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Biomedical subjects

R Kannan

Publications and source records attributed to R Kannan.

At least 109 records · Page 6Linked to original sources
PubMed1981

Apolipoprotein B is structurally and metabolically heterogeneous in the rat.

Electrophoresis of rat apolipoprotein B (apoB) on 5% polyacrylamide gels in the presence of NaDodSO4 separates three major components: PI, which comigrates with human low density lipoprotein (LDL) apoB; PII, a slightly faster-moving satellite band; and PIII, which migrates somewhat more slowly than myosin heavy chain. The proportion of PIII decreases with increasing density of the parent rat lipoprotein, from 90% an 70%, respectively, in chylomicrons and very low density lipoproteins (VLDL), to 7% in the major LDL2 (density 1.038-1.063 g/ml) fraction. A major component that comigrates with rat PIII is a marker for human chylomicron apoB, being absent from human VLDL, intermediate density lipoprotein (IDL), and LDL. Preliminary immunological and peptide mapping data show that rat apoB PI and PIII are closely related structurally, with the latter possibly being a large fragment of the former. Both peptides are synthesized in rat liver and found in Golgi secretory vesicles. Kinetic tracer experiments show that rat PI and PIII are present on separate VLDL particles, both of which are extensively removed from the circulation at the remnant stage, and that the declining PIII-to-PI/II ratios in IDL and LDL may be attributed to the more rapid turnover of PIII-containing lipoproteins at all levels, particularly within the LDL density range.

Animals↗
PubMed1981

Secretion and turnover of very low density lipoprotein triacylglycerols in rats fed chronically diets rich in glucose and fructose.

Very low density lipoproteins (VLDL) were isolated from serum after intravenous injection of rats with 1-14C-palmitic acid. These lipoproteins were in turn injected into tail veins of rats which had been fed ad libitum for 21 days on fat-free diets in which the source of carbohydrates was glucose or fructose. Groups of rats were killed at intervals up to 10 minutes after injection and the rates of decline of serum triacylglycerol (TG) and of serum VLDL-TG specific radioactivity were measured. The half-lives of VLDL-TG turnover were very short (approximately 1 minute in both groups) compared to those described previously for rats fed conventional diets or for fasted animals, but the higher plasma TG concentrations in fructose-fed rats were as reported elsewhere. From this information and the serum VLDL-TG concentrations in the two dietary groups, it was possible to estimate the rate of VLDL secretion from the liver which was found to be 75% greater in the fructose-fed rats. No differences were found in the total lipoprotein lipase activity in acetone powders of white adipose tissue from other rats fed fructose and glucose.

Adipose Tissue↗
PubMed1981

Comparison of lipogenic responses to dietary glucose in selected mouse adipose tissues.

Rates of fatty acid synthesis from glucose-carbon (glucose-C) and all other 2-carbon (2-C) units were measured in three white adipose tissues sites of fasted and fed mice, which were given a test meal containing [U-14C]glucose. Total fatty acid synthesis was measured in all mice by intraperitoneal injection of 3H2O. In fasted-refed mice the rates of lipogenesis from glucose-C and all 2-C sources were much faster in popliteal than in epididymal fat. Most of the newly synthesized fatty acids were derived from glucose-C. However, in fed-refed mice these differences between the sites were minimal, and all the absolute rates were much higher than those found in fasted-refed mice. This suggested that the adipose tissue in the three sites did not have different physiological roles. Variability in the actual rates of lipogenesis, from one experiment to another, in fasted-refed mice could be attributed to small differences in the periods of fasting, before the mice were given the test meal.

Adipose Tissue↗
PubMed1980

Fatty acid synthesis in vivo and hepatic contribution to whole-body lipogenic rates in obese Zucker rats.

We have re-examined the claim by Godbole and York, based on the effect of surgical hepatectomy (Diabetologia 14:191, 1978), that liver contributed more than 90% of the newly synthesized FA found in adipose tissue of obese rats at the end of a 1-hr pulse of 3H2O. The amount of newly synthesized FA transported via plasma VLDL from liver to adipose tissue was estimated in lean and obese Zucker rats by determining the effects of Triton WR-1339, which blocks the uptake of VLDL-TGFA into tissues. Triton treatment was found not to cause any significant change in the amount of radioactive FA found in subcutaneous/perimetrial fat tissues, carcass or liver in either chow-fed or high-glucose, fed-refed lean or obese rats, although in the fed-refed dietary state the proportion found in the liver was increased over that in the chow-fed groups. Furthermore, the amounts of newly made FA which accumulated in the plasma of Triton-treated, chow-fed and glucose-fed refed animals during this period constituted only a few percentages of those found in the adipose tissue of these animals. Thus, in contrast to the claims of Godbole and York, no significant transfer of newly made FA from liver to adipose tissue occurs during a 1-hr experiment; it follows that the amount of these FA found in different tissues at the end of that period are valid measurements of their actual lipogenic activities in situ. It is suggested that the Godbole and York results are artifacts of their surgical hepatectomy procedure.

Adipose Tissue↗
PubMed1980

Compartmental analysis of linoleate and palmitate turnover in a murine carcinoma.

We have carried out a balance study in Ehrlich ascites carcinoma in mice to determine whether large amounts of free fatty acids (FFA) could be diverted to an oxidative fate as suggested by earlier workers. At least 90% of the FFA tha turn over in the Ehrlich ascites tumor fluid are incorporated into the cell lipid esters of this carcinoma. Simultaneous with our balance study, we have compared the metabolic fate of essential and nonessential fatty acids (FA) in vivo in mouse Ehrlich ascites tumors using [1-14C]linoleic acid and [9,10-3H]palmitic acid complexed to mouse serum albumin. We followed the early disappearance of labeled FFA from the tumor system and the appearance of radioactivity in various tumor lipids and calculated rates of esterification and recycling of FA esters to FFA by cancer cells in vivo using multicompartmental analysis. We also estimated rates of "irreversible" disposal of FFA (combined rates of oxidation and transfer to host) in this tumor system. All rates for essential FA were found to be very similar to those for nonessential FA; however, some subtle differences seemed to exist; e.g., linoleate tended to disappear from the extracellular FFA pool faster than did palmitate and to appear in cellular phospholipids more rapidly than did palmitate, but the differences were not statistically significant. The major metabolic pathway for both classes of FFA was participation in an extremely rapid "futile cycle" of FA esterification (primarily into phospholipids) and hydrolysis. This cycle operates approximately 40 to 60 times faster than the rate of net FA esterification required for tumor growth (400 to 600 versus 10 nmol FA per min per 7-ml tumor). The "irreversible" disposal of FFA, based upon tracer studies with both essential and nonessential FFA, was approximately 6 times faster than the rate of FFA utilization for net growth.

Animals↗
PubMed1980

Dietary control of lipogenesis in vivo in host tissues and tumors of mice bearing Ehrlich ascites carcinoma.

We have determined rates of fatty acid (FA) synthesis from glucose carbon and all two-carbon units in control mice and in mice bearing Ehrlich ascites carcinomas. Using [U-14C]glucose and 3H2O as tracers under three nutritional conditions (24-hr fasted, 24-hr fasted-refed, and ad libitum fed-refed), we found that lipogenic regulatory mechanisms in adipose tissue and livers of mice bearing advanced tumors were similar to those of control mice. FA synthesis from glucose carbon and from all two-carbon units in livers of tumorous (8-day tumors) mice was at least as fast as that in control mice in the fasted and fasted-refed states but only about one-half that of controls in the fed-refed condition. The rate of FA synthesis from two-carbon units in carcasses of mice with 8-day tumors was not significantly different from that of controls in any of the 3 dietary states studied; however, in fed-refed mice with 8-day tumors, the rate of FA synthesis in the whole body was only one-half that of controls. The rate of FA synthesis from glucose carbon in carcasses of these tumorous mice was significantly depressed compared to that of controls in both the 24-hr-fasted and the fed-refed states. In well-nourished mice with early (5-day) tumors, the whole-body lipogenic rate from all two-carbon units was not depressed. Thus, decreased lipogenesis observed in host tissues of mice with advanced tumors is due to malnourishment; this secondarily depressed lipogenic activity probably contributes significantly to the loss of body fat that may occur at later stages of tumor growth. De novo FA synthesis in Ehrlich ascites cells, although small compared to that of the whole-body rate, was substantial in relation to lipids needed for tumor nutrition.

Animals↗
PubMed1978

The role of dietary fat and hepatic triglyceride secretion in cancer-induced hypertriglyceridemia.

Growth of Ehrlich ascites carcinoma induces hyperlipemia in mice. In the present study using male Swiss-Webster mice, we examined whether the usual elevations of plasma triglyceride levels in cancerous mice would occur in the absence of dietary fat. Hypertiglyceridemia developed at a similar rate and to a comparable degree in tumerous mice eating a fat-free (58% glucose) diet and in those fed Purina chow. Maximal hyperlipidemia was observed on day 6 or day 8 in tumorous mice fed either diet. To determine whether the endogenous cancer-induced hyperlipidemia was due to hypersecretion of triglycerides by the liver, triglyceride secretion rates were studied 0, 2, 4, 6, 8, 10, and 12 days after tumor inoculation using Triton WR-1339. The secretory rates did not increase prior to or during the development of hypertriglyceridemia in tumorous mice and were not significantly different from those of control mice. On days 10 and 12, triglyceride secretion actually decreased in tumorous mice. Other possible causes for hypertriglyceridemia are discussed in light of the present findings of undetectable differences in triglyceride secretion rates accompanying growth of Ehrlich ascites carcinoma in mice.

Animals↗
PubMed1978

Synthesis and carcinogenic activity of 5-fluoro-7-(oxygenated methyl)-12-methylvenz[a]anthracenes.

Treatment of 7,12-benz[a]anthraquinone (2) with methylmagnesium iodide or methyllithium yields mixtures of cis- and trans-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (3a,b), in which the ratio of cis to trans lies in the 3--4:1 region. Each isomer afforded high yields of 7-chloromethyl-12-methylbenz[a]anthracene (5) on treatment with hydrogen chloride in ethyl acetate. Similarly, 5-fluoro-7,12-benz[a]anthraquinone (8) afforded a mixture of cis- and trans-5-fluoro-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (9) which yielded 7-chloromethyl-5-fluoro-12-methylbenz[a]anthracene (10) on treatment with HCl. The chloromethyl compounds, 5 and 10, yielded 7-acetoxymethyl-12-methylbenz[a]anthracene (6) and 7-acetoxymethyl-5-fluoro-12-methylbenz[a]anthracene (11) on treatment with acetate ion. Hydrolysis of 6 and 11 yielded 7-hydroxymethyl-12-methylbenz[a]anthracene (7) and 5-fluoro-7-hydroxymethyl-12-methylbenz[a]anthracene (12), respectively. Since neither 11 nor 12 is appreciably carcinogenic, the carcinogenic metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) probably does not involve attack at the 7-methyl group.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Hypertriglyceridemia in Ehrlich ascites carcinomatous mice: tumor and mouse strain differences.

Ehrlich ascites carcinoma growth in mice induces hypertriglyceridemia. The degree of hypertriglyceridemia found in one laboratory (Spector's) was much greater than we observed in our laboratory. Moreover, major differences were reported with respect to fasting (no effect on tumor extracellular fluid triglyceride levels in Spector's tumor-bearing mice; marked decrease in ours). We have obtained tumorous CBA mice from Spector's laboratory and have studied them simultaneously with our Swiss-Webster mice. Triglyceride levels of the above two groups and from two controlled crossover groups, included to evaluate the influence of mouse and tumor strains on hypertriglyceridemia, were determined. The CBA mice had intense hypertriglyceridemia and high triglyceride levels in tumor extracellular fluid regardless of the subline source of ascites tumor. On the other hand, only mild hyperlipidemia was induced with both strains of tumor in Swiss-Webster mice. Thus, the variations in plasma and tumor extracellular fluid triglyceride levels probably arise from the mouse strains and not from variations in the tumor subline. Fasting caused a decrease in both plasma and tumor extracellular fluid triglyceride concentrations in CBA, as well as in Swiss-Webster mice. A mouse strain difference was also evident from a significant decrease in wet weights of adipose tissues like epididymal fat, inguinal fat, and intermuscular fat with tumor growth in the CBA strain which was not observed in the Swiss-Webster strain at the corresponding stage of tumor growth. Study of these strain diffeences may lead to an understanding of factors that regulate hyperlipidemia.

Animals↗
PubMed1976

Contribution of intermuscular fat to lipogenesis from dietary glucose carbon in mice.

We assessed the contribution of various tissues to the synthesis of fat from glucose carbon in mice during rapid lipogenic activation induced by a glucose test meal. Nibbling and gorging mice were maintained on a 58% glucose, fat-free diet. The mice were fasted 22 h and refed 5-10 muCi [U-14C]glucose (120 mg/20 g body weight) either by gastric intubation or as a test meal (58% glucose diet). The muscular carcass in both nibblers an gorgers contained more than 75% of the total radioactivity in the fatty acids derived from glucose; liver and epididymal fat pad accounted for only a small percentage. Mort than half the carcass activity was in the "muscular" tissue as neutral lipid acids. We could isolate a discrete fat body in the popliteal region of the leg muscle ("muscle fat", "intermuscular fat"). The popliteal fat converted glucose carbon to fatty acids an order of magnitude faster, per unit weight, than the epididymal fat pad or skeletal muscle. The fatty acid moiety of the triacylglycerols had the major portion of the label in the popliteal fat 2 and 6 h after ingestion of the glucose test meals. The diacylglycerol pool was active at 2 h and its activity faded at 6 h implicating its intermediary role in lipid metabolism similar to published findings in epididymal fat pad. These results indicate that fat cells associated with the muscular carcass may play a major role in the de novo synthesis of fat from dietary carbohydrate in mice.

Adipose Tissue↗
PubMed1976

Net changes in intermuscular fat before and during rapid lipogenic activation in mice.

We have attempted to measure net changes in lipid content in a discrete "intermuscular" fat pad during rapid lipogenic activation that occurs after a previously fasted mouse nibbles a glucose-rich test meal for several minutes. The popliteal fat pad was chosen for the study since it has been shown to be about an order of magnitude more active than the epididymal fat pad in the synthesis of fatty acids from glucose carbon in fasted-refed mice. We found a highly reproducible net loss in the popliteal fat pad's weight and lipid content during fasting. Net deposition of lipid occurred when 24-h fasted mice were allowed to eat a fat-free, 58% glucose diet for several minutes. In two out of three experiments lipid repletion was complete after one brief period of nibbling. Significant decreases in the net amounts of each majority fatty acid, 16:0, 16: 1, 18:1 and 18:2, were found to occur in the popliteal fat pad during a 24-h fast. After nibbling their test meal for several minutes, previously fasted mice restored their major essential fatty acid, linoleic acid, to the original fed level within 2 h, even though total lipid repletion was incomplete. Highly significant net increases in each major non-essential fatty acid were also found after brief ingestion of the test meal; however, in one experiment (incomplete repletion) only about half of the depleted fatty acids was restored. When two successive glucose test meals were eaten (2-h interval), popliteal fat converted glucose carbon to fatty acids more than twice as fast after the second feeding as after the first. However, no significant additional increment either in tissue weight or in total lipid fatty acids was found after the second test meal. Based on these findings, the possible significance of intermuscular fat in the utilization and deposition of fat is discussed.

Adipose Tissue↗
PubMed1975

Tumor extracellular triglycerides in mice during growth of Ehrlich ascites carcinoma.

Our earlier work with Swiss-Webster mice has shown that most of the lipid in Ehrlich ascites tumor extracellular fluid is in the form of free fatty acids. This finding is in direct contradiction to earlier and subsequent reports from another laboratory that has found free fatty acids to be a very minor component and triglycerides to be the major lipid of Ehrlich ascites tumor extracellular fluid. In light of these contradictory reports, we have carried out a study patterned after that of other workers, but using our Swiss-Webster mice. As predicted from our earlier study, we have found very little triglyceride in Ehrlich ascites tumor extracellular fluid. Although we could demonstrate a significant, transient hypertriglyceridemia during tumor growth, maximum plasma triglyceride concentrations were an order of magnitude lower than those reported by other workers. In addition, and again in contrast to other reports, we found that plasma triglyceride and tumor extracellular fluid triglyceride levels in tumorous mice fell significantly with fasting. Thus, interesting differences in triglyceride metabolism between mouse and/or tumor strains seem to exist. Our present findings suggest, but do not prove, that triglycerides in the tumor extracellular fluid probably are not a major source of the rapidly turning over, tumor extracellular fluid free fatty acid in our mice.

Animals↗