RESUMO
Anorexia in obese cats may result in feline hepatic lipidosis (FHL). This study was designed to determine plasma lipids and lipoprotein profiles in queens at different stages during experimental induction of FHL (lean, obese, FHL), and after 10 weeks of treatment. Results were compared with those obtained from lean queens of same age fed the same diet but at a maintenance level, once a day. Hepatic lipidosis led to an increase in plasma triacylglycerol (TG), very low density lipoprotein (VLDL) and low density lipoprotein (LDL), and an enrichment of LDL with TG and of high density lipoprotein (HDL) with cholesterol, suggesting that VLDL secretion is enhanced, VLDL and LDL catabolism is lowered, and lipoprotein exchanges are impaired in FHL. This study also showed that cholesterolaemia is increased in cats fed at a dietary rhythm of one meal per day compared to ad libitum feeding.
Assuntos
Ração Animal , Doenças do Gato/sangue , Lipidoses/veterinária , Lipídeos/sangue , Lipoproteínas/sangue , Obesidade/veterinária , Fenômenos Fisiológicos da Nutrição Animal , Animais , Anorexia/complicações , Anorexia/veterinária , Doenças do Gato/etiologia , Doenças do Gato/metabolismo , Gatos , Colesterol/sangue , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/veterinária , Feminino , Lipidoses/sangue , Lipidoses/etiologia , Lipidoses/metabolismo , Lipoproteínas/química , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Obesidade/sangue , Obesidade/complicações , Obesidade/metabolismo , Distribuição Aleatória , Organismos Livres de Patógenos Específicos , Triglicerídeos/sangueRESUMO
The effects of an induced hyperinsulinemia on both the cholesterol and bile acid metabolisms were analyzed in the hamster. The role of dietary sucrose as modulator of these effects was evaluated by feeding the animals with two semi-synthetic diets containing a low (SD, 20%) and a high (LD, 62.5%) sucrose proportion. Hamsters fed under basal nutritional conditions (chow diet, CD) were also used. LD enabled the consequences of an insulin infusion on cholesterol gallstone formation to be evaluated. Subcutaneous osmotic pumps were implanted in all the animals and delivered either 3 IU/day of insulin (insulin groups: CDI, SDI, LDI) or saline (control groups: CDC, SDC, LDC). Several parameters bound to lipid metabolism were measured. The plasma cholesterol concentration remained constant in all the insulin treated groups compared to the controls. Phospholipid and triglyceride concentrations decreased in both the plasma and liver in the CDI and SDI groups. A lower SR-BI mass (around 50%) was found in the liver of CDI and SDI hamsters with concomitant higher hydroxy-methyl-glutaryl coenzyme A reductase activity. The LDL-receptor mass and cholesterol 7alpha-hydroxylase activity in the LDI group were both decreased (-47%, -71% respectively). No variations in the cholesterol gallstone incidence were observed. In conclusion, chronic insulin infusion in growing hamsters induced similar effects on cholesterol metabolism in the CD and SD groups but different ones, between diets containing a low (SD) and a high (LD) sucrose proportion. The distribution of triglycerides and phospholipids in the plasma, liver and bile was also affected by the insulin infusion.
Assuntos
Ácidos e Sais Biliares/biossíntese , Dieta , Hiperinsulinismo/metabolismo , Insulina/administração & dosagem , Fígado/metabolismo , Receptores de Lipoproteínas/metabolismo , Animais , Bile/metabolismo , Glicemia/análise , Colesterol/sangue , Colesterol/metabolismo , Cricetinae , Fezes , Hiperinsulinismo/sangue , Insulina/sangue , Masculino , MesocricetusRESUMO
A comprehensive study of cholesterol, bile acid, and lipoprotein metabolism was undertaken in two strains of hamster that differed markedly in their response to a sucrose-rich/low fat diet. Under basal conditions, hamsters from the LPN strain differed from Janvier hamsters by a lower cholesterolemia, a higher postprandial insulinemia, a more active cholesterogenesis in both liver [3- to 4-fold higher 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR) activity and mRNA] and small intestine, and a lower hepatic acyl-coenzyme A:cholesterol acyltransferase activity. Cholesterol saturation indices in the gallbladder bile were similar for both strains, but the lipid concentration was 2-fold higher in LPN than in Janvier hamsters. LPN hamsters had a lower capacity to transform cholesterol into bile acids, shown by the smaller fraction of endogenous cholesterol converted into bile acids prior to fecal excretion (0.34 vs. 0.77). In LPN hamsters, the activities of cholesterol 7alpha-hydroxylase (C7OHase) and sterol 27-hydroxylase (S27OHase), the two rate-limiting enzymes of bile acid synthesis, were disproportionably lower (by 2-fold) to that of HMG-CoAR. When fed a sucrose-rich diet, plasma lipids increased, dietary cholesterol absorption improved, hepatic activities of HMG-CoA reductase, C7Ohase, and S27OHase were reduced, and intestinal S27OHase was inhibited in both strains. Despite a similar increase in the biliary hydrophobicity index due to the bile acid enrichment in chenodeoxycholic acid and derivatives, only LPN hamsters had an increased lithogenic index and developed cholesterol gallstones (75% incidence), whereas Janvier hamsters formed pigment gallstones (79% incidence). These studies indicate that LPN hamsters have a genetic predisposition to sucrose-induced cholesterol gallstone formation related to differences in cholesterol and bile acid metabolism.
Assuntos
Ácidos e Sais Biliares/metabolismo , Colelitíase/metabolismo , Colesterol/metabolismo , Lipoproteínas/metabolismo , Sacarose/toxicidade , Animais , Sequência de Bases , Sistema Biliar/metabolismo , Colelitíase/genética , Colesterol/sangue , Cricetinae , Primers do DNA , Vesícula Biliar/metabolismo , Predisposição Genética para Doença , Cinética , Metabolismo dos Lipídeos , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Mesocricetus , Receptores de Lipoproteínas/metabolismo , Especificidade da EspécieRESUMO
Adult male genetically hypercholesterolemic RICO rats were studied 6 and 28 days after streptozotocin (STZ) administration together with untreated RICO controls. The absorption coefficient of dietary cholesterol was determined using dual-isotope blood ratio method. Plasma lipoproteins as well as fecal neutral sterols and bile acids were analysed at both experimental times. Liver lipid parameters were measured and lipoprotein receptors (LDLr, SR-BI and HB2) were assayed by immunodetection. Six days after STZ administration, dietary cholesterol absorption was more efficient (+49%) in treated rats than in controls, and stayed higher (+68%) in the diabetic rats sacrificed at day 28. Fecal neutral sterol elimination decreased soon after STZ administration (by 35% at day 6), due to a higher cholesterol absorption coefficient, then increased to control level at day 28, due to installed diabetes-induced hyperphagia. Comparison of the lipoprotein profiles indicated that the concentration of HDL1. which is typically high in control Rico rats, fell significantly in diabetic rats at both experimental times, whereas that of HDL2 increased only at day 28. In diabetic rats, an early and strong enhancement of the hepatic expression of SR-BI appeared at day 6 (+415%) and persisted at day 28, but at a lesser extent (+85%). The expression of LDLr and HB2 was unchanged at day 6, but was significantly modified at day 28 (+140% for LDLr and -50% for HB2). These data show that streptozotocin-induced diabetes in Rico rats results in modifications of the expression of liver lipoprotein receptors which can contribute to alterations of the lipoprotein profile.
Assuntos
Antibacterianos/farmacologia , Colesterol na Dieta/farmacocinética , Hipercolesterolemia/genética , Absorção Intestinal/efeitos dos fármacos , Lipoproteínas/sangue , Receptores de Lipoproteínas/sangue , Estreptozocina/farmacologia , Animais , Ácidos e Sais Biliares/metabolismo , Glicemia/metabolismo , Western Blotting , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Fezes/química , Hipercolesterolemia/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Esteróis/metabolismoRESUMO
The present study was performed in control and ethinyl estradiol-treated rats in order to determine the mechanisms involved in the catabolism of HDL1 cholesteryl ester. Ligand blottings on liver membranes showed that purified HDL1, containing about 70% apolipoprotein E and 10% apolipoprotein AI, bind to the LDL receptor (130 kDa) and not to HB2 (100 kDa) or SR-BI (82 kDa), candidate HDL receptors. Immunoblots showed that the treatment increased the hepatic level of the LDL receptor five- to ten-fold, strongly decreased that of SRBI and did not change that of HB2. An in vivo kinetic study showed that the turnover of HDL1 cholesteryl ester is more rapid in treated than control rats. The liver participation (60%) in this clearance was not modified by the treatment. Therefore, it can be concluded that the catabolism of HDL1 cholesteryl ester, in control as in treated rats, is essentially ensured by the uptake of entire particles in the hepatocytes via LDL receptors.
Assuntos
Proteínas de Transporte , HDL-Colesterol/metabolismo , Etinilestradiol/farmacologia , Lipoproteínas HDL , Fígado/metabolismo , Proteínas de Ligação a RNA , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Animais , Apolipoproteínas A/metabolismo , Apolipoproteínas E/metabolismo , Membrana Celular/metabolismo , Colesterol/metabolismo , HDL-Colesterol/efeitos dos fármacos , HDL-Colesterol/isolamento & purificação , Cinética , Fígado/efeitos dos fármacos , Masculino , Taxa de Depuração Metabólica , Ratos , Ratos Wistar , Receptores de LDL/metabolismo , Receptores de Lipoproteínas/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismoRESUMO
Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model.
Assuntos
Anticolesterolemiantes/uso terapêutico , Colelitíase/prevenção & controle , Resina de Colestiramina/uso terapêutico , Ciclodextrinas/uso terapêutico , beta-Ciclodextrinas , Animais , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Ácido Quenodesoxicólico/metabolismo , Colestanotriol 26-Mono-Oxigenase , Colesterol/sangue , Colesterol/metabolismo , Ácido Cólico/metabolismo , Cricetinae , Sistema Enzimático do Citocromo P-450/metabolismo , Fezes/química , Vesícula Biliar/metabolismo , Absorção Intestinal/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mesocricetus , Fosfolipídeos/sangue , Fosfolipídeos/metabolismo , Esteroide Hidroxilases/metabolismoRESUMO
PURPOSE: The investigation of the effects of ionizing radiation on hepatic cholesterol metabolism and the concentration and composition of plasma lipoproteins in the male Syrian hamster. MATERIALS AND METHODS: After sublethal whole-body 60Co gamma-irradiation (8 Gy, 1 Gy/min), plasma lipoproteins were separated by density-gradient ultracentrifugation. Activities of hydroxymethylglutarylCoA (HMGCoA) reductase and of cholesterol 7alpha-hydroxylase were measured in hepatic microsomes and the low-density lipoprotein (LDL) receptor mass was determined in hepatic total membranes. Lipid peroxidation in LDL was assessed in vitro as the formation of conjugated dienes at 234 nm. A group of pair-fed animals served as controls as the food intake was markedly decreased with exposure to radiation. RESULTS: Plasma lipid concentrations decreased 2 days post-irradiation and then markedly increased by day 6 post-irradiation; plasma cholesterol was increased by 77% and triglycerides by +207%. LDL accumulated in plasma while high-density lipoprotein (HDL) levels decreased. HDL contained significant amounts of apo SAA, the acute phase apolipoprotein. The activities of hepatic HMGCoA reductase, the rate-limiting enzyme for cholesterol synthesis, increased (+125%, p=0.06); hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, decreased (-85%); and the hepatic LDL receptor mass also decreased (-44%). The susceptibility of LDL to oxidation was also increased when animals were exposed to radiation. CONCLUSIONS: Lipoprotein modifications that appeared following radiation exposure may result from an induced inflammatory state and may further contribute to vascular damage.
Assuntos
Colesterol/metabolismo , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Animais , Peso Corporal/efeitos da radiação , Cricetinae , Ingestão de Alimentos/efeitos da radiação , Raios gama , Hidroximetilglutaril-CoA Redutases/efeitos da radiação , Peroxidação de Lipídeos/efeitos da radiação , Fígado/metabolismo , Masculino , Mesocricetus , Receptores de LDL/efeitos da radiaçãoRESUMO
Male Wistar rats weighing 250 g were exposed to 4 Gy of neutrons/gamma radiation (3.33 Gy of neutrons and 0.66 Gy of gamma rays). After whole-body irradiation, plasma cholesterol and phospholipid levels increased up to 62 and 37%, respectively, at day 4 and then returned to control values 12 days after irradiation. Plasma triglyceride concentrations decreased concomitantly with decreased food intake after irradiation but remained higher than in pair-fed control rats. Plasma lipoproteins were separated by ultracentrifugation on a density gradient (1.006-1.210 g/ml). Four days after irradiation, most of the cholesterol (62% compared to 31% in controls, P < 0.001) is transported by apolipoprotein E-rich high-density lipoproteins. At the same time, plasma levels of apolipoproteins B and E were increased by 28 and 65%, respectively, while those of apolipoproteins AI and AIV were reduced by 21 and 59%, respectively. While in the liver of irradiated rats the apolipoprotein B/E receptor number was not modified, the hydroxymethylglutaryl coenzyme A reductase activity was fivefold higher than in control pair-fed rats. Four days after irradiation, the susceptibility of lipoproteins to peroxidation, as measured by the formation of conjugated dienes in the presence of Cu2+, was markedly increased while plasma vitamin E levels were decreased, demonstrating that irradiation reduces antioxidant stores markedly. These results suggest that such modified lipoproteins could be involved in radiation-induced vascular damage.
Assuntos
Lipídeos/sangue , Lipídeos/efeitos da radiação , Lipoproteínas/biossíntese , Lipoproteínas/efeitos da radiação , Animais , Peso Corporal/efeitos da radiação , Colesterol/sangue , Ingestão de Alimentos/efeitos da radiação , Raios gama , Hidroximetilglutaril-CoA Redutases/metabolismo , Peroxidação de Lipídeos/efeitos da radiação , Fígado/metabolismo , Fígado/efeitos da radiação , Masculino , Nêutrons , Ratos , Ratos Wistar , Receptores de Lipoproteínas/metabolismo , Vitamina E/sangue , Irradiação Corporal TotalRESUMO
The present study was designed to examine the effect of streptozotocin (STZ)-induced diabetes on the plasma lipoprotein profile and hepatic expression of the LDL receptor and HDL binding protein (HB2) in hypercholesterolemic Rico rats. The plasma level of HDL1 (density range 1.040-1.063), which is particularly high in this rat strain, decreased (-25%) 28 d after STZ administration (50 mg/kg). In contrast, the treatment increased (+54%) the plasma concentration of HDL2 (density range 1.063-1.210). These variations in the lipoprotein concentrations were associated with inverse changes in the hepatic protein levels of the LDL receptor (+118%) and HB2 (-46%). These results suggest that the hepatic expression of HB2, a putative HDL receptor, can influence the plasma level of apo Al-rich HDL as has already been shown for the LDL receptor for apo B/E containing lipoproteins.
Assuntos
Proteínas de Transporte , Diabetes Mellitus Experimental/metabolismo , Hipercolesterolemia/metabolismo , Insulina/deficiência , Lipoproteínas HDL , Lipoproteínas/metabolismo , Fígado/metabolismo , Proteínas de Ligação a RNA , Receptores de Lipoproteínas/metabolismo , Animais , Apolipoproteínas/metabolismo , Peso Corporal , Diabetes Mellitus Experimental/complicações , Hipercolesterolemia/complicações , Hipercolesterolemia/genética , Intestinos/patologia , Fígado/patologia , Tamanho do Órgão , Ratos , Ratos Mutantes , Receptores de LDL/metabolismo , EstreptozocinaRESUMO
Since experimental Se deficiency results in a significant increase in plasma cholesterol concentration the present investigation was undertaken to assess further the influence of this deficiency on the expression of proteins involved in hepatic lipid metabolism. Se deficiency was induced by feeding weanling male Wistar rats on a deficient diet for 6 weeks. Hypercholesterolaemia associated with Se deficiency was related to increased 3-hydroxy-3-methylglutaryl-coA (HMG-CoA) reductase (EC 1.1.1.34) activity in liver microsomes as compared with control animals. Hepatic lipoprotein receptor levels (LDL-receptor and HDL-binding proteins, HB1 and HB2) were not significantly affected by Se deficiency, as assessed by immunoblotting. Plasma triacylglycerol concentrations tended to decrease in Se-deficient rats in concert with their reduced post-Triton secretion. There was no significant effect of Se deficiency on the hepatic synthesis of apolipoproteins. These results point to the need for further investigations into the mechanism related to the increased activity of HMG-CoA reductase and the enhanced cholesterogenesis in the liver of Se-deficient rats likely to result from this.
Assuntos
Metabolismo dos Lipídeos , Fígado/metabolismo , Selênio/deficiência , Animais , Hidroximetilglutaril-CoA Redutases/metabolismo , Lipoproteínas/metabolismo , Masculino , Microssomos Hepáticos/enzimologia , Ratos , Ratos Wistar , Triglicerídeos/sangue , DesmameRESUMO
BACKGROUND/METHODS: In this study, pigs fed for 3 weeks a well-balanced semi-purified diet enriched with 0.3% cholesterol and 0, 5 or 10% beta-cyclodextrin were proposed as new animal donors of gallbladder bile exhibiting different rates of cholesterol crystallization, in order to gain insight into the early mechanisms underlying cholesterol precipitation in vivo. The appearance and growth of cholesterol crystals were monitored in the incubated freshly collected gallbladder biles through light microscopy and concomitant time-sequential determination of crystallized cholesterol concentration, and interpreted in terms of the composition of the bile. RESULTS: Although the concentration of total lipids and proteins and the relative proportions of bile acids, phospholipids, and cholesterol remained unchanged under beta-cyclodextrin, the cholesterol crystallization increased in the following order: 0<<10<5% beta-cyclodextrin. Concomitantly, the proportion of chenodeoxycholic acid in bile, and the hydrophobicity index of the biliary bile acid mixture increased in the following order: 0<5<10% beta-cyclodextrin (the same as reported elsewhere for the decrease in the antinucleating ApoA1), while sn-2 arachidonoyl biliary lecithins were specifically increased with 5% beta-cyclodextrin in the diet. CONCLUSIONS: We hypothesized that lecithin molecular species may be the determinant factor in modulating high cholesterol crystallization rates in biles otherwise enriched with hydrophobic bile acids.
Assuntos
Bile/química , Colesterol na Dieta/administração & dosagem , Colesterol/química , Ciclodextrinas/administração & dosagem , Aditivos Alimentares/administração & dosagem , beta-Ciclodextrinas , Animais , Bile/efeitos dos fármacos , Ácidos e Sais Biliares/análise , Precipitação Química , Cristalização , Ciclodextrinas/análise , Fezes/química , Seguimentos , Lipídeos/análise , Masculino , Fosfatidilcolinas/análise , SuínosRESUMO
To examine the effects of beta-cyclodextrin (BCD), a non-absorbable carbohydrate, on lipid metabolism, growing pigs were fed a 0.3% cholesterol-enriched diet for 4 weeks or this diet containing 5% or 10% BCD. Pigs fed a basal diet without added cholesterol or BCD were used as controls. The cholesterol-rich diet induced hypercholesterolemia (1.75 vs. 0.84 g/l plasma) due to increased LDL concentration, delayed the plasma clearance of vitamin A, enhanced liver cholesterol storage, lowered the hepatic activities of LDL-receptors (by 47%) and HMG-CoA reductase (by 62%), stimulated cholesterol 7alpha-hydroxylase (x3), and accelerated the fecal output of neutral sterols (x4). Addition of BCD to the cholesterol-rich diet prevented the elevation of plasma cholesterol due to dietary cholesterol excess. Moreover, BCD produced a dose-dependent effect in reducing liver cholesterol storage, stimulating hepatic cholesterogenesis, increasing the proportion of primary bile acids in bile and in feces, and the fecal loss of neutral sterols and bile acids. Pigs receiving 10% BCD thus differed markedly from controls, especially for HMG-CoA reductase and cholesterol 7alpha-hydroxylase hepatic activities (x5), and fecal output of total bile acids (x3) and hyocholic acid (x20), and their overall cholesterol synthesis was higher (+50%), despite the abundant dietary cholesterol. Owing to the property of BCD to bind cholesterol and bile acids in vitro, these results suggest that this resistant carbohydrate accelerates body cholesterol turnover by reducing cholesterol absorption, increasing cholesterol and bile acid synthesis, and altering the action of the intestinal microflora.
Assuntos
Anticolesterolemiantes/farmacologia , Colesterol na Dieta/farmacologia , Colesterol/metabolismo , Ciclodextrinas/farmacologia , beta-Ciclodextrinas , Animais , Bile/metabolismo , Ácidos e Sais Biliares/análise , Colesterol na Dieta/metabolismo , Jejum/sangue , Fezes/química , Insulina/sangue , Lipídeos/sangue , Fígado/metabolismo , Masculino , Período Pós-Prandial , Esteroides/análise , SuínosRESUMO
The present study was designed to examine apolipoprotein and LDL receptor gene expression in genetically hypercholesterolemic RICO rats. In the plasma of RICO rats as compared to SW (control) rats, the hypercholesterolemia (+41%) was associated with a significant increase in plasma apo B (+23%) and apo E (+68%) concentrations. Study of apolipoprotein synthesis in the liver has shown that this increase in plasma apo B and apo E concentrations was not associated with modification in their synthesis and mRNA levels. Study of apo E mRNA level in various tissues has shown only the modification in adrenals in RICO as compared to SW rats (2.7-fold increase). Study of LDL binding, LDL receptor mass and LDL receptor mRNA level in the liver of RICO and SW rats has shown no significant differences between these two strains. EDTA-resistant binding of rat LDL was lower in RICO than in SW rats suggesting that binding sites others than the LDL receptor are present in lesser amount in this hypercholesterolemic strain.
Assuntos
Apolipoproteínas/metabolismo , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Receptores de LDL/metabolismo , Glândulas Suprarrenais/metabolismo , Animais , Apolipoproteínas/genética , Modelos Animais de Doenças , Expressão Gênica , Hipercolesterolemia/genética , Masculino , RNA Mensageiro/análise , Ratos , Receptores de LDL/genéticaRESUMO
The effects of hyodeoxycholic (HDCA) and alpha-hyocholic acids (alpha-HCA), on cholesterol, bile acid and lipoprotein metabolism, were studied in hamsters. The animals were fed a low cholesterol control diet supplemented with 0.1% HDCA or alpha-HCA for 3 weeks. In both treated groups, the LDL-cholesterol concentration was significantly lowered and was associated with a global hypocholesterolemic effect. Moreover, hepatic cholesterol ester storage was reduced and HMGCoA reductase activity was respectively enhanced 13.5-times and 7.7-times in HDCA and alpha-HCA groups compared to controls. In contrast, cholesterol 7 alpha-hydroxylase activity and LDL-receptor activity and mass were not modified. In bile, the cholesterol saturation index was increased 5-fold (HDCA group) and 2-fold (alpha-HCA group) as a consequence of an enlarged proportion of biliary cholesterol. The two 6-hydroxylated bile acids induced an enhanced fecal excretion of neutral sterols (HDCA group: 11.6-times, alpha-HCA group: 3.2-times versus controls) which was consistent with a 59% decrease in intestinal cholesterol absorption in the HDCA group. The major effects due to bile acid treatments were a decrease in LDL-cholesterol concentration, a strong stimulation of hepatic cholesterol biosynthesis and an excessive loss of cholesterol in feces. These perturbations might be the result of the enrichment of bile with hydrophilic bile acids, leading to a limited return of endogenous cholesterol from the intestine to the liver.
Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Ácidos Cólicos/administração & dosagem , Ácido Desoxicólico/administração & dosagem , Animais , Bile/metabolismo , Cricetinae , Dieta , Absorção Intestinal , Lipoproteínas/metabolismo , Fígado/metabolismo , Mesocricetus , Receptores de LDL/análiseRESUMO
Male and female rats fed a cystine-rich diet (5% L-cystine) became hypercholesterolemic after 2 months, with 2-fold higher cholesterol levels carried mainly by the HDL1 and HDL2 lipoprotein fractions. Post-heparin lipoprotein lipase activity was increased in male rats only (60%, P < 0.01), while hepatic lipase (HL) activity was increased in both males and females (48%, P < 0.001 and 27%, P < 0.01, respectively). In the liver, HL activity and mRNA levels were increased in males (30%, P < 0.01, and 70%, P < 0.001, respectively), but not in females. A higher correlation between HDL1-cholesterol and liver HL activity was found in male rats than in female rats. In the latter, although the cystine diet induced a virtually identical increase in HDL1-cholesterol, HL gene expression was not promoted. It is suggested that HL gene expression may be triggered by the uptake of HDL1-cholesterol in male rats, while oestrogens in female rats would counteract this effect.
Assuntos
Cistina/farmacologia , Hipercolesterolemia/enzimologia , Lipase/metabolismo , Fígado/enzimologia , Animais , HDL-Colesterol/metabolismo , Dieta , Feminino , Expressão Gênica/efeitos dos fármacos , Lipase/genética , Masculino , RNA Mensageiro/análise , Ratos , Ratos Wistar , Fatores Sexuais , Regulação para CimaRESUMO
This study examined the effects of diet-induced hypercholesterolemia on plasma apolipoprotein (apo) concentrations and hepatic apolipoprotein mRNA levels in rats. Hypercholesterolemia was induced by feeding rats diets containing an excess of either cholesterol or cystine. After cholesterol feeding, plasma apo E and apo B concentrations were lower (-65%, P < 0.001) and greater (+39%, P < 0.01), respectively, compared with control diet-fed rats. After cystine feeding, plasma apo B and apo E concentrations were greater (+46%, P < 0.01 and +75%, P < 0.001, respectively) and plasma apo A-IV concentration was lower (-29%, P < 0.001) than in rats fed control diet. After cholesterol or cystine feeding, a tendency (one-way ANOVA, P = 0.08) for greater apo B mRNA level (+42% and +47%, respectively) was observed compared with control diet-fed rats. No difference emerged between groups for apo E and apo A-I mRNA levels. An opposite effect of cholesterol and cystine feeding was shown for apo A-IV mRNA level, i.e., higher after cholesterol feeding (+47%, P < 0.05) and lower after cystine feeding (-65%, P < 0.01). From this work, it seems that hypercholesterolemia induced by dietary cholesterol or by increased cholesterogenesis in cystine-fed rats is characterized by different plasma lipoprotein and apolipoprotein concentrations and is associated with different apolipoprotein gene expression in the liver.
Assuntos
Apolipoproteínas/análise , Colesterol na Dieta/administração & dosagem , Cistina/administração & dosagem , Hipercolesterolemia/metabolismo , Lipoproteínas/sangue , Actinas/análise , Actinas/genética , Animais , Apolipoproteínas/sangue , Apolipoproteínas/genética , Apolipoproteínas E/sangue , Colesterol/análise , Colesterol/sangue , Colesterol na Dieta/efeitos adversos , Cistina/efeitos adversos , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Fígado/química , Fígado/enzimologia , Masculino , RNA Mensageiro/análise , Distribuição Aleatória , Ratos , Ratos Wistar , Triglicerídeos/análise , Triglicerídeos/sangueRESUMO
The effects of a fish oil concentrate on blood lipids and lipoproteins were examined in relation to their effects on liver fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, adipose tissue lipoprotein lipase (LPL), and hepatic triglyceride lipase (H-TGL). For 15 days, 2-mo-old rats were fed a control diet (10% of calories from fat, 4% fat by weight) or diets with 50% of calories (25% wt/wt) provided by lard, lard and fish oil calories (35%/15%), or lard and corn oil (35%/15%). The high-lard diet increased plasma chylomicron and liver triglycerides. The high-lard diet greatly decreased FAS, HMG-CoA reductase, and LPL activities; it also reduced H-TGL activity. Compared with the lard diet, the lard-fish oil diet decreased plasma TG by drastically lowering chylomicron (4-fold, P < 0.001) and very-low-density lipoprotein levels (P < 0.001). It also reduced high-density lipoprotein levels. The lard-fish oil diet prevented hepatic triglyceride accumulation and decreased FAS activity and mass by 3.5-fold (P < 0.001) but did not further decrease HMG-CoA reductase activity. Adipose tissue LPL activity was 2.5-fold (P < 0.001) higher with the lard-fish oil diet than with the lard diet, and H-TGL activity decreased significantly (-32%, P < 0.01), despite unaltered levels of H-TGL mRNA. These effects were significant with only 10% fish oil concentrate in the lard diet. They were not observed with the lard-corn oil diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Gorduras na Dieta/farmacologia , Ácido Graxo Sintases/metabolismo , Óleos de Peixe/farmacologia , Lipólise , Lipoproteínas/sangue , Fígado/enzimologia , Animais , Epididimo/enzimologia , Hidroximetilglutaril-CoA Redutases/metabolismo , Lipase/genética , Lipídeos/sangue , Lipase Lipoproteica/metabolismo , Masculino , RNA Mensageiro/análise , Ratos , Ratos WistarRESUMO
Copper deficiency induces hypercholesterolemia in the rat. This hypercholesterolemia is mainly due to an increase in apo E-rich high density lipoproteins (HDL1). The present study was undertaken to determine whether the HDL increase could be explained by altered low-molecular weight apolipoprotein (apo) synthesis in the liver. The effect of copper deficiency on apo A-I, apo A-IV and apo E concentrations in plasma, as well as on respective mRNA levels and synthesis in the liver, were therefore investigated. We observed that the increased HDL1 levels in the plasma of copper-deficient rats were associated with a significant rise in plasma apo E concentrations; however, plasma apo A-I and apo A-IV concentrations remained unchanged. Liver apo synthesis and respective apo mRNA levels were not significantly altered in copper-deficient animals when compared to control rats. No changes in apo E mRNA levels in various tissues from copper-deficient, as compared to control rats, were noted. Based on the data obtained, it was concluded that the observed changes in plasma lipoprotein and apo concentrations are not related to changes in low-molecular weight apo synthesis in the liver. The mechanisms of the impaired catabolism of HDL1 should be further evaluated to possibly explain the observed increase in this fraction in copper-deficient rats.
Assuntos
Apolipoproteína A-I/biossíntese , Apolipoproteínas A/biossíntese , Apolipoproteínas E/biossíntese , Cobre/deficiência , Fígado/metabolismo , Animais , Apolipoproteína A-I/sangue , Apolipoproteínas A/sangue , Apolipoproteínas E/sangue , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , DesmameRESUMO
The effects of long-term treatment with simvastatin on plasma lipoproteins, plasma apolipoproteins, and on hepatic apolipoprotein gene expression were evaluated in genetically hypercholesterolemic (RICO) rats. Simvastatin administration caused a decrease in plasma triglyceride and phospholipid concentrations. Plasma cholesterol concentration was not changed by simvastatin, but cholesterol distribution among plasma lipoproteins was altered. Plasma apo B, apo A-I, and apo A-IV concentrations were lowered by simvastatin treatment whereas plasma apo E concentration was not affected by this drug. In the liver, simvastatin treatment induced a significant decrease of apo E mRNA level but had no effect on apo B, apo A-I, and apo A-IV mRNA abundances. It appears that simvastatin may modify plasma apolipoprotein concentrations by influencing their hepatic synthesis at both pre- and posttranscriptional levels.
Assuntos
Apoproteínas/sangue , Apoproteínas/genética , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Hipolipemiantes/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lovastatina/análogos & derivados , RNA Mensageiro/metabolismo , Animais , Apolipoproteínas E/genética , Expressão Gênica/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia/metabolismo , Lipoproteínas/sangue , Fígado/fisiologia , Lovastatina/farmacologia , Masculino , Fosfolipídeos/sangue , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos , Sinvastatina , Fatores de Tempo , Triglicerídeos/sangueRESUMO
The present study was designed to examine if induction of apolipoprotein B synthesis is associated with hypercholesterolemia in copper-deficient rats. This hypercholesterolemia mainly resides in an increase in the HDL-1 and LDL and is associated with a significant increase in plasma apoB concentration. Liver apoB mRNA levels were not significantly modified in deficient animals as compared to control rats. Studies on liver apolipoprotein synthesis indicated that apoB100 synthesis was increased in deficient animals whereas apoB48 synthesis was unchanged. Thus, it appears that the increase in apoB synthesis in the liver of copper-deficient rats occurs at the posttranscriptional level. The selective increase in apoB100 synthesis indicates the possible impact of this deficiency on the editing of apoB. An increase in apoB100 synthesis by the liver in copper-deficient rats may significantly contribute to the increase in plasma concentration of LDL.