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Biomedical subjects

R Fears

Publications and source records attributed to R Fears.

66 records · Page 4Linked to original sources
PubMed1980

Tryptophan and the control of triglyceride and carbohydrate metabolism in the rat.

1. Hepatic fatty acid synthesis, measured in vivo using 3H2O, was increased by a single dose of L-tryptophan (50 mg/kg body-weight) to both fed and fasted rats and by a supplement of tryptophan to the diet (2.5 g/kg diet for 7 d) when the rats were killed midway through the feeding period. 2. Additional dietary tryptophan was hypotriglyceridaemic in normal rats but exacerbated the hypertriglyceridaemia in rats when lipoprotein clearance was impaired 24 h after an injection of Triton WR 1339 (Chromatography Services Co., Birkenhead, Cheshire). 3. The effects of tryptophan on hepatic fatty acid synthesis and the concentration of serum triglyceride were not directly related to the action of the amino acid on gluconeogenesis. A lack of correlation between inhibition of gluconeogenesis and enhancement of lipogenesis was confirmed using mercaptopicolinic acid, a specific inhibitor of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). 4. DL-Tryptophan itself did not provide a significant contribution of substrate to the total rate of lipogenesis. Other possible explanations for the activity of tryptophan noted in the present experiments are discussed. 5. In conclusion, moderate intakes of tryptophan affect fatty acid and triglyceride metabolism under physiological conditions and it is proposed that the amino acid may be involved in the control of lipid metabolism in a variety of metabolic states.

Animals↗
PubMed1979

Evidence for the operation of the extrahepatic lipoprotein receptor system in vivo in rats. Effect of dietary cholesterol and orotic acid, alone or in combination, on the rate of synthesis of cholesterol and fatty acid in various tissues, measured by using 3H2O.

1. The biosynthesis of cholesterol in vivo was studied at a number of tissue sites in rats by using 3H2O as precursor. Overall, the mass of cholesterol synthesized was in good agreement with the rate of cholesterogenesis, as determined by kinetic analysis of cholesterol specific-radioactivity-time curves after administration of radiolabelled cholesterol. 2. Dietary cholesterol increased the circulating concentration of cholesterol and inhibited endogenous cholesterogenesis, with concomitant increases in the concentration of esterified cholesterol, in all tissues studied. Addition of ororic acid to the cholesterol-supplemented diet tended to reverse each of these changes in extrahepatic tissues. 3. The co-ordinated change in cholesterol biosynthesis and esterification, with no change in total cholesterol content, in extrahepatic tissues, is attributed to control by receptor-mediated lipoprotein uptake. 4. Further reduction of the concentration of the apoprotein B-containing lipoproteins by addition of orotic acid to a diet without supplementary cholesterol did not further enhance cholesterogenesis. We consider that the relatively high rates of extrahepatic cholesterogenesis in normolipidaemic rats are attributable to the low concentration of low-density lipoprotein.

Animals↗
PubMed1978

The hypercholesterolaemic effect of caffeine in rats fed on diets with and without supplementary cholesterol.

1. The effect of caffeine (2.5 g/kg diet) on lipid metabolism was examined in rats fed on a stock (low-cholesterol) diet or on a cholesterol plus cholic acid-supplemented (high-cholesterol) semi-synthetic diet. 2. When caffeine was induced in the stock diet fed to rats for 7 d, there was a moderate but significant increase in the concentration of serum cholesterol compared to the levels observed in the control rats. This change can be accounted for by the increase that was observed in the rate of cholesterogenesis in the liver. 3. After 25 d of caffeine in the stock diet, hepatic cholesterogenesis was still increased but the concentration of serum cholesterol was now the same as in the control rats. During the experimental period there was a progressive increase in the faecal excretion of neutral sterols in the rats receiving caffeine. 4. When caffeine was added to a cholesterol plus cholic acid-supplemented diet, there was a marked increase in the concentration of serum cholesterol but hepatic cholesterogenesis was now reduced. 5. Caffeine in the high-cholesterol diet appeared to delay, but probably did not reduce, the absorption of an oral dose of radio-labelled cholesterol. This conclusion was confirmed using rats which had not previously received either caffeine or cholesterol in the diet. 6. When the effect of caffeine in the high-cholesterol diet was investigated during a 24 h period, an exacerbation of the hypercholesterolaemia was seen only at certain times. 7. After a 4-month period of feeding rats on the caffeine-supplemented high-cholesterol diet, histological examination did not detect any damage to the heart and aorta. 8. The metabolic regulations involved in the effects of caffeine in the two diets are discussed and the relevance of the present results to observations made with human subjects is considered.

Animals↗
PubMed1978

The participation of ethyl 4-benzyloxybenzoate (BRL 10894) and other aryl-substituted acids in glycerolipid metabolism.

Investigation into the mechanism of action of BRL 10894 (ethyl 4-benzyloxybenzoate), a compound possessing hypolipidemic activity in the rat, disclosed participation in glycerolipid metabolism. In the presence of BRL 10894, an abnormal metabolite was synthesized in vitro using liver slices or rings of small intestine with glycerol, palmitate, or monoolein as substrate, and using adipose tissue with pyruvate as substrate. Esters related chemically to BRL 10894 and other pharmacologically active acids (e.g., ibuprofen) also produced abnormal metabolites in vitro. With BRL 10894 in the diet, a similar metabolite was produced in vivo in rats and accumulated in adipose tissue. Chemical characterization of the material synthesized in vivo showed that the metabolite was a triglyceride in which one fatty acid moiety was substituted by the acid of BRL 10894. Additional proof of this structure was obtained by comparison with reference material synthesized in our laboratories. The study of the initimate involvement of exogenous acids in glycerolipid turnover is of value in the characterization of pharmacologically important acids and may be of use in achieving a greater understanding of certain aspects of lipid metabolism.

Adipose Tissue↗
PubMed1977

Hypolipidemic analogues of ethyl 4-benzyloxybenzoate.

A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure--activity relationships are discussed in terms of cholesterol-lowering activity together with effects on weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl-4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoates, and 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.

Animals↗
PubMed1976

Studies on the response of cholesterol biogenesis in feeding in rats: evidence against the existence of diurnal rhythms.

1. The biosynthesis of cholesterol was studied, by using various precursors, in rats subjected to several dietary regimes. 2. The use of 3H2O as a substrate to demonstrate differences in cholesterogenesis under various conditions was validated by using rats fed on cholesterol or cholestyramine. Cholesterol feeding resulted in decreased cholesterogenesis, whereas cholestyramine caused an increase. 3. With acetate as precursor, the biosynthesis of both digitonin-precipitable sterol and fatty acids was increased in vitro in response to a meal. 4. In rats fed ad libitum, hepatic cholesterogenesis was increased at midnight relative to mid-morning as measured by using acetate precursor in vitro. However, no such difference was found by using 3H2O in vivo. 5. The lipogenic response was measured in meal-fed rats by using 3H2O or octanoate in vivo. In contrast with findings with acetate in vitro, no postprandial stimulation of cholesterogenesis was seen with either 3H2O or octanoate as precursor, whereas fatty acid biosynthesis from either substrate was increased. 6. These findings are discussed with respect to current theories about the circadian rhythm of cholesterogenesis. Such theories are based on experiments using isolated enzyme measurements or non-physiological precursors such as acetate. 7. It is considered that results obtained with 3H2O give an accurate representation of cholesterogenesis under various conditions, and it is therefore suggested that hepatic cholesterogenesis in rats is not subjected to the same degree of diurnal rhythm as has previously been believed.

Acetates↗