Physiological mechanism by which acetyl CoA carboxylase is regulated

Summary Compared with rats fed a normal diet, the activity of the protein inhibitor of acetyl CoA carboxylase in rat liver doubled after 48 h of fasting. Conversely, acetyl CoA carboxylase activity was diminished by nearly one half. In animals fasted and then subsequently refed a fat free diet, acetyl CoA carboxylase activity was elevated by nearly 9-fold, with a concomitant decrease in the activity of the protein inhibitor by about 9-fold as compared to fasted rats. Hence it appears that the regulatory protein inhibitor for acetyl CoA carboxylase is of physiological significance for fatty acid biosynthesis.This work supported by grants AM 01383 and AM 21148 from the National Institute of Artheritis, Metabolic and Digestive Disease. We thank Dr J. Porter for his support.     

Effect of starvation on enzymes related to lipid metabolism in guinea-pig lungs

The changes in activities of acetyl CoA carboxylase, microsomal fatty acid elongation enzyme, choline phosphotransferase, triglyceride lipase, phospholipase A1 and phospholipase A2 were followed in guinea-pig lungs at 24, 48 and 72 h after food deprivation. Triglyceride lipase was elevated and phospholipase A1 and phospholipase A2 were unaffected, while the other activities decreased. The significance of these findings in relation to food deprivation is discussed.     

Acyl-CoA thioesterase 9 (ACOT9) in mouse may provide a novel link between fatty acid and amino acid metabolism in mitochondria

Acyl-CoA thioesterase (ACOT) activities are found in prokaryotes and in several compartments of eukaryotes where they hydrolyze a wide range of acyl-CoA substrates and thereby regulate intracellular acyl-CoA/CoA/fatty acid levels. ACOT9 is a mitochondrial ACOT with homologous genes found from bacteria to humans and in this study we have carried out an in-depth kinetic characterization of ACOT9 to determine its possible physiological function. ACOT9 showed unusual kinetic properties with activity peaks for short-, medium-, and saturated long-chain acyl-CoAs with highest V _max with propionyl-CoA and (iso) butyryl-CoA while K _cat/K _m was highest with saturated long-chain acyl-CoAs. Further characterization of the short-chain acyl-CoA activity revealed that ACOT9 also hydrolyzes a number of short-chain acyl-CoAs and short-chain methyl-branched CoA esters that suggest a role for ACOT9 in regulation also of amino acid metabolism. In spite of markedly different K _ms, ACOT9 can hydrolyze both short- and long-chain acyl-CoAs simultaneously, indicating that ACOT9 may provide a novel regulatory link between fatty acid and amino acid metabolism in mitochondria. Based on similar acyl-CoA chain-length specificities of recombinant ACOT9 and ACOT activity in mouse brown adipose tissue and kidney mitochondria, we conclude that ACOT9 is the major mitochondrial ACOT hydrolyzing saturated C₂-C₂₀-CoA in these tissues. Finally, ACOT9 activity is strongly regulated by NADH and CoA, suggesting that mitochondrial metabolic state regulates the function of ACOT9.     

Propionic acidemia and sodium dipropylacetate]

After administering sodium dipropylacetate to normal rats and biotin-deficient rats, we observed a slight hyperglycinemia, significant constant hyperglycinuria, but no accumulation of propionic acid in the blood or significant urinary elimination. Hepatic propionyl-CoA carboxylase activity, in vivo and in vitro, did not change, neither did sodium dipropylacetate inhibit propionyl-CoA carboxylase nor induce propionic acidemia resulting from a deficiency in this enzyme.     

Hepatic and cerebral coenzyme a contents after intravenous injection of coenzyme a in rats

Summary Hepatic CoA concentrations and contents were significantly higher in rats having received i.v. CoA injections than in control rats. Maximum hepatic CoA concentrations were found 0.5–1 h after injection. In rat brain, no increase in CoA concentration was detected after i. v. injection of CoA.Acknowledgments. We thank MissV. Godly and MissA. M. Reber for excellent technical assistance. This work was supported by grants from F. Hoffmann-La Roche & Co., AG, Basel.     

A sigmoidal relationship between liver stearoyl CoA desaturase activity and serum hormone concentrations caused by streptozocin and its antagonists

Stearoyl CoA desaturase activity in liver microsomes, and insulin, thyroxine, and triiodothyronine levels in serum were measured after administration of streptozocin (STZ) and its antagonists to rats. The effect of STZ, which caused hyperglycemia and inhibited the desaturase activity, was antagonized by 2-desoxyglucose and 3-O-methyl-glucose; 1-O-methyl-3-desoxyglucose and 1-O-methyl-3-O-methylglucose were without any effect. The enzyme activity plotted against insulin levels showed a broad sigmoidal curve, whereas the activities versus thyroid hormone levels showed steeper sigmoidal curves.     

Oyster mushroom (Pleurotus ostreatus) reduces the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat liver microsomes

The effect of dried oyster mushroom (Pleurotus ostreatus) on cholesterol (C) content in serum, in lipoproteins and in liver, and on the activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in liver microsomes, was studied in male rats (strain Wistar, initial body weight 75 g) fed on low-cholesterol (9 mg/100 g) and high-cholesterol (0.3%) diets. Addition of 5% oyster mushroom to both diets reduced significantly the C-content in serum (by 30%), in very-low- and low-density lipoproteins (in a 11 ratio to the decrease of total serum C) and in liver (by 50%), as well as the activity of HMG-CoA reductase (by more than 30%).     

A signoidal relationship between liver stearoyl CoA desaturase activity and serum hormone concentrations caused by streptozocin and its antagonists

Summary Stearoyl CoA desaturase activity in liver microsomes, and insulin, thyroxine, and triiodothyronine levels in serum were measured after administration of streptozocin (STZ) and its antagonists to rats. The effect of STZ, which caused hyperglycemia and inhibited the desaturase activity, was antagonized by 2-desoxyglucose and 3-O-methyl-glucose; 1-O-methyl-3-desoxyglucose and 1-O-methyl-3-O-methylglucose were without any effect. The enzyme activity plotted against insulin levels showed a broad sigmoidal curve, whereas the activities versus thyroid hormone levels showed steeper sigmoidal curves.     

Epithelial localization of pyruvate kinase L (ATP pyruvate phosphotransferase EC 2.7.1.40) in rat liver]

Using three methods: histoenzymatic and immunoenzymatic, stained with tetrazolium salt, and immunofluorescence, we have localized PK "L" in hepatocytes. This localization in the cytoplasm of the cells differs widely in intensity with diet or hormone administration. Maximal with animals fed on high carbohydrate diet, still elevated with a subsequent insulin administration, it decreases with a normal diet to become weaker in animals, which have fasted for 48 hrs.     

Glucose-evoked recovery of hepatic thyroxine 5'-deiodinase independent of de novo protein synthesis in fasted rat

The glucose-evoked recovery of Type I thyroxine 5'-deiodinase activity in the hepatic microsomes of fasted rat was not inhibited by either cycloheximide, puromycin or actinomycin D during 3 h after glucose feeding; however, [3H]-leucine uptake by the liver or the hepatic microsomal fraction was significantly inhibited by cycloheximide and puromycin but not by actinomycin D. These results indicate that the glucose-evoked recovery of deiodinase activity may be independent of de novo protein synthesis.     

Effect of diet on osmotic water flow across rat colon mucosa

Summary Osmotic water flow across colon mucosa was increased in rats adapted to a high protein diet (HP) compared to rats fed a high carbohydrate diet (HC). The diet-induced change of the osmotic permeability of the colon is probably a manifestation of a regulatory mechanism controlling intestinal water absorption.Supported by the Deutsche Forschungsgemeinschaft.The technical assistance of Miss Margitta Hosser is gratefully acknowledged.     

Cholesterol feeding to rats does not modulate the expression of binding sites for HDL on liver membranes

The binding of HDL, Apo-E-free, was studied in rats fed a cholesterol rich diet for 2, 4 and 7 days. Plasma cholesterol increased up to 16-fold (from 55 to 900 mg/dl); liver cholesterol was also raised, from 0.5 to 16 mg/g of tissue. The HDL binding to membrane preparations was not affected while the binding of beta VLDL was reduced to about 50% of the controls. These data show, therefore, that liver binding sites for HDL are refractory to regulation by dietary cholesterol.     

外源性干细胞因子对糖尿病胃轻瘫大鼠胃窦Cajal细胞的影响

目的探讨外源性干细胞因子（SCF）能否改善糖尿病胃轻瘫（DGP）大鼠胃窦Cajal细胞（ICC）的异常病变。方法sD大鼠随机分为实验组和对照组，实验组腹腔注射链脲佐菌素（STZ）50mg／kg并高糖高脂饲料不规律喂养构建DGP模型，对照组腹腔注射等量生理盐水并普通饲料规律喂养。成模后随机分为糖尿病组（DM组）、糖尿病＋外源性干细胞因子治疗组（DM＋SCF组）；DM＋SCF纽腹腔注射SCF0．4ug／（kg·d），共15天，对照组和DM纽每天腹腔注射等量的磷酸盐缓冲液（pH=7．4）。RT-PCR、Wester Dblot检测胃窦组织中SCF及c—kit的mRNA及蛋白表达；免疫组化、透射电镜观察胃窦组织中Cajal细胞的变化。结果DM组大鼠胃窦组织SCF及c—kit的mRNA及蛋白表达下降，Cajal细胞数量减少，细胞内线粒体肿胀、内质网扩张；予外源性SCF干预后，胃窦组织中SCF及C—kjf的mRNA及蛋白表达上调，caial细胞数量增多、超微结构明显改善。结论外源性SCF能在一定程度上改善或逆转糖尿病胃轻瘫大鼠胃窦Cajal细胞的异常病变：     

The effect of hunger on free fatty acid and corticosterone plasma levels in rats.

The time function of free fatty acids and of corticosterone in plasma in fed and fasted rats was investigated. Also a study of the influence of hypoxia on the concentration of plasma free fatty acids was carried out. Whereas fasting does not seem to stimulate lipolysis markedly before 12 h, 2 h of hypoxia elevate the free fatty acid level to its maximum. In the fasted condition, all values are significantly higher than corticosterone in the fed animal.     

A synergistic interaction between the teratogenic effect of trypan blue and dietary deficiency in the rat.

There was an increased incidence, compared to controls, of exencephaly and microphthalmia in the offspring of rats fed a vitamin D deficient diet and injected with trypan blue on day 9 of gestation. Oral vitamin D did not reverse the effect.     

In vivo inhibition of citrate cleavage enzyme by polychlorinated biphenyls

Summary Polychlorinated biphenyls (Aroclor 1254, PCB) administered in the diet (0.01%, w/v) to rats inhibited citrate cleavage enzyme. The results suggest that the decreased activity might in part account for decreased fatty acid synthesis in the livers of PCB-treated rats.This research was supported by a grant from the National Institutes of Health (ES-00040). Aroclor 1254 was a gift of Monsanto Company, St. Louis, Missouri, USA.     

Radiostrontium-Ausscheidung im Kot junger Ratten nach calciumreicher Ernährung

Summary Young immature rats of both sexes were fed with a diet either high (1.95%) or low (0.31%) in Ca content. A s.c. injection of weightless⁹⁰Sr results in a better excretion of radiostrontium with the faeces during feeding with high Ca diet. The retention of activity in the femori 30 days after injection is, in the same case, lower than by feeding with low Ca diet.     

Carcinogenicity examination of betel nuts and piper betel leaves

Summary A dry powder of betel nuts, piper betel leaves and lime was administered to rats. Epidermal thickening was frequently observed in the upper digestive tracts of rats in groups fed the betel nut diet mixed with lime and the betel leaves diet, and a forestomach papilloma was seen in 1 rat given betel leaves diet. These epidermal changes were scarcely seen in rats given either betel nut or normal diet alone.This work was supported by a grant from the U.S.-Japan Cooperative Medical Science Program     

Zinc-deficiency and activities of urea cycle-related enzymes in rats

Summary In contrast to previous reports, an increase in glutamate dehydrogenase activity and no change in arginase activity were observed in rats fed a zinc-deficient diet for 15 weeks. The discrepancies could be due to a difference in degree and duration of zinc-deficiency.We wish to thank Professor P.M. Newberne for supplying the plastic cages and ingredients for the zinc-deficient diet.     

Modulation of 3-hydroxy-3-methyl glutaryl CoA reductase by 2,3-diphosphoglyceric acid

Rat liver microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was activated by 50% at a concentration of 0.4 mM 2,3-diphosphoglyceric acid (DPG) and by 11-fold at 10 mM DPG. DPG also prevented the inactivation of HMG-CoA reductase by ATP and Mg++. Rat liver microsomal HMG-CoA reductase prepared in the presence of 1 mM DPG was significantly more active than when prepared in the absence of DPG. Activation of the enzyme by DPG and protection of the enzyme against inhibition by ATP and Mg++ by DPG were also observed with solubilized HMG-CoA reductase.