Hepatic acyl-CoA Oxidase Activity Research Articles

Effects of lipid-lowering pharmaceutical clofibrate on lipid and lipoprotein metabolism of grass carp (Ctenopharyngodon idellal Val.) fed with the high non-protein energy diets

This study investigated the effects of clofibrate treatment on blood lipids, hepatic enzyme activities and relative expression of genes involved in lipid metabolism of grass carp fed with high non-protein energy diets. For that purpose, five diets were formulated: a commercial-like diet (Control), a high-carbohydrate diet (HC), a high-fat diet (HF) and two diets identical to the HC and HF diets, but supplemented with 1.25 g kg(-1) clofibrate (HC + Clo and HF + Clo diets). Grass carp fed the HC and HF diet exhibited increases in blood lipids and body fat compared with the control group after 4 weeks. In the clofibrate treatment groups, there was a marked decrease in triacylglycerol and cholesterol concentrations of plasma, and total lipids of the whole body, mesentery adipose tissue and liver tissue. Fish treated with clofibrate exhibited increased hepatic acyl-CoA oxidase activity, but did not show any changes in carnitine palmitoyltransferase (CPT) I activity compared with HC and HF diets without clofibrate. Clofibrate treatment had no effect on peroxisome proliferator-activated receptor alpha and CPT I mRNA expression. However, there was an increase in lipoprotein lipase expression in the clofibrate-treated groups. In addition, the relative mRNA expression levels of hepatic de novo lipogenic enzymes (fatty acid synthetase and acetyl coenzyme-A carboxylase) were significantly higher in the fish fed the HC diet than those of other groups, and clofibrate inhibited this increase. These results suggest that clofibrate has the hypolipidaemic effects and affects lipid metabolism in grass carp.

Short-term oral toxicity of three biodiesels and an ultra-low sulfur diesel in male rats

Male rats were administered one of three biodiesels – soy oil methyl ester (SoME-2), canola oil methyl ester (CaME-2), and methyl ester of animal frying oil (FrAME-1) at 5, 50 and 500 mg/kg, or ultra-low sulphur diesel (ULSD) at 500 mg/kg. Control was administered the vehicle (corn oil) only. After 4-week treatment, serum methanol and formic acid were unchanged or minimally elevated in all treatment groups. Mild histopathological changes in the liver were observed in animals receiving 500 mg/kg biodiesels and ULSD but hepatomegaly, increased phase I and II drug-metabolizing enzyme activities and urinary ascorbic acid were found only in the ULSD group. The ULSD group had increased kidney weight, changes in kidney histopathology, and increased urinary albumin and N-acetylgluocosaminidase activity. Biodiesels and ULSD caused increase in hepatic acyl-CoA oxidase activity. ULSD and FrAME-1 caused decrease in serum free fatty acid while CaME-2 caused decreases in both serum triglycerides and free fatty acids. FrAME-1 produced an increase in liver protein carbonyls and ULSD caused increased liver glutathione. The results indicated that ULSD caused more histopathological and biochemical effects than biodiesels. Biodiesels produced lipid effects and oxidative stress that were feedstock-dependent. The mechanisms and significance of increased hepatic acyl-CoA oxidase activity required further study.

Thia fatty acids with the sulfur atom in even or odd positions have opposite effects on fatty acid catabolism

As tools for mechanistic studies on lipid metabolism, with the long-term goal of developing a drug for the treatment of lipid disorders, thia FA with the sulfur atom inserted at positions 3-9 from the carboxyl group were fed to male Wistar rats for 1 wk to determine their impact on key parameters in lipid metabolism and hepatic levels of thia FA metabolites. Thia FA with the sulfur atom in even positions decreased hepatic and cardiac mitochondrial beta-oxidation and profoundly increased hepatic and cardiac TAG levels. The plasma TAG level was unchanged and the hepatic acyl-CoA oxidase activity increased. In contrast, thia FA with the sulfur atom in odd positions, especially 3-thia FA, tended to increase hepatic and cardiac FA oxidation and acyl-CoA oxidase and carnitine palmitoyltransferase-II activities, and decreased the plasma TAG levels. The effects seem to be related to differences in the catabolic rate of the thia FA. Differences between the two groups of acids were also observed with respect to the regulation of genes involved in FA transport and catabolism. Feeding experiments with 3- and 4-thia FA in combination indicated that the 4-thia FA partly attenuated the effects of the 3-thia FA on mitochondrial FA oxidation and the hepatic TAG level. In summary, the position of the sulfur atom in the alkyl chain, especially whether it is placed in the even or odd position, is crucial for the biological effect of the thia FA.

Effects of fenofibrate and insulin on the biosynthesis of unsaturated fatty acids in streptozotocin diabetic rats

Both insulin and PPAR- α up-modulate hepatic Δ9, Δ6 and Δ5 desaturating enzymes involved in the biosynthesis of mono- and polyunsaturated fatty acids. Currently, we have examined for 9 days the independent and simultaneous effects of daily glargine insulin and fenofibrate administration on the insulinemia, glycemia, hepatic acyl-CoA oxidase activity and mRNAs and enzymatic activities of stearoyl-CoA desaturase-1 (SCD-1) and Δ5 desaturase in streptozotocin diabetic rats. Glargine insulin depressed the hyperglycemia of diabetic rats at 4 h, but not after 24 h of injection. Fenofibrate increased the radioimmunoreactive insulinemia in non-diabetic rats without changing the glycemia. Insulin increased the mRNAs and activities of SCD-1 and Δ5 desaturase depressed in diabetic rats. Fenofibrate increased acyl-CoA oxidase activity, and the mRNAs and activities of both desaturating enzymes in non-diabetic, diabetic and insulin-treated diabetic rats, but was less effective in the mRNAs modification of diabetic animals. Therefore, insulin, and fenofibrate through PPAR- α activation, enhance liver mRNAs and activities of SCD-1 and Δ5 desaturases independently and synergistically through different mechanisms. Insulin and fenofibrate independently increased the 18:1/18:0 ratio in liver lipids, increasing the fluidity of the membranes. The 20:4/18:2 ratio was maintained. Fenofibrate increased palmitic acid, but decreased stearic acid percentage in liver lipids.

Dietary Curcuminoids Prevent High-Fat Diet–Induced Lipid Accumulation in Rat Liver and Epididymal Adipose Tissue

Curcumin and its structurally related compounds (curcuminoids), the phenolic yellowish pigments of turmeric, display antioxidative, anticarcinogenic and hypocholesterolemic activities. In this study, we investigated the effects of dietary supplemented curcuminoids [commercial grade curcumin: a mixture of curcumin (73.4%), demethoxycurcumin (16.1%) and bisdemethoxycurcumin (10.5%)] on lipid metabolism in rats. Male Sprague-Dawley rats were assigned to three diet groups (n = 6) and fed a moderately high-fat diet (15 g soybean oil/100 g diet) for 2 wk. One diet group did not receive supplements (CONT), while the others were supplemented with 0.2 g curcuminoids/100 g diet (CUR0.2) or 1.0 g curcuminoids/100 g diet (CUR1.0). Liver triacylglycerol and cholesterol concentrations were significantly lower in CUR1.0 rats than in CONT rats. Plasma triacylglycerols in the VLDL fraction were also lower in CUR1.0 rats than in CONT rats (P < 0.05). Hepatic acyl-CoA oxidase activity of both the CUR0.2 and CUR1.0 rats was significantly higher than that of CONT rats. Furthermore, epididymal adipose tissue weight was significantly reduced with curcuminoid intake in a dose-dependent manner. These results indicate that dietary curcuminoids have lipid-lowering potency in vivo, probably due to alterations in fatty acid metabolism.

Mitogenic effect of retinoid X receptor agonists in rat liver

(E)-2-[2-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)propen-l-yl]-4-thiophenecar-boxylic acid (AGN 191701) and other retinoid X receptor (RXR)-selective agonists were observed to cause Hepatomegaly in rats. The purpose of the present study was to understand the biochemical basis of RXR agonist-induced hepatomegaly. Male Fischer rats were implanted s.c. with osmotic pumps containing 5-bromo-2′-deoxyuridine (BrdU) and treated by gavage with 0, 60, or 180 μmol/kg/day of AGN 191701 for 3 days. AGN 191701 caused dose-dependent hepatomegaly in the absence of hepatic necrosis and increased hepatocyte BrdU labeling index (LI). To determine if AGN 191701-induced hepatic hyperplasia was sustained, rats were treated by gavage with 60 μmol/kg of AGN 191701 for up to 7 days and exposed to BrdU via osmotic pump on days 1–3 or on days 6–8. Hepatocyte LI and mitotic index were increased only in rats exposed to BrdU on days 1–3, indicating that AGN 191701-induced hepatocyte proliferation was transient. The receptor specificity of this mitogenic effect was tested by co-treating rats for 2 days with various retinoids and BrdU. 2-(5,6,7,8-Tetrahydro-5,5,8, 8-tetramethyl-2-naphthyl)-2-(4-carboxylphenyl)-l,3-dioxolane (SR11237), an RXR-selective agonist, and (E)-5-[2-(5,6,7,8-tetrahydro-3,5,5,8-pentamethyl-2-naphthyl)propen-l-yl]-2-thiophenecarboxylic acid (AGN 191659), a retinoic acid receptor (RAR)/RXR pan-agonist, both increased hepatocyte LI. Two RAR-selective agonists, all- trans-retinoic acid and (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propen-l-yl] benzoic acid (TTNPB), did not affect hepatocyte LI. To determine if RXR agonists have biochemical effects in common with a peroxisome proliferator, various endpoints were measured 24 hr after two daily treatments with AGN 191701, SR11237, or clofibrate. While all three compounds induced hepatic acyl CoA oxidase activity, only clofibrate increased hepatic carnitine acyl transferase activity and lowered serum triglycerides. Taken together, these data show that RXR-selective agonists but not RAR-selective agonists cause hepatomegaly accompanied by hepatocyte mitogenesis in rats. The fact that RXR agonists have some biological effects distinct from RAR agonists and clofibrate suggests that RXR-selective agonists may have unique therapeutic applications.

Effects of joint exposures to selected peroxisome proliferators on hepatic acyl-CoA oxidase activity in male B6C3F1 mice.

The interaction potential of peroxisome proliferators of similar and dissimilar structure was examined in B6C3F1 mice. Mice were fed diets containing varying concentrations of ciprofibrate (Cipro), clofibrate (Clof) or di(2-ethylhexyl)phthalate (DEHP), or combinations of Cipro and Clof or Cipro and DEHP for 4 d. Induction of peroxisomal beta-oxidation, measured by increased acyl-CoA oxidase activity, was used as the endpoint for analysis. An additive response occurred following joint exposure to the structurally related compounds Cipro and Clof, whereas a possible synergistic response occurred at low dose combinations of the structurally dissimilar Cipro and DEHP. These findings represent the first report assessing the in-vivo interaction potential of structurally similar and dissimilar peroxisome proliferators and provides insight into the dose-response nature of joint exposures to certain non-genotoxic carcinogens.

Different regulation of hepatic peroxisomal β-oxidation activity in rats treated with clofibrate and partially hydrogenated marine oil

Total RNAs from the livers of rats treated with clofibrate and partially hydrogenated marine oil (PHMO) wer translated in a reticulocyte-lysate cell-free protein-synthesizing system. In clofibrate-treated rats, mRNA activity for acyl-CoA oxidase (AO), the rate-limiting enzyme of the peroxisomal β-oxidation system, was increased markedly compared with the control, whereas the increase was less than 2-fold in PHMO-treated rats. When rats were treated with both clofibrate and PHMO in vivo , an additional increase in the hepatic AO activity was observed compared with either treatment alone, suggesting that increases in the activities of peroxisomal β-oxidation in the rats treated with clofibrate and PHMO are based on two distinct mechanisms.