Search PubMed⌕ Search

Biomedical subjects

G A Dhopeshwarkar

Publications and source records attributed to G A Dhopeshwarkar.

At least 19 recordsLinked to original sources
PubMed1984

Restriction of maternal food intake inhibits fatty acid activation in developing rat hearts.

We studied the effect of restricting the diet of pregnant and lactating rats on the beta-oxidation of fatty acids by the developing heart in suckling pups. Control pregnant rats were fed a stock diet ad libitum. For the experimental group, food was restricted to half of the control intake on the seventh day of pregnancy and continued through lactation. The pups on the restricted diet were significantly smaller than the controls. At postnatal days 5, 14 and 21, the beta-oxidation of [1-14C] palmitate by heart homogenates was determined in the presence of ATP, carnitine and CoA. At day 21, the production of 14CO2 was 60% lower in the group on the restricted diet. Consequently, the possibility of inhibiting activation or intramitochondrial transport of fatty acids by heart mitochondria was studied in vitro using [1-14C] palmitate, [1-14C] palmitoyl CoA and [1-14C] palmitoyl carnitine. With [1-14C] palmitate, the rate of 14CO2 produced was 2464 +/- 317 cpm/mg protein/min for the control and 1682 +/- 91 for the restricted diet group. With [1-14C] palmitoyl CoA and [1-14C] palmitoyl carnitine, the oxidation rate of the experimental group was similar to control values, showing clearly that the inhibition of oxidation was from a problem with activation. A significant decrease in palmitoyl CoA synthetase activity in the heart homogenates and mitochondria of the diet-restricted pups took place.

Animals↗
PubMed1983

Differences in the fatty acid profile and beta-oxidation by heart homogenates of rats fed cis and trans octadecenoic acids.

Female Wistar rats were fed a fat-free diet containing either 5% partially hydrogenated corn oil (52.2% elaidate) or 5% oleic acid (67% oleate) with 8.6% linoleate providing 1% of calories 2 weeks before mating and were maintained on this diet throughout pregnancy and lactation. Fatty acid analysis of the developing organs as well as beta-oxidation by heart homogenates with [1-14C]palmitate, [1-14C]elaidate and [1-14C]oleate of the developing male and female progeny were determined and compared with age-matched controls on a stock diet. Results show that irrespective of the cis and trans 18:1 in the diet, the maternal plasma at term contained mostly cis 18:1, with 5% trans for the rats on the trans diet. The placenta and fetal liver contained 40 and 60% less trans, respectively, than did the maternal plasma. trans 18:1 was not detected in fetal brain or heart. Regardless of diet or sex, the order of preference for the heart was palmitate greater than elaidate greater than oleate. There was an increase in the rate of beta-oxidation of all the substrates, especially in the females on the trans diet, suggesting a stimulation of one or more of the enzymes involved. Above all, the myocardium showed a unique capacity to retain n-6 and n-3 fatty acids when the levels of these decreased in the serum.

Animals↗
PubMed1982

Trans fatty acids: transport and positional specificity in rat placental lecithin.

Differences in positional incorporation of trans and cis isomers of octadecenoic and octadecadienoic acids in placental lecithin of rats was demonstrated. A 14C-labeled albumin complex of elaidic, oleic, linoelaidic, or linoleic acid was injected into the jugular vein of pregnant rats. 6 h later 45-64% of the total radioactivity in placental lipids was found in phospholipids (PL), with a major portion of the label incorporated into choline phosphoglycerides (CPC). Following hydrolysis of placental CPC by phospholipase A2, distribution of radioactivity within isolated fatty acids and lysolecithin suggested preferential incorporation of t,t-18:2 at position 2 and a nearly equal distribution of t-18:1 at positions 1 and 2.

Animals↗
PubMed1981

Thyroid control over biomembranes: VI. Lipids in liver mitochondria and microsomes of hypothyroid rats.

The lipids of liver mitochondria prepared from normal rats and from rats made hypothyroid by thyroidectomy and injection with 131 INa contained similar amounts, per mg protein, of total lipids, phospholipids, neutral lipids and lipid phosphorus. Hypothyroidism caused a doubling of the relative amounts of mitochondrial cardiolipins (CL; to 20.5% of the phospholipid P) and an accompanying trend (although statistically not significant) toward decreased amounts of both phosphatidylcholines (PC) and phosphatidylserines (PS), with phosphatidylethanolamines (PE) remaining unchanged. The pattern of elevated 18:2 fatty acyl content and depleted 20:4 acyl groups of the mitochondrial phospholipids of hypothyroid preparations was reflected to varying degrees in the resolved phospholipids, with PC showing greater degrees of abnormality than PE, and CL showing none. Hypothyroidism produced the same abnormal pattern of fatty acyl distributions in liver microsomal total lipids as was found in the mitochondria. Hypothyroid rats, when killed 6 hr after injection of [1-14C] labeled linoleate, showed the following abnormalities: the liver incorporated less label into lipids, and converted 18:2 not exclusively to 20:4 (as normals do) but instead incorporated the label mainly into saturated fatty acids. These data, together with the known decrease in beta-oxidation, suggest that hypothyroidism involves possible defective step(s) in the conversion of 18:2 to 20:4.

Animals↗
PubMed1981

Lack of catabolism of brain cholesterol.

Since direct intracranial injections of precursors indicate that cholesterol is synthesized in the brain at all ages, there must be a mode of disposal also. The sterol nucleus itself is not degraded by mammalian systems but the side chain can be metabolized. [26-14C] cholesterol was therefore injected directly into the brain of 8- to 19-day-old rats which were sacrificed at the end of 24 hr, 1 week and 2 weeks after injection. The results indicate that, irrespective of the interval between injection and sacrifice, all of the radioactivity was found in the free cholesterol or the cholesterol component of the sterol esters. No radioactivity was found in the fatty acids of the phospholipids. We therefore conclude that the side chain of the cholesterol does not get metabolized to propionyl CoA, which in turn, could lead to fatty acid synthesis. Radioactivity in the serum, even after 2 weeks, indicates that there must be a slow but steady exchange between the brain and the blood that would explain the route of exit for brain cholesterol.

Animals↗
PubMed1981

Positional specificity of trans fatty acids in fetal lecithin.

Differences in the positional incorporation of 9-trans[1-(14)C] octadecenoic (elaidic) and 9-trans,12-trans[1-(14)C] octadecadienoic (linoelaidic) acids in fetal lecithin of rats were demonstrated. On the 20th day of gestation, a 14C-labeled albumin complex of elaidic or linoelaidic acid was injected into the jugular vein of pregnant rats. For comparative purposes, 9-cis[1-(14)C] octadecenoic (oleic) or 9-cis,12-cis[1-(14)C] octadecadienoic (linoleic acid) was injected into the maternal circulation of rats. Animals were killed 6 hr later. Distribution of label in total lipids and phospholipids (PL) of fetal issue was measured by TLC. Irrespective of the label, the highest percentage of total radioactivity was associated with PL-59 to 67%. Within PL, the major portion of radioactivity was found in choline phosphoglycerides (CPG)-53 to 67%, and in ethanolamine phosphoglycerides (EPG)-18 to 33%. While linoelaidic acid was predominantly esterified in the 2-position of CPG, elaidic acid was nearly equally distributed between positions 1 and 2 of lecithin. Distribution of radioactivity within fatty acid methyl esters (FAME) of CPG measured by radio-GLC suggested that oleic and possibly linoleic acids may be converted to nervonic and arachidonic acid, respectively, in the rat by the 20th day of gestation. Following injection of elaidate, radioacivity of FAME was distributed between palmitate and elaidic acid indicating that rat fetal tissue may metabolize elaidic acid via beta-oxidation. In contrast, following injection of linoelaidate, radioactivity of FAME was primarily associated with tt-18:2, suggesting little biotransformation to other fatty acids by fetal tissues.

Animals↗
PubMed1981

Effect of essential fatty acid deficiency on maternal, placental, and fetal rat tissues.

Prolonged dietary deprivation is needed to produce essential fatty acid (EFA) deficiency. But lack of EFA also impairs reproductive function. Inclusion of small amounts of linoleic acid in the diet can overcome this difficulty; further, if large amounts of oleic acid are included in the diet, this competes with the utilization of 18:2 producing EFA deficiency. Using this approach, female rats were fed a fat-free diet containing 5% oleic acid w/w (with 2-3% 18:2) as the only source of fat for 4 months. They were mated and on the 21st day of gestation, the fatty acids of fetal tissues, placenta, maternal liver and plasma were analyzed and compared to controls on a stock diet. Fetuses from the experimental group were smaller and contained higher amounts of 18:1 and 20:3 omega 9 indicating EFA deficiency. The omega 6 fatty acids in the polar lipids of placenta of the EFA-deficient group were not significantly lower than the controls, in spite of lower concentrations in the maternal plasma, suggesting a unique capacity of the placenta to concentrate omega 6 fatty acids, which in turn may be utilized for prostaglandin synthesis needed for inducing labor and other vascular changes in the fetus.

Animals↗
PubMed1980

Placental transport of trans fatty acids in the rat.

Placental transport of 9-trans [1-14C] octadecenoic (elaidic) and 9-trans,12-trans [1-14C] octadecadienoic (linoelaidic) acids was demonstrated in rats. On the 18th day of gestation, a 14C-labeled albumin complex of elaidic or linoelaidic acid was injected into the jugular vein of pregnant rats. For comparison, 9-cis [1-14C] octadecenoic (oleic) or 9-cis,12-cis [1-14C] octadecadienoic (linoleic) acid also was injected into the maternal circulation of rats. All animals were sacrificed 1 hr following injection. Lipid composition and distribution of label were determined in maternal plasma, placental and fetal tissues. Differences in specific activities of plasma, placental and fetal total lipids indicated a decreasing concentration gradient for both cis and trans isomers of octadecenoic and octadecadienoic acids. Distribution of radioactivity in various lipid components was determined by thin layer chromatography. Irrespective of the label, the highest percentage of total radioactivity was carried by triglycerides (TG) in maternal plasma (approximately 60-80%), and was incorporated mainly in phospholipids (PL) of fetal tissue (approximately 50-60%). A nearly equal distribution of the label was found between PL and TG of placental lipids (approximately 40%). Radioactivity of fatty acid methyl esters (FAME) determined by radio-gas liquid chromatography indicated that after injection of linoelaidate, radioactivity of maternal plasma, placental and fetal tissue FAME was associated only with t,t-18:2. Following injection of elaidate, all the radioactivity in placental FAME was associated with t-18:1; however, in fetal tissues, the label was distributed between 16:0 and t-18:1. These findings suggest that, in contrast to linoelaidic acid, rat fetal tissues can metabolize elaidic acid via beta oxidation to form acetyl CoA and palmitic acid.

Animals↗
PubMed1979

Lipogenesis in the developing brain: utilization of radioactive leucine, isoleucine, octanoic acid and beta-hydroxybutyric acid.

Incorporation of radioactivity from intracranially injected radioactive leucine, isoleucine (ketogenic amino acids), octanoic acid and beta-hydroxybutyric acid into the brain lipids of 15 to 16 day-old rats was examined. The results showed that radioactivity from all the above precursors was incorporated into brain lipids. Radioactivity from injected isoleucine was incorporated into odd numbered fatty acids indicating an alternate pathway to alpha-oxidation for the biosynthesis of these fatty acids in the brain. For some as yet unclear reasons, a substantial portion of the radioactivity from injected octanoic acid was incorporated into free fatty acids. Utilization of these compounds for providing carbon for lipogenesis during development under unstressed normal conditions is discussed.

Animals↗
PubMed1979

Trans fatty acids: positional specificity in brain lecithin.

Fifteen-day-old rats were divided into three groups: one group received an intracerebral injection of 5 microCi of 9-trans,12-trans [1-(14)C] octadecadienoic acid; the second group was given 5 microCi of the same compound plus an equal wt of nonradioactive all cis arachidonic acid; the third group was given 5 microCi of 9-trans [1-(14)C] octadecenoic acid. All animals were sacrificed 8 hr after injection. Glycerophosphocholine (GPC) was isolated and partically deacylated with phospholipase A2 from Crotalus Adamanteus venom. The results of this study were as follows: 1) after t[1-(14)C]18:1 injection, there was twice as much radioactivity in the 1-position as in the 2-position; 2) when tt[1-(14)C] 18:2 was injected, more than 90% of the total radioactivity was found in the 2-position; 3) following tt[1-(14)C]-18:2 + nonradioactive arachidonate injection, ca. 75% of the total radioactivity still remained in the 2-position; and 4) all of the injected [1-(14)C]-tracers showed evidence of undergoing beta-oxidation to form acetyl-CoA, which was converted to radioactive palmitate. The possibility is discussed that the observed distribution pattern of the injected radioactive tracers may be attributed to tissue metabolic specificity. Ramifications of the deposition of dietary trans fatty acids in the brain during the developmental stage of the central nervous system are also discussed.

Animals↗
PubMed1976

Biosynthesis of polyunsaturated fatty acids in the developing brain: I. Metabolic transformations of intracranially administered 1-14C linolenic acid.

Thirteen-day old rats were given intracranial injections of 1-14C linolenic acid (all cis 9, 12, 15 octadecatrienoic acid) and were sacrificed after 8 hr. Analysis of brain fatty acids showed that 16:0, 18:0, 18:1, 18:3, 20:3, 20:4, 20:5, 22:5, and 22:6 were labeled. The total fatty acid methyl esters were separated into classes according to degree of unsaturation on a AgNO3:SiO2 impregnated plate. The bands were scraped off and the eluted fatty acids were first analyzed by radio-gas liquid chromatography and then subjected to reductive ozonolysis to determine double bond position. The saturated acids, 16:0 and 18:0, as well as the monosaturated 18:1, must have been formed from radioactive acetate produced by beta oxidation of the injected linolenate. Among the polyunsaturated fatty acids, the triene fraction was characterized and identified as 18:3 omega3 (delta9, 12, 15), the starting material, and 20:3 omega3 (delta11, 14, 17); the tetraene fraction was identified as 20:4 omega3 (delta2, 11, 14, 17); the pentaene fraction was identified as 20:5 omega3 (delta5, 8, 11, 14, 17) and 22:5 omega3 (delta7, 10, 13, 16, 19); and, finally, the hexaene fraction was shown to be 22:6 omega3 (delta4, 7, 10, 13, 16, 19). The biosynthesis of these omega3 family fatty acids in the brain in situ is discussed.

Aging↗