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Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 163 records · Page 9Linked to original sources

Influence of dietary fiber on lipid metabolism in meal-fed rats.

The effects of the four major components of dietary fiber--cellulose, hemicellulose, pectin and lignin--on lipid metabolism were studied in meal-fed Wistar rats maintained on a cholesterol-free semipurified diet for 21 days. Transit time was decreased and fecal weight increased compared to rats fed a fiber-free diet. Rats fed cellulose or lignin gained significantly less weight than rats fed hemicellulose or pectin. The fibers had no effect on serum cholesterol levels, but serum triacylglycerol levels were significantly higher in rats fed cellulose. Liver cholesterol levels were higher in cellulose-fed rats but liver triacylglycerol levels were highest in rats fed hemicellulose or pectin. Hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activities were highest in rats fed cellulose and pectin, respectively. Epididymal fat cell size was similar in all groups but fat cell number was highest in pectin-fed rats. Perirenal fat cell size was greatest in rats fed cellulose or lignin and fat cell number in rats fed cellulose or hemicellulose. Lipoprotein lipase activity (per 10(6) cells) was elevated in epididymal fat of rats fed pectin and in perirenal fat of rats fed hemicellulose. Carcass lipid accumulation was highest in rats fed cellulose or lignin. Rats fed cellulose accumulated significantly higher levels of carcass cholesterol and triacylglycerol. Of the fibers fed, cellulose led to an accumulation of serum, liver and carcass lipid. The four fibers fed represent purified and altered forms of cellular components and the observed effects cannot be extrapolated to diets containing foods rich in one or another of these components.

Adipose Tissue↗

Influence of trans unsaturated fats on experimental atherosclerosis in rabbits.

To test the effects of trans unsaturated fatty acids (t-FA) on atherosclerosis, lipidemia and enzyme activities, rabbits were fed a semipurified, cholesterol-free diet containing 40% sucrose, 25% casein and 14% fat for 5 months. Two experimental diets provided either 6% (high) or 3.2% (low) t-FA. The control group was fed a fat of composition similar to the two experimental diets but free of t-FA. Serum cholesterol and triglycerides were elevated in the rabbits fed 6% t-FA. Liver glycerides were also elevated in this group. The fatty acids of plasma, erythrocytes, epididymal fat, liver microsomes and liver mitochondria reflected the dietary composition. Levels of aortic atherosclerosis were identical in the three groups. There were no significant differences in activity of five hepatic enzymes: glucose-6-phosphatase (microsomal), fatty acid synthetase (cytosolic), malate dehydrogenase, beta-hydroxybutyrate dehydrogenase and monoamine oxidase (mitochondrial).

Adipose Tissue↗

Fiber, steroids, and cancer.

Fiber is a generic term for dietary components which are not metabolized by intestinal secretions. Fiber encompasses a variety of substances of unique structure having specific physical characteristics and physiological function. There are a number of epidemiological and case-control studies on diet and colon cancer, many of which suggest that dietary fiber or fiber-rich foods may exert a protective action, but the view is not unanimous. One study finds a negative correlation between cancer mortality and pentose-rich dietary fibers. Animal studies have been carried out using rats of different strain, semipurified or commercial diets, and various carcinogens administered in a variety of ways. Again, there is no unanimity. The results depend upon the type of fiber and the route of carcinogen administration. Some type of fiber bind bile acids and salts, and this property has been investigated as a means of explaining the protective action of fiber. Several recent studies in human subjects suggest that susceptibility to colon cancer is related inversely to the concentration of fecal bile acids rather than to the absolute quantity of fecal bile acids or their structure. Future studies require better standardization of protocols so that intradietary effects can be assessed.

Animals↗

Influence of beclobrate and eniclobrate on cholesterol metabolism in rats.

Two new hypocholesterolemic compounds, ethyl-(+/-)-2-[[alpha-(p-chlorophenyl)-p-tolyl]-oxy]-2-methylbutyrate (Sgd 24 774, beclobrate) and the 3-pyridinylmethyl ester (eniclobrate), have been studied in normocholesterolemic rats. The two compounds are hepatomegalic and they lower serum and liver cholesterol levels but raise liver triglyceride levels. They also reduce the percentage of esterified cholesterol present in the serum. Beclobrate enhances hepatic HMG-CoA reductase activity but does not affect cholesterol-7 alpha hydroxylase. Eniclobrate, on the other hand, increases activity of the hydroxylase but not of HMG-CoA reductase. Neither compound affects cholesterol absorption.

Animals↗

Influence of beclobrate on gallstone formation in hamsters.

Three groups of male Syrian hamsters were fed a lithogenic diet (L), L plus 0.04% ethyl-2-[4-(p-chlorophenyl) methylphenoxy]-2-methylbutyrate (beclobrate); or L plus 0.17% beclobrate. After 60 days, the percentage of hamsters with gallstones on the three diets was 28, 16 and 12, respectively. Biliary phospholipid was not affected, but biliary cholesterol and bile acid were reduced significantly in both test groups.

Animals↗

Influence of native and randomized peanut oil on lipid metabolism and aortic sudanophilia in the vervet monkey.

Vervet monkeys (Cercopithecus aethiops pygerethrus) were fed cholesterol-free, semipurified diets containing 40% sucrose, 25% casein, 15% cellulose and 14% peanut oil (PNO), randomized peanut oil (RPNO) or corn oil (CO). After 4 months, serum cholesterol and triglyceride levels, serum lecithin-cholesterol acyl transferase (LCAT) activity and plasma lipoprotein lipase (LPL) activity were similar in all groups. Livers of monkeys fed CO converted 156% more acetate and 24% more mevalonate to cholesterol than those of monkeys fed RPNO. Cholesterogenesis in RPNO-fed monkeys was enhanced compared to PNO (68% from acetate; 62% from mevalonate). Incidence of atherosclerosis was 33% in monkeys fed RPNO, 80% in those fed CO and 90% in those fed PNO. Extent of sudanophilia was lowest in aortas of monkeys fed RPNO. Incidence of arteriosclerosis was 40% in monkeys fed CO, 56% in those fed RPNO and 70% in those fed PNO. Extent of aortic surface showing arteriosclerosis was highest in monkeys fed RPNO.

Animals↗

Experimental atherosclerosis in rabbits fed cholesterol-free diets.

Rabbits were fed a semipurified, cholesterol-free atherogenic diet containing 40% sucrose, 25% casein, 14% fat, 15% fiber, 5% salt mix and 1% vitamin mix. The fats were corn oil (CO), palm kernel oil (PO), cocoa butter (CB), and coconut oil (CNO). The rabbits were bled at 3, 6, and 9 months and killed at 9 months. Serum lipids of rabbits fed CO were unaffected. Serum cholesterol levels (mg/dl) at 9 months were: CO -- 64; PO -- 436; CB -- 220; and CNO -- 474. HDL-cholesterol (%) was: CO -- 37; PO -- 8.6; CB -- 25.1; and CNO -- 7.0. Average atherosclerosis (arch + thoracic/2) was: CO -- 0.15; PO -- 1.28; CB -- 0.53; and CNO -- 1.60. Cocoa butter (iodine value 33) is significantly less cholesterolemic and atherogenic than palm oil (iodine value 17) or coconut oil (iodine value 6). The difference between the atherogenic effects of cocoa butter and palm oil may lie in the fact that about half of the fatty acids of palm oil are C 16 or shorter, whereas 76% of the fatty acids of cocoa butter are C 18 or longer.

Animals↗

Hypolipidemic drugs are inhibitors of phosphatidylcholine synthesis.

Clofibric acid (CPIB) and several other systemic hypolipidemic drugs are shown to block phosphatidylcholine synthesis by inhibiting cholinephosphotransferase (ChoPTase; CDPcholine:1,2-diacylglycerol cholinephosphotransferase, EC 2.7.8.2) and particularly lysolecithin acyltransferase (LLAcylTase; acyl-CoA:1-acylglycero-3-phosphocholine O-acyltransferase, EC 2.3.1.23) of rat liver microsomes. Whereas millimolar drug concentrations are required to affect de novo lecithin synthesis catalyzed by ChoPTase, reacylation of lysolecithin by LLAcylTase is inhibited at micromolar levels. Increasing effectiveness in ChoPTase inhibition is observed in the series CPIB, SaH-42-348, tibric acid, S-321328, WY-14643, S-8527, and DH-990, with IC50 ranging from 22 mM (CPIB) to 0.3 mM (DH-990). LLAcylTase inhibition by the hypolipidemic drugs follows the same general pattern, but IC50 concentrations range from 9 mM (CPIB) to 40 microM (DH-990). The agents inhibit ChoPTase (Ki, 25-0.25 mM) and LLAcylTase (Ki, 10-0.025 mM) noncompetitively. The data suggest that inhibition of phosphatidylcholine synthesis, particularly by the LLAcylTase pathway, may be related to a drug's effectiveness in decreasing serum triglyceride and cholesterol levels by blocking lipoprotein synthesis.

1-Acylglycerophosphocholine O-Acyltransferase↗

Trans fatty acid effects in experimental atherosclerosis.

Trans unsaturated fatty acids are formed during hydrogenation of edible oils and their consumption in the United States has increased with increasing utilization of margarines. The effect of elaidic acid and trielaidin on atherosclerosis in cholesterol-fed rabbits were studied many years ago by Weigensberg and McMillan, who found these fatty acids to be significantly more hypercholesterolemic but not more atherogenic. Jackson et al. have found that trans fatty acids are not inordinately atherogenic in swine. We have fed rabbits semipurified, cholesterol-free diets containing either 3.2 or 6.0% of trans fatty acid. The diets were slightly hyperlipidemic but no more atherogenic than the control diet. We measured the activities of five hepatic enzymes (glucose-6-phosphatase, fatty acid synthetase, malate dehydrogenase, beta-hydroxybutyrate dehydrogenase, and monoamine oxidase [EC 1.4.3.4]). The diets affected only the activity of monoamine oxidase, which was lower in the livers of rabbits fed 6.0% trans fatty acid. Vervet monkeys were fed the same diets either for 1 year or for 6 months and then returned to the control diet for 6 months. The dietary manipulations had no effect on serum or lipid levels or aortic sudanophilia. Trans fatty acid levels of the serum reflected dietary concentration. Six months after cessation of feeding of the trans fat the levels of trans fatty acids in serum were virtually normal. Trans fatty acids appear to exert a hypercholesterolemic effect but do not influence aortic atherosclerosis in rabbits or aortic sudanophilia in vervet monkeys.

Animals↗

Distribution of plasma lipids and glucose in two breeds of rabbit.

This study was undertaken to determine the frequency distribution of plasma lipid and glucose values in New Zealand White and Dutch-Belted rabbits. The results indicate that the levels of glucose, phospholipid and triglyceride were similar in the two breeds in contrast to cholesterol levels which were higher and more variable in the New Zealand White rabbit. These results are consistent with the higher incidence of spontaneous aortic lesions and more varied response to dietary cholesterol in the New Zealand White rabbit. Identification of rabbits having higher than normal fasting cholesterol levels may be valuable in the design of studies of within strain differences in cholesterol metabolism. The study also provides a useful baseline using current methods for glucose and lipid levels in the two breeds of rabbit.

Animals↗

Aortic sudanophilia an zinc-copper ratios in the liver of vervet monkeys fed different types of dietary fibre.

Vervet monkeys (Cercopithecus aethiops pygerethrus) were fed a semipurified diet containing 40% sucrose, 25% casein, 14% hydrogenated coconut oil and 15% fibre for 6 months. Alfalfa, cellulose, or wheat straw was the source of the fibre. All the diets led to aortic sudanophilia, but the group fed wheat straw had the highest copper level in the liver and the least sudanophilia. The order to severity of the sudanophilia, the ratio of zinc to copper in the fibers, and the ratio of zinc to copper in the liver were: alfalfa-fed group greater than cellulose-fed group greater than wheat straw-fed group. These findings, which may have resulted from the relatively large amount of copper in the wheat straw, are consonant with observations on lipid metabolism in other species.

Animals↗

Identification of acidic steroids in feces of monkeys fed beta-sitoserol.

Vervet monkeys were fed a suspension of beta-sitoseterol in corn oil. Acidic steroids were separated from a 4-day pool of feces and subjected, after fractionation, to gas liquid chromatography and mass spectrometry. Evidence for the presence of derivatives of 27-carboxysitosterol, 27-carboxysitostanol and 7-hydroxy, 27-carboxysitostanol is adduced.

Animals↗