Effect of p-chlorophenoxyisobutyrate (CPIB) fed to rats on hepatic biosynthesis and catabolism of ubiquinone

The effect of p-chlorophenoxyisobutyrate (CPIB) feeding on cholesterol and ubiquinone metabolism in rats was investigated. The results obtained from acetate-1-(14)C and mevalonate-2-(14)C incorporation studies both in vivo and in vitro confirm the results of other workers that CPIB feeding caused a metabolic block in the conversion of acetate to mevalonate, thereby inhibiting over-all steroidogenesis. Liver ubiquinone synthesis was inhibited in CPIB-fed rats, but a block in the catabolism of the ubiquinone resulted in accumulation of ubiquinone in CPIB-fed animals.     

Nephrotoxic activity in rats fed diets containing DL-3-(N-phenylethylamino)-alanine

Rats were fed DL-3-(N-phenylethalamino)-alanine which resulted in kidney lesions histologically identical with those produced by the structurally related compound lysinoalanine. Possible mechanisms for nephrotoxicity are discussed.     

Hepatic fatty acid-supported respiration in rats fed an energy-dense diet

The energy balance and hepatic fatty acid-supported respiration were studied in rats fed a control or an energy-dense diet. In addition, state 3 and 4 respiratory rates as well as ketone body production with palmitoylcarnitine as substrate were determined in isolated mitochondria. Metabolizable energy intake and energy expenditure increased in rats fed an energy-dense diet, but the gain in body weight and lipid content remained unchanged. No variation occurred in the mitochondrial palmitoylcarnitine utilization rate and ketone body production, but a significant increase in the mitochondrial content of ketone bodies and the serum levels was found in rats fed an energy-dense diet. Furthermore, we have shown a significant increase in fatty acid-stimulated respiration in hepatocytes from rats fed an energy-dense diet. The enhanced hepatic fatty acid utilization as an energy substrate found in rats fed an energy-dense diet may contribute to reduce the availability of lipids for storage, thus counteracting the development of obesity.     

Brown adipose tissue activity in hypocaloric-diet fed lactating rats

Hypocaloric diet feeding reduced the mitochondrial protein content and whole tissue GDP-binding in interscapular brown adipose tissue from both virgin and lactating rats. A reduction in brown fat lipoprotein lipase activity was also detected in underfed virgin and lactating animals. These results indicate that lactation in the rat, even though it produces a reduction in brown fat activity, does not impair the capacity of the tissue to respond to a diminished caloric intake by lowering its activity further.     

Hepatic collagenolytic activity in rats after carbon tetrachloride poisoning

1. Collagenolytic activity towards acid-soluble collagen labelled with [(14)C]-proline was assayed in rat liver with and without carbon tetrachloride poisoning. The products of enzymic digestion were found to be free amino acids and peptides. 2. The hepatic collagenolytic activity increased under conditions of single-dose and subacute carbon tetrachloride poisoning, and correlated with hydroxyproline content. The highest activity was found during recovery from subacute poisoning. 3. Under the same experimental conditions, hepatic acid-proteinase activity changed independently of the collagenolytic activity and also of hepatic hydroxyproline content. 4. The increased collagenolytic activity during carbon tetrachloride poisoning was found mainly in the supernatant fraction. 5. The ratio of the collagenolytic activity to hepatic hydroxyproline content increased during recovery from single-dose and subacute poisoning, and decreased during subacute poisoning.     

Hepatic phosphatidylinositol kinase activity in continuously endotoxemic rats.

The activity of phosphatidylinositol (PI) kinase and the content and fatty acid composition of inositol phospholipids (IPLs) were analyzed in the livers of rats that had been continuously infused with Escherichia coli endotoxin (ET) or saline for 30 h. Maximal enzymatic activity in total liver membrane fractions was observed in the presence of 1 mM ATP, 20 mM MgCl2, exogenously added 0.3 mM PI and Triton X-100 (0.25%). The activity of PI kinase for endogenous and exogenous PI was 43 and 79% higher respectively, in ET- as compared with saline-infused rats. The Km of the enzyme for ATP was not altered (0.175 mM), while the apparent Vmax was higher for ET- as compared with saline-infused rats (0.48 and 0.38 nmol of phosphatidylinositol 4-phosphate formed/mg protein per min, respectively). The ET-induced higher activity of PI kinase was paralleled by a 68-78% increase in the content of polyphosphoinositides (PPI), while PI content was unchanged. All IPLs from livers of endotoxemic rats had a lower content of arachidonic acid. We demonstrate for the first time that ET can directly and/or indirectly stimulate the net synthesis of PPI in liver cells. This effect could serve to modulate the PPI derived signals by increasing the availability of the substrate phosphatidylinositol 4,5-bisphosphate.     

Covariance of tricarboxylate carrier activity and lipogenesis in liver of polyunsaturated fatty acid (n-6) fed rats.

The mitochondrial tricarboxylate (citrate) carrier plays an important role in hepatic intermediary metabolism because, among other functions, it supplies the cytosol with acetyl units for fatty-acid synthesis. In this study, the effect of polyunsaturated fatty acids (PUFA, n-6) on the function of this mitochondrial transporter and on lipogenic enzyme activities was investigated by feeding rats for 4 weeks with a 15%-fat diet composed of high linoleic safflower oil. Citrate transport was strongly reduced in liver mitochondria isolated from PUFA-treated rats. A reduced transport activity was also observed when solubilized mitochondrial citrate carrier from PUFA-treated rats was reconstituted into liposomes. In the same animals, a decrease of cytosolic lipogenic enzyme activities was observed. These results indicate a coordinated modulation of citrate carrier and of lipogenic enzyme activities by PUFA feeding. Kinetic analysis of the carrier activity showed that only V(max) decreased, whereas K(m) was almost virtually unaffected. The PUFA-mediated effect is most likely due to the reduced mRNA level and lower content of the citrate carrier protein observed in the safflower oil-fed rats.     

Hepatic uptake of chylomicrons and triglyceride emulsions in rats fed diets of differing fat content

The hepatic removal of plasma chylomicrons was determined for rats fed the following diets: a) containing no triglyceride, b) regular chow diet with 4.5% of its mass as lipid and, c) a corn oil-supplemented chow with triglyceride accounting for 20% of the mass. The fractional hepatic uptake of either radiolabeled chylomicrons or a triglyceride emulsion was reciprocally related to the amount of lipid in the diet. The animals receiving only carbohydrate and protein calories had the most active hepatic uptake of particulate triglyceride and were observed to have a significant decrease in the plasma concentration of the C apolipoproteins. The addition of either C-I, C-II, or C-III apoproteins to the triglyceride emulsion prior to intravenous injection produced a significantly lower hepatic triglyceride recovery of emulsions containing apoC-III. When the plasma of animals fed a fat-free diet was supplemented with human C-III-1 apolipoprotein, the distribution into the liver of either enterally administered fatty acid or parenteral triglyceride was diminished. The triglyceride content in the liver of the rats fed fat-free or corn oil-supplemented diets was significantly greater than that of the control rats and composition was somewhat similar to that of lymph triglyceride. The studies indicate an important influence of dietary lipid on both the partition of plasma triglyceride into the liver and the steady state hepatic triglyceride content.