jukema, J.W., Havekes, L.M., Princen, H.M.G., Rensen, P.C.N., and TNO Kwaliteit van Leven
- Subjects
Pregnenolone Carbonitrile ,Receptors, Steroid ,Biomedical Research ,High density lipoprotein ,cholesterol blood level ,Apolipoprotein E3 ,complementary DNA ,pregnane X receptor ,Mice ,5 pregnen 3beta ol 20 one 16alpha carbonitrile ,cholesterol ester transfer protein ,Transgenic mice ,lipoprotein metabolism ,messenger RNA ,tritium ,ABC transporter A1 ,Mus ,article ,Scavenger Receptors, Class B ,Cholesteryl ester transfer protein ,Lipids ,unclassified drug ,female ,priority journal ,Liver ,pregnenolone derivative ,lipids (amino acids, peptides, and proteins) ,cholesterol oleate ,triacylglycerol ,Lipoproteins ,animal experiment ,Immunoblotting ,lipid liver level ,Mice, Transgenic ,animal tissue ,reverse transcription polymerase chain reaction ,Animals ,Mus musculus ,controlled study ,RNA, Messenger ,Biology ,Triglycerides ,mouse ,plasma ,nonhuman ,Cholesterol, HDL ,cholesterol ,triacylglycerol blood level ,Cholesterol Ester Transfer Proteins ,transgenic mouse ,gene expression ,ATP-Binding Cassette Transporters ,atherosclerosis ,low density lipoprotein ,polyacrylamide gel electrophoresis - Abstract
Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for human-like lipoprotein metabolism. Female mice were fed a diet with increasing amounts of the potent PXR agonist 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN). In E3L and E3L.CETP mice, PCN increased liver lipids as well as plasma cholesterol and triglycerides. However, whereas PCN increased cholesterol contained in large HDL-1 particles in E3L mice, it dose-dependently decreased HDL-cholesterol in E3L.CETP mice, indicating that CETP expression dominates the effect of PCN on HDL metabolism. Analysis of the hepatic expression of genes involved in HDL metabolism showed that PCN decreased expression of genes involved in HDL synthesis (Abca1, Apoa1), maturation (Lcat, Pltp) and clearance (Sr-b1). The HDL-increasing effect of PCN, observed in E3L mice, is likely caused by a marked decrease in hepatic SR-BI protein expression, and completely reversed by CETP expression. We conclude that chronic PXR agonism dose-dependently reduces plasma HDL-cholesterol in the presence of CETP. © 2008 Elsevier B.V. All rights reserved.
- Published
- 2009
11. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity
- Author
-
Pols, T.W.H., Ottenhoff, R., Vos, M., Levels, J.H.M., Quax, P.H.A., Meijers, J.C.M., Pannekoek, H., Groen, A.K., Vries, C.J.M. de, and TNO Kwaliteit van Leven
- Subjects
Male ,Receptors, Steroid ,NR4A1 ,Receptors, Cytoplasmic and Nuclear ,genetic analysis ,lipid blood level ,enzyme repression ,Mice ,Nur77 ,lipid metabolism ,fatty acid synthase ,Mus ,adenovirus vector ,article ,acyl coenzyme A desaturase 1 ,protein function ,low density lipoprotein receptor ,SREBP1c ,glycerol 3 phosphate acyltransferase ,sterol regulatory element binding protein 1c ,enzyme activity ,DNA-Binding Proteins ,Sterol regulatory element binding protein-1 ,priority journal ,Liver ,ABC transporter ,triacylglycerol ,Sterol Regulatory Element Binding Protein 1 ,animal experiment ,lipid liver level ,animal tissue ,Adenoviridae ,acyl coenzyme A desaturase ,Animals ,controlled study ,RNA, Messenger ,ABC transporter G5 ,Biology ,protein expression ,mouse ,Triglycerides ,nonhuman ,ABC transporter G8 ,NR4A nuclear receptors ,nucleotide sequence ,nuclear receptor Nur77 ,Mice, Inbred C57BL ,Gene Expression Regulation ,gene expression ,Transcription Factors - Abstract
NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity. © 2007 Elsevier Inc. All rights reserved. Chemicals / CAS: acyl coenzyme A desaturase, 9014-34-0; fatty acid synthase, 9045-77-6; glycerol 3 phosphate acyltransferase, 9029-96-3; DNA-Binding Proteins; orphan nuclear receptor NGFI-B, 121479-42-3; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Triglycerides
- Published
- 2008
12. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity
- Subjects
Male ,Cytoplasmic and Nuclear ,Messenger ,NR4A1 ,genetic analysis ,lipid blood level ,Inbred C57BL ,enzyme repression ,Mice ,Nur77 ,lipid metabolism ,Receptors ,fatty acid synthase ,Mus ,adenovirus vector ,article ,acyl coenzyme A desaturase 1 ,protein function ,low density lipoprotein receptor ,SREBP1c ,glycerol 3 phosphate acyltransferase ,sterol regulatory element binding protein 1c ,enzyme activity ,DNA-Binding Proteins ,Sterol regulatory element binding protein-1 ,priority journal ,Liver ,ABC transporter ,triacylglycerol ,Sterol Regulatory Element Binding Protein 1 ,animal experiment ,lipid liver level ,animal tissue ,Adenoviridae ,acyl coenzyme A desaturase ,Animals ,controlled study ,ABC transporter G5 ,Biology ,protein expression ,Steroid ,mouse ,Triglycerides ,nonhuman ,ABC transporter G8 ,NR4A nuclear receptors ,nucleotide sequence ,nuclear receptor Nur77 ,Gene Expression Regulation ,gene expression ,RNA ,Transcription Factors - Abstract
NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity. © 2007 Elsevier Inc. All rights reserved. Chemicals / CAS: acyl coenzyme A desaturase, 9014-34-0; fatty acid synthase, 9045-77-6; glycerol 3 phosphate acyltransferase, 9029-96-3; DNA-Binding Proteins; orphan nuclear receptor NGFI-B, 121479-42-3; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Triglycerides
- Published
- 2008
13. Chronic black tea administration protects plasma proteins, plasma, liver and kidney lipids against oxidation
- Author
-
Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji ve Genetik Anabilim Dalı., Sürmen-Gür, Esma, Gülten, Tuna, Serdar, Zehra, Çolakoğulları, Mukaddes, AAG-7327-2021, and AAH-6200-2021
- Subjects
Male ,Intestine brush border ,Supplementation ,Tissue lipid peroxidation ,Kidney ,Ileum mucosa ,Antioxidants ,Animal tissue ,Plasma lipid peroxidation ,Plasma ,Malondialdehyde ,kidney ,Flavanols ,White Tea ,Epigallocatechin Gallate ,Chronic drug administration ,Blood proteins ,Lipid liver level ,Malonaldehyde ,Correlation analysis ,Glutathione ,Lipids ,Lipid oxidation ,Cellular immunity ,Liver ,Carbonyl derivative ,Thiobarbituric acid reactive substances ,Jejunum mucosa ,Black tea extract ,Lipid peroxidation ,Research & experimental medicine ,Theaflavins ,Random allocation ,Article ,Protein metabolism ,Tissue level ,Antioxidant activity ,Oxidation ,Animals ,Animal experiment ,Medicine, research & experimental ,Tea ,DNA-damage ,Administration, oral ,Water ,Plant extracts ,Nonhuman ,Rats ,Plasma protein ,Green ,Sprague-dawley ,Blood level ,Rat ,Reference standards ,Protein oxidation ,Controlled study - Abstract
Background: Black tea is known to have protective effects against plasma lipid and lipoprotein oxidation, but its influence on lipid peroxidation in tissue has been less studied. The effect of oral black tea consumption on protein oxidation has also not been demonstrated. The present study investigated the antioxidant effects of oral black tea consumption. Material/Methods: Male Sprague-Dawley rats were fed a regular murine chow diet. The controls were supplied With water ad libitum, while the black tea group received aqueous black tea extract as the sole source of liquids. At the end of the ten-week experimental period, intestinal brush border, liver and kidney reduced-glutathione concentrations were evaluated as an index of cellular antioxidant defence. Plasma and tissue malondialdehyde concentrations and plasma protein carbonyl content were measured to evaluate lipid peroxidation and protein oxidation, respectively. Results: The plasma malondialclehyde and protein carbonyl contents of rats consuming the black tea were significantly less than in controls. Similarly, liver and kidney malondialdehyde concentrations were significantly lower in the experimental group, while jejunoileal mucosa were not affected. Ten weeks of black tea administration caused significantly higher reduced-glutathione levels in the kidneys of black tea-administered rats, and a significant negative correlation was observed between kidney malondialdehyde and glutathione concentrations. Conclusions: These findings provide evidence that long term black tea supplementation is capable of protecting both plasma proteins and plasma lipids from oxidative injury, and demonstrate that chronic black tea administration protects both liver and kidney tissues - but not the jejunoileal mucosa against oxidation.
- Published
- 2006
14. Rosuvastatin reduces plasma lipids by inhibiting VLDL production and enhancing hepatobiliary lipid excretion in ApoE*3-Leiden mice
- Subjects
Biomedical Research ,Messenger ,cholesterol blood level ,Apolipoprotein E3 ,lipid blood level ,biliary excretion ,cholesterol diet ,Transgenic ,hydroxymethylglutaryl coenzyme A reductase inhibitor ,Feces ,Mice ,Bile ,rat ,statistical significance ,Chromatography ,Sulfonamides ,Reverse Transcriptase Polymerase Chain Reaction ,mevinolin ,enzyme activity ,very low density lipoprotein ,Sterols ,Cholesterol ,priority journal ,Liver ,High Pressure Liquid ,lipids (amino acids, peptides, and proteins) ,Female ,VLDL ,lipid diet ,Lipoproteins ,lipid liver level ,lipid composition ,animal tissue ,Bile Acids and Salts ,Apolipoproteins E ,Animals ,controlled study ,phospholipid ,mouse ,Triglycerides ,hepatobiliary system ,Apolipoproteins B ,nonhuman ,nutritional and metabolic diseases ,Statin ,triacylglycerol blood level ,Fluorobenzenes ,Lipid metabolism ,Pyrimidines ,cholesterol synthesis ,gene expression ,lipolysis ,RNA ,diacylglycerol acyltransferase ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,rosuvastatin - Abstract
The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (O [control], 0.00125%, 0.0025%, or 0.005% [w/w]) or 0.05% (w/w) lovastatin. The highest dose of rosuvastatin reduced plasma cholesterol and triglyceride levels by 39% and 42%, respectively, compared with the HFC control. Lovastatin had no effect on plasma cholesterol and triglyceride levels. In ApoE*3-Leiden mice on a chow diet, rosuvastatin (0.005% [w/w]) decreased plasma cholesterol levels by 35% without having an effect on triglyceride levels. On a chow diet, expression of genes involved in cholesterol biosynthesis and uptake in the liver was increased by rosuvastatin. Further mechanistic studies in HFC-fed mice showed that rosuvastatin treatment resulted in decreased hepatic VLDL-triglyceride and VLDL-apolipoprotein B production. VLDL lipid composition remained unchanged, indicating a reduction in the number of VLDL particles secreted. Lipolytic activity and expression of genes involved in cholesterol and triglyceride synthesis and β-oxidation of fatty acids in the liver were not affected by rosuvastatin treatment, and hepatic lipid content did not change. However, activity of hepatic diacylglycerol acyltransferase was significantly decreased by 25% after rosuvastatin treatment. Moreover, biliary excretion of cholesterol, phospholipids, and bile acids was increased during treatment. The results indicate that rosuvastatin treatment in ApoE*3-Leiden mice on a HFC diet leads to redistribution of cholesterol and triglycerides in the body, both by reduced hepatic VLDL production and triglyceride synthesis and by enhanced hepatobiliary removal of cholesterol, bile acids, and phospholipids, resulting in substantial reductions in plasma cholesterol and triglyceride levels. Chemicals / CAS: diacylglycerol acyltransferase, 9029-98-5; mevinolin, 75330-75-5; rosuvastatin, 147098-18-8, 147098-20-2; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins B; Apolipoproteins E; Bile Acids and Salts; Cholesterol, 57-88-5; Cholesterol, VLDL; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; RNA, Messenger; rosuvastatin, 287714-41-4; Sterols; Sulfonamides; Triglycerides
- Published
- 2005
15. Lipid atherogenic risk markers can be more favourably influenced by the cis-9,trans-11-octadecadienoate isomer than a conjugated linoleic acid mixture or fish oil in hamsters
- Author
-
Jean-Charles Martin, Marie-France Blouquit, Colette Sérougne, Maamar Souidi, Karine Valeille, Michel Riottot, Daniel Gripois, Jean-Christophe Bouthegourd, Arilait Recherches, Université Paris Sud Orsay, and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
- Subjects
Blood Glucose ,Male ,Apolipoprotein B ,Conjugated ,030309 nutrition & dietetics ,Arteriosclerosis ,Conjugated linoleic acid ,[SDV]Life Sciences [q-bio] ,cholesterol blood level ,Medicine (miscellaneous) ,11 linoleic acid ,cholesterol diet ,fish oil ,low density lipoprotein cholesterol ,scavenger receptor ,chemistry.chemical_compound ,Feces ,0302 clinical medicine ,high density lipoprotein cholesterol ,Risk Factors ,insulin resistance ,Cricetinae ,homeostasis ,Receptors ,apolipoprotein B ,Bile ,Insulin ,Linoleic Acids, Conjugated ,animal ,Food science ,Lipoprotein ,sterol excretion ,apolipoprotein E ,0303 health sciences ,Unsaturated ,Nutrition and Dietetics ,biology ,integumentary system ,lipoprotein receptor ,Rumenic acid ,article ,gallstone ,food and beverages ,atherogenesis ,risk assessment ,Fish oil ,biological marker ,Biochemistry ,fatty acid derivative ,risk factor ,Linoleic Acids ,Liver ,diet supplementation ,lipids (amino acids, peptides, and proteins) ,Biological Markers ,conjugation ,linoleic acid ,lipid binding protein ,Linoleic acid ,enzymology ,030209 endocrinology & metabolism ,11-linoleic acid ,lipid liver level ,chemistry ,receptor subtype ,conjugated linoleic acid ,animal tissue ,03 medical and health sciences ,Insulin resistance ,Fish Oils ,Dietary Fats, Unsaturated ,lipid ,blood ,medicine ,feces analysis ,Animals ,controlled study ,Receptors, Lipoprotein ,nonhuman ,medicine.disease ,Lipid Metabolism ,Dietary Fats ,Sterol ,hamster ,cis trans isomerism ,glucose blood level ,biochemical marker ,edible oil ,biology.protein ,metabolism ,Biomarkers - Abstract
The aim of our present study was to compare the efficiency of conjugated linoleic acids (CLA) and fish oil in modulating atherogenic risk markers. Adult male hamsters were given a cholesterol-rich diet (0·6 g/kg) for 8 weeks; the diet was supplemented with 5 gcis-9,trans-11-CLA isomer/kg, 12 g CLA mixture (CLA-mix)/kg, 12 g fish oil/kg or 12 g fish oil + 12 g CLA-mix/kg. The plasma cholesterol status was improved only with thecis-9,trans-11-CLA (HDL-cholesterol and HDL-cholesterol:LDL-cholesterol ratio,PP=0·06), with an increase (33–40 %) in the liver lipoprotein receptors (scavenger receptor-type I and LDL ApoB/E receptor) and HDL-binding protein 2 (PP=−0·031). In comparison, fish-oil feeding alone improved merely the scavenger receptor-type I and HDL-binding protein 2 liver status and faeces sterol output. For most of our present observations, the concomitant intake of fish oil and CLA-mix gave dominant effects that were exclusive and specific to one or the other oil. In conclusion, part of the beneficial effects of CLA in the present study can be ascribed to thecis-9,trans-11-isomer, and these did not generally overlap with those of fish oil. In addition, the CLA-mix effects are clearly affected by the marine (n-3) fatty acids.
- Published
- 2004
16. Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons from Animal Models
- Subjects
Biomedical Research ,Mouse ,Hyperlipidemias ,Mouse models ,Triacylglycerol ,Partition coefficient ,Pathophysiology ,Mice ,Disease association ,Lnsulin resistance ,Dogs ,Genetic ,Metabolic syndrome X ,Models ,Endocrine system ,Diabetes Mellitus ,Animals ,Homeostasis ,Humans ,Animal model ,Animal experiment ,Obesity ,Biology ,Triglycerides ,Lipoprotein metabolism ,Glucose metabolism ,Rodent ,Genetic transcription ,Animal ,Lipid liver level ,Fatty Acids ,Insulin resistance ,Nonhuman ,Biological ,Rats ,Fatty Liver ,Glucose ,Dyslipidemia ,Adipose Tissue ,Liver ,Zucker ,Fatty acid metabolism ,Non insulin dependent diabetes mellitus ,Alcohol ,Transcription ,Type 2 ,Short survey - Abstract
Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the liver as part of this syndrome. In this review, important principles of the pathophysiological involvement of the liver in the metabolic syndrome obtained in rodent models are summarized. We focus on non-alcoholic causes of steatosis, because the animal experiments we refer to did not include alcohol as an experimental condition. In general, there is continuous cycling and redistribution of non-oxidized fatty acids between different organs. The amount of TG in an intrinsically normal liver is not fixed but can readily be increased by nutritional, metabolic, and endocrine interactions involving TG/free fatty acid (FFA) partitioning and TG/FFA metabolism. Several lines of evidence indicate that hepatic TG accumulation is also a causative factor involved in hepatic insulin resistance. Complex interactions between endocrine, metabolic, and transcriptional pathways are involved in TG-induced hepatic insulin resistance. Therefore, the liver participates passively and actively in the metabolic derangements of the metabolic syndrome. We speculate that similar mechanisms may also be involved in human pathophysiology. Chemicals / CAS: alcohol, 64-17-5; Fatty Acids; Glucose, 50-99-7; Triglycerides
- Published
- 2004
17. Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons from Animal Models
- Author
-
Folkert Kuipers, Johannes A. Romijn, Louis M. Havekes, Peter J. Voshol, M. den Boer, TNO Preventie en Gezondheid, Other departments, and Center for Liver, Digestive and Metabolic Diseases (CLDM)
- Subjects
Biomedical Research ,Mouse ,Transcription, Genetic ,ACTIVATED RECEPTOR-GAMMA ,medicine.medical_treatment ,Mouse models ,Partition coefficient ,chemistry.chemical_compound ,Mice ,Lnsulin resistance ,Endocrine system ,Homeostasis ,Metabolic Syndrome ,INSULIN-RESISTANCE ,Glucose metabolism ,Rodent ,NONALCOHOLIC STEATOHEPATITIS ,Genetic transcription ,Lipid liver level ,Fatty liver ,Fatty Acids ,Adipose Tissue ,Liver ,Lipogenesis ,Models, Animal ,VLDL PRODUCTION ,Cardiology and Cardiovascular Medicine ,Alcohol ,medicine.medical_specialty ,HORMONE-SENSITIVE LIPASE ,LIPOPROTEIN-LIPASE ,Hyperlipidemias ,Biology ,Triacylglycerol ,Pathophysiology ,Models, Biological ,Insulin resistance ,Disease association ,Dogs ,Metabolic syndrome X ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Animal model ,Animal experiment ,Obesity ,DE-NOVO LIPOGENESIS ,Triglycerides ,Lipoprotein metabolism ,Fatty acid metabolism ,Insulin ,DIABETES-MELLITUS ,medicine.disease ,Nonhuman ,Rats ,Rats, Zucker ,Fatty Liver ,Endocrinology ,Glucose ,chemistry ,Dyslipidemia ,Diabetes Mellitus, Type 2 ,RISK-FACTORS ,Non insulin dependent diabetes mellitus ,Steatosis ,Metabolic syndrome ,Short survey - Abstract
Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the liver as part of this syndrome. In this review, important principles of the pathophysiological involvement of the liver in the metabolic syndrome obtained in rodent models are summarized. We focus on non-alcoholic causes of steatosis, because the animal experiments we refer to did not include alcohol as an experimental condition. In general, there is continuous cycling and redistribution of non-oxidized fatty acids between different organs. The amount of TG in an intrinsically normal liver is not fixed but can readily be increased by nutritional, metabolic, and endocrine interactions involving TG/free fatty acid (FFA) partitioning and TG/FFA metabolism. Several lines of evidence indicate that hepatic TG accumulation is also a causative factor involved in hepatic insulin resistance. Complex interactions between endocrine, metabolic, and transcriptional pathways are involved in TG-induced hepatic insulin resistance. Therefore, the liver participates passively and actively in the metabolic derangements of the metabolic syndrome. We speculate that similar mechanisms may also be involved in human pathophysiology. Chemicals / CAS: alcohol, 64-17-5; Fatty Acids; Glucose, 50-99-7; Triglycerides
- Published
- 2004
18. Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice
- Subjects
Blood Glucose ,Male ,Enzyme mechanism ,Unclassified drug ,Mouse ,Glucose transport ,Lipolysis ,Knockout ,Triacylglycerol ,Animal tissue ,Western blotting ,Hyperinsulinemia ,Mice ,Knockout mouse ,Protein kinase B ,Animals ,Insulin ,Enzyme activity ,Hormone sensitivity ,Enzyme deficiency ,Triglycerides ,Enzyme phosphorylation ,Lipid liver level ,Fatty Acids ,Gluconeogenesis ,food and beverages ,Proteins ,Fasting ,Skeletal ,Insulin sensitivity ,Nonhuman ,Cholesterol Esterase ,Glucose ,Hormone sensitive lipase ,Cholesterol ,Liver ,Health ,Triacylglycerol lipase ,Fatty acid blood level ,Nonesterified ,Intercellular Signaling Peptides and Proteins ,Muscle ,Adiponectin ,Controlled study ,Insulin receptor ,Receptor - Abstract
Hormone-sensitive lipase (HSL) is a major enzyme for triglyceride (TG) lipolysis in adipose tissue. In HSL-knockout mice, plasma free fatty acid and TG levels are low, associated with low liver TG content. Because a decreased hepatic insulin sensitivity has been reported to be associated with high liver TG levels, our aim was to determine whether a hepatic TG content lower than normal, as observed in HSL-knockout mice, leads to increased hepatic insulin sensitivity. Therefore, hyperinsulinemic clamp experiments in combination with D-3H. glucose were used. Furthermore, hepatic insulin receptor and phosphorylated protein kinase B (PKB-P)/akt were analyzed by Western blotting. No significant differences where observed in insulin-mediated whole-body glucose uptake between HSL-knockout and control mice. Interestingly, hepatic insulin sensitivity of HSL-knockout mice was increased, because insulin caused a greater reduction in endogenous glucose production (∼71% compared with ∼31% in control mice; P < 0.05), despite decreased plasma adiponectin levels. PKB/akt phosphorylation and phosphatidylinositol-3-kinase activity was significantly higher in livers of HSL-knockout mice after insulin stimulation. In HSL-knockout mice, reduced hepatic TG stores result in an increased suppressive effect of insulin on hepatic glucose production, in line with an increased hepatic PKB-P/akt and phosphatidylinositol-3 kinase activity. Thus, hepatic insulin sensitivity is indeed increased after reducing hepatic TG stores below normal.
- Published
- 2003
19. Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice
- Author
-
Voshol, P.J., Haemmerle, G., Ouwens, D.M., Zimmermann, R., Zechner, R., Teusink, B., Maassen, J.A., Havekes, L.M., and Romijn, J.A.
- Subjects
Blood Glucose ,Male ,Enzyme mechanism ,Unclassified drug ,Mouse ,Glucose transport ,Lipolysis ,Fatty Acids, Nonesterified ,Triacylglycerol ,Animal tissue ,Western blotting ,Hyperinsulinemia ,Mice ,Knockout mouse ,Protein kinase B ,Animals ,Insulin ,Enzyme activity ,Hormone sensitivity ,Muscle, Skeletal ,Enzyme deficiency ,Triglycerides ,Mice, Knockout ,Enzyme phosphorylation ,Lipid liver level ,Gluconeogenesis ,food and beverages ,Proteins ,Fasting ,Insulin sensitivity ,Nonhuman ,Receptor, Insulin ,Cholesterol Esterase ,Glucose ,Hormone sensitive lipase ,Cholesterol ,Liver ,Health ,Triacylglycerol lipase ,Fatty acid blood level ,Intercellular Signaling Peptides and Proteins ,Adiponectin ,Controlled study ,Insulin receptor - Abstract
Hormone-sensitive lipase (HSL) is a major enzyme for triglyceride (TG) lipolysis in adipose tissue. In HSL-knockout mice, plasma free fatty acid and TG levels are low, associated with low liver TG content. Because a decreased hepatic insulin sensitivity has been reported to be associated with high liver TG levels, our aim was to determine whether a hepatic TG content lower than normal, as observed in HSL-knockout mice, leads to increased hepatic insulin sensitivity. Therefore, hyperinsulinemic clamp experiments in combination with D-3H. glucose were used. Furthermore, hepatic insulin receptor and phosphorylated protein kinase B (PKB-P)/akt were analyzed by Western blotting. No significant differences where observed in insulin-mediated whole-body glucose uptake between HSL-knockout and control mice. Interestingly, hepatic insulin sensitivity of HSL-knockout mice was increased, because insulin caused a greater reduction in endogenous glucose production (∼71% compared with ∼31% in control mice; P < 0.05), despite decreased plasma adiponectin levels. PKB/akt phosphorylation and phosphatidylinositol-3-kinase activity was significantly higher in livers of HSL-knockout mice after insulin stimulation. In HSL-knockout mice, reduced hepatic TG stores result in an increased suppressive effect of insulin on hepatic glucose production, in line with an increased hepatic PKB-P/akt and phosphatidylinositol-3 kinase activity. Thus, hepatic insulin sensitivity is indeed increased after reducing hepatic TG stores below normal.
- Published
- 2003
20. Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons from Animal Models
- Author
-
Boer, M. den, Voshol, P.J., Kuipers, F., Havekes, L.M., Romijn, J.A., Boer, M. den, Voshol, P.J., Kuipers, F., Havekes, L.M., and Romijn, J.A.
- Abstract
Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the liver as part of this syndrome. In this review, important principles of the pathophysiological involvement of the liver in the metabolic syndrome obtained in rodent models are summarized. We focus on non-alcoholic causes of steatosis, because the animal experiments we refer to did not include alcohol as an experimental condition. In general, there is continuous cycling and redistribution of non-oxidized fatty acids between different organs. The amount of TG in an intrinsically normal liver is not fixed but can readily be increased by nutritional, metabolic, and endocrine interactions involving TG/free fatty acid (FFA) partitioning and TG/FFA metabolism. Several lines of evidence indicate that hepatic TG accumulation is also a causative factor involved in hepatic insulin resistance. Complex interactions between endocrine, metabolic, and transcriptional pathways are involved in TG-induced hepatic insulin resistance. Therefore, the liver participates passively and actively in the metabolic derangements of the metabolic syndrome. We speculate that similar mechanisms may also be involved in human pathophysiology. Chemicals / CAS: alcohol, 64-17-5; Fatty Acids; Glucose, 50-99-7; Triglycerides
- Published
- 2004
21. Effect of D-tagatose on liver weight and glycogen content of rats
- Subjects
Male ,Electron ,Animal tissue ,Eating ,Dose response ,Animals ,Animal model ,Animal experiment ,Tagatose ,Cecum ,Nutrition ,Priority journal ,Hexoses ,Cell Nucleus ,Microscopy ,DNA synthesis ,Lipid liver level ,Body Weight ,DNA ,Organ Size ,Lipid ,Nonhuman ,Glycogen liver level ,Liver weight ,Liver Glycogen ,Rats ,Liver ,DNA content ,Sweetening Agents ,Acyl coenzyme a oxidase ,Toxicity testing ,Rat ,Liver protein ,Peroxisome Proliferators ,Lauric acid derivative ,Sprague-Dawley ,Animal cell ,Controlled study ,Glycogen - Abstract
D-Tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations. To determine whether there might be any toxicological relevance to this effect, three studies were conducted in male, adult Sprague-Dawley rats. In the first study, four groups received Purina diet (group A), Purina diet with 20% D-tagatose (group B), SDS diet (group C), or SDS diet with 20% D-tagatose (group D). For groups A and B, the 28-day treatment period was followed by a 14-day recovery period (Purina diet). Food remained available to all animals until the time of sacrifice. Groups of 10 rats were killed on days 14 (groups A and B), 28 (groups A-D), and 42 (groups A and B). Body weights, as well as weights of wet and lyophilized livers, were determined. The lyophilized livers collected on day 28 from groups A and B were analyzed for protein, total lipid, glycogen, DNA, and residual moisture. By day 14, relative wet liver weights had increased by 23% in group B. On day 28, the increase was 38% in group B and 44% in group D. At the end of the recovery period, the increase had diminished to 14% in group B. On day 28, liver glycogen content (in %) was significantly increased, and liver protein, lipid, and DNA contents were significantly decreased in group B compared to group A. Total amounts per liver of protein, total lipid, glycogen, and DNA were significantly increased. In the second study, four groups of 20 rats each received SDS diet with 0, 5, 10, and 20% D-tagatose for 29-31 days. The food was available until the time of sacrifice. At termination, plasma was obtained from 10 rats/group for clinicochemical analyses. Five rats/group were subjected to whole-body perfusion, followed by processing of livers for qualitative and quantitative electron microscopic examination. Livers of 6 rats/group were analyzed for acyl-CoA oxidase and laurate 12-hydroxylase (cytochrome P450 4A1) activity, DNA synthesis (Ki-67 index), and number of nuclei per unit area of tissue. Liver weights were significantly increased in linear relation to the D-tagatose intake. Plasma transaminases (but not glutamyl transferase and alkaline phosphatase) were increased in the high-dose group. Except for glycogen accumulation, no ultrastructural changes were seen on electron microscopic examination of livers of the control and high-dose groups. Morphometric analysis confirmed the increase of glycogen and the absence of alterations of endoplasmatic reticulum, mitochondria, and Golgi apparatus. The Ki-67 index did not differ between the groups. A dose-related decrease of the number of nuclei per unit area signified some hepatocellular hypertrophy. Acyl-CoA oxidase and CYP4A1 activity were significantly increased in the mid- and high-dose groups, but these increases were small and not accompanied by electron-microscopic evidence of peroxisome proliferation. In the third study, four groups received SDS diet (groups A and C) or SDS diet with 5% D-tagatose (groups B and D). All animals were killed on day 28. Groups A and B were fasted for 24 h before sacrifice; groups C and D had food available until sacrifice. Liver weights and liver composition were measured as in Study 1. Relative wet and dry liver weights were increased in response to the treatment in rats killed under the fed condition, but not in rats killed under the fasted condition. The livers of the treated rats (group D) had an increased glycogen content in comparison to the controls (group C). Taken together, these results demonstrate that D-tagatose at dietary levels of 5-20% increases liver glycogen deposition and relative liver weights in nonfasting rats. In fasted rats the 5% dose level is the no-effect level. At the higher dose levels, the increased glycogen deposition induced minimal hypertrophy and some compensatory growth which reached completion before the end of the 28-day treatment period. It is concluded that the liver enlargement seen in response to the consumption of D-tagatose is a physiological response to the treatment-induced increased glycogen deposition. No hepatocellular growth was seen at the 5% dietary level of D-tagatose (corresponding to an intake of 2.6-2.8 g/kg body wt), suggesting that the increase of liver glycogen at this dose remained within normal limits. © 1999 Academic Press.
- Published
- 1999
22. Effect of d-tagatose on liver weight and glycogen content of rats
- Author
-
Bär, A., Lina, B.A.R., Groot, D.M.G. de, Bie, B. de, Appel, M.J., and Centraal Instituut voor Voedingsonderzoek TNO
- Subjects
Male ,Animal tissue ,Rats, Sprague-Dawley ,Eating ,Dose response ,Animals ,Animal model ,Animal experiment ,Tagatose ,Cecum ,Nutrition ,Priority journal ,Hexoses ,Cell Nucleus ,DNA synthesis ,Lipid liver level ,Body Weight ,DNA ,Organ Size ,Lipid ,Nonhuman ,Glycogen liver level ,Liver weight ,Liver Glycogen ,Rats ,Microscopy, Electron ,Liver ,DNA content ,Sweetening Agents ,Acyl coenzyme a oxidase ,Toxicity testing ,Rat ,Liver protein ,Peroxisome Proliferators ,Lauric acid derivative ,Animal cell ,Controlled study ,Glycogen - Abstract
D-Tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations. To determine whether there might be any toxicological relevance to this effect, three studies were conducted in male, adult Sprague-Dawley rats. In the first study, four groups received Purina diet (group A), Purina diet with 20% D-tagatose (group B), SDS diet (group C), or SDS diet with 20% D-tagatose (group D). For groups A and B, the 28-day treatment period was followed by a 14-day recovery period (Purina diet). Food remained available to all animals until the time of sacrifice. Groups of 10 rats were killed on days 14 (groups A and B), 28 (groups A-D), and 42 (groups A and B). Body weights, as well as weights of wet and lyophilized livers, were determined. The lyophilized livers collected on day 28 from groups A and B were analyzed for protein, total lipid, glycogen, DNA, and residual moisture. By day 14, relative wet liver weights had increased by 23% in group B. On day 28, the increase was 38% in group B and 44% in group D. At the end of the recovery period, the increase had diminished to 14% in group B. On day 28, liver glycogen content (in %) was significantly increased, and liver protein, lipid, and DNA contents were significantly decreased in group B compared to group A. Total amounts per liver of protein, total lipid, glycogen, and DNA were significantly increased. In the second study, four groups of 20 rats each received SDS diet with 0, 5, 10, and 20% D-tagatose for 29-31 days. The food was available until the time of sacrifice. At termination, plasma was obtained from 10 rats/group for clinicochemical analyses. Five rats/group were subjected to whole-body perfusion, followed by processing of livers for qualitative and quantitative electron microscopic examination. Livers of 6 rats/group were analyzed for acyl-CoA oxidase and laurate 12-hydroxylase (cytochrome P450 4A1) activity, DNA synthesis (Ki-67 index), and number of nuclei per unit area of tissue. Liver weights were significantly increased in linear relation to the D-tagatose intake. Plasma transaminases (but not glutamyl transferase and alkaline phosphatase) were increased in the high-dose group. Except for glycogen accumulation, no ultrastructural changes were seen on electron microscopic examination of livers of the control and high-dose groups. Morphometric analysis confirmed the increase of glycogen and the absence of alterations of endoplasmatic reticulum, mitochondria, and Golgi apparatus. The Ki-67 index did not differ between the groups. A dose-related decrease of the number of nuclei per unit area signified some hepatocellular hypertrophy. Acyl-CoA oxidase and CYP4A1 activity were significantly increased in the mid- and high-dose groups, but these increases were small and not accompanied by electron-microscopic evidence of peroxisome proliferation. In the third study, four groups received SDS diet (groups A and C) or SDS diet with 5% D-tagatose (groups B and D). All animals were killed on day 28. Groups A and B were fasted for 24 h before sacrifice; groups C and D had food available until sacrifice. Liver weights and liver composition were measured as in Study 1. Relative wet and dry liver weights were increased in response to the treatment in rats killed under the fed condition, but not in rats killed under the fasted condition. The livers of the treated rats (group D) had an increased glycogen content in comparison to the controls (group C). Taken together, these results demonstrate that D-tagatose at dietary levels of 5-20% increases liver glycogen deposition and relative liver weights in nonfasting rats. In fasted rats the 5% dose level is the no-effect level. At the higher dose levels, the increased glycogen deposition induced minimal hypertrophy and some compensatory growth which reached completion before the end of the 28-day treatment period. It is concluded that the liver enlargement seen in response to the consumption of D-tagatose is a physiological response to the treatment-induced increased glycogen deposition. No hepatocellular growth was seen at the 5% dietary level of D-tagatose (corresponding to an intake of 2.6-2.8 g/kg body wt), suggesting that the increase of liver glycogen at this dose remained within normal limits. © 1999 Academic Press.
- Published
- 1999
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.