Lipids of cultured hepatoma cells: IV. Effect of serum and lipid upon cellular and media neutral lipids

Minimal deviation hepatoma 7288C cells were cultured in a modified Swim's medium supplemented with decreasing levels of serum, lipid-free serum, lipid-free serum plus fatty acids, and other additives. Cellular and media neutral lipid classes were quantitated, the fatty acids of triglycerides and sterol esters analyzed, and the carbon number distribution of triglycerides determined. Cellular triglyceride biosynthesis virtually was inhibited when the medium was supplemented with bovine serum alone. This inhibition was not observed when the medium was supplemented with fetal calf serum alone or mixtures of fetal calf serum and bovine serum. Cells cultivated on medium supplemented with lipid-free serum plus palmitic or linoleic acids had much lower levels of free and esterified cholesterol. The fatty acid composition of cellular triglycerides and cholesterol esters differed dramatically from the corresponding media lipid classes. Except when linoleic acid was added to the medium, changes in the media serum and lipid levels had only marginal effects upon the fatty acid composition of cellular triglycerides and cholesterol esters. These data, in conjunction with earlier data that showed the media neutral lipid levels did not decrease during cell growth, indicate that these hepatoma cells utilize little or no serum triglycerides and cholesterol esters. Linoleic acid added to the medium dramatically reduced the level of 18∶1 acids in cellular triglycerides and cholesterol esters. Palmitic acid added to the medium did not change the fatty acid compositions significantly. Comparison of experimentally determined and calculated triglyceride carbon number percentages indicated a random distribution of fatty acids in this glyceride. The fatty acid composition of cellular triglycerides was similar to the composition of the cholesterol esters. The lack of characteristic and distinguishable compositions of these two classes that occur in most normal tissues suggests a loss of specificity in the lipid metabolism of this neoplasm at the class level.     

Fatty acid patterns in iron-deficient maternal and neonatal rats

To determine the effects of maternal iron deficiency on lipid composition and fatty acid patterns in offspring, rats were fed ad libitum diets containing 5 ppm iron (deficient) (n=8) or 320 ppm iron (control) (n=7) and deionized water from day-1 of gestation through day-18 of lactation. On day-2 of lactation, litters were standardized to three male and three female pups. On day-18, pups were fasted for 4 hr before tissue and blood collection. Significant changes in serum and liver lipid concentrations and fatty acid patterns were observed in deficient pups. Serum triglycerides, cholesterol and phospholipids and liver triglycerides, cholesterol, and cholesteryl esters were increased. In deficient pups, percentage total fatty acids of 14∶0, 16∶1, 18∶1, 18∶2 from serum lipids were increased; in liver, 14∶0, 18∶2, 18∶3 were increased; 18∶0 and 20∶4 were decreased in both serum and liver. Dam serum lipid levels did not differ between groups. Lipid changes observed in iron-deficient pups did not consistently reflect the milk, serum or liver lipid patterns observed in dams. Altered lipid composition and fatty acid patterns of iron-deficient pups thus appear to be of endogenous origin.     

Hypolipidemic activity of (−)-hydroxycitrate

The influence of (−)-hydroxycitrate, a potent competitive inhibitor of adenosine triphosphate (ATP) citrate lyase, on serum triglyceride and cholesterol levels, and in vitro and in vivo rates of hepatic fatty acid and cholesterol synthesis was investigated in normal and hyperlipidemic rat model systems. (−)-Hydroxycitrate reduced equivalently the biosynthesis of triglycerides, phospholipids, cholesterol, diglycerides, cholesteryl esters, and free fatty acids in isolated liver cells. In vivo hepatic rates of fatty acid and cholesterol synthesis determined in meal-fed normolipidemic rats were suppressed significantly by the oral administration of (−)-hydroxycitrate for 6 hr, when control animals exhibited maximal rates of lipid synthesis; serum triglyceride and cholesterol levels were significantly reduced by (−)-hydroxycitrate. In two hypertryglyceridemic models—the genetically obese Zucker rat and the fructose-treated rat—elevated triglyceride levels were due, in part, to enhanced hepatic rates of fatty acid synthesis. (−)-Hydroxycitrate significantly reduced the hypertriglyceridemia and hyperlipogenesis in both models. The marked hypertriglyceridemia exhibited by the triton-treated rat was only minimally due to increased hepatic lipogenesis; (−)-hydroxycitrate significantly inhibited both serum triglyceride levels and lipogenesis in this model.     

Lipid composition of morris hepatoma 5123c,and of livers and blood plasma from host and normal rats

The lipid composition of Morris hepatoma 5123c was analyzed together with that of liver and blood plasma from both normal and tumor-bearing rats. The results showed that the liver of tumor-bearing rats contained higher amounts of glycerides, cholesteryl esters, free fatty acids and phospholipids than the liver of normal rats. In the blood plasma of tumor-bearing rats, there was an increase of free cholesterol and triglycerides; this latter difference, however, was not statistically significant. Acyl chain changes in the liver of tumor-bearing rats consisted of an increase of palmitic and oleic acids and a decrease of stearic and arachidonic acids in phosphatidylinositol. Morris hepatoma 5123c contained a lower amount of triglycerides than the livers (both host and normal) and showed a significant decrease of total phospholipids when compared to the host liver. The major acyl chain changes found in Morris hepatoma 5123c compared with both normal and host rat livers were: a) a higher percentage of arachidonic acid together with a lower proportion of palmitic acid in cholesteryl esters; b) an increase of stearic and arachidonic acids and a decrease of palmitic acid in triglycerides; and c) a higher level of palmitic and oleic acids associated with a lower percentage of stearic and C₂₂ polyunsaturated acids in phosphatidylcholine.     

Quantitative and qualitative analyses of isolated lipid droplets from interstitial cells in renal papillae from various species

The lipid droplets of renal papillae homogenates from four different species were obtained by ultracentrifugation. Ca. 80–98% of the lipids (triglycerides, phospholipids, free fatty acids, and cholesterol esters) consist of triglycerides. The triglycerides were fractionated by argentation thin layer chromatography and each fraction characterized by gas liquid chromatography. No fraction contained any unique triglyceride. The fatty acid composition of the total triglycerides, as analyzed by gas liquid chromatography and ozonolysis, differed markedly from the fatty acid composition of the corresponding plasma triglycerides. The papillary triglycerides were characterized by higher concentrations of stearic acid, arachidic acid, and polyunsaturated acids with 20 or more carbon atoms. Particularly interesting was the presence in the lipid droplets of docosa-7,10,13,16-tetraenoic acid. This acid has been shown to be a major component in the cholesterol ester fraction of rat and canine adrenal lipids. In the papillary triglycerides, this acid accounted for 7%, 15%, and more than 20% of the total fatty acids in the dog, rat, and rabbit, respectively. The pig differs from these three species in having only ca. 1% of this acid. These observations suggest that the interstitial cells produce these triglycerides. This production could occur either by a transacylation from phospholipids and cholesterol esters and by a de novo synthesis from locally produced fatty acids. The possibility that the triglyceride production may be involved in a control of the prostaglandin production of the renal medulla is discussed.     

Studies on lipid biosynthesis and cholesterol content of liver and serum lipoproteins in rats fed various phthalate esters

The effect of various phthalate ester plasticizers on lipid metabolism in rats was studied in vivo and in vitro. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) inhibited (30–70%) hepatic sterologenesis from¹⁴C-acetate and¹⁴C-mevalonate in liver minces from rats fed the phthalates at a level of 2.5 mmoles/100 g of chow diet for 21 days; inhibition of¹⁴C-acetate incorporation into phospholipids, triglycerides, and steryl esters was reduced (35–70%) by DEHP and DBP feeding. In addition, serum cholesterol was lowered ca. 14 mg/dl with dietary DEHP or DBP but not with dimethyl phthalate (DMP). Hepatic total cholesterol levels were reduced significantly (31%, P<0.001) by DMP but not by DBP or DEHP. In other studies with DEHP fed at the 0.5% level in chow diets (1.3 mmoles/100 g), the incorporation (esterification) of³H-oleate into di- and triglycerides was reduced ca. 40%. Furthermore, the addition of DEHP (2%, 5 mmoles/100 g) to a semisynthetic diet containing 10% fat (hydrogenated coconut oil) resulted in changes in serum lipoprotein composition. The percentage of serum cholesterol in LDL rose from 22% to 34% while that in HDL fell from 78% to 66%; these changes occurred without net changes in serum cholesterol levels. Possible mechanisms for the inhibitory effect of phthalates on hepatic lipid biosynthesis are discussed. These studies are in partial fulfillment of the requirements for a Doctorate degree in Medical Sciences, McMaster University, Hamilton, Ontario, Canada.     

Lipid composition and peroxide levels of mucosal cells in the rat large intestine in relation to dietary fat

To examine whether dietary fat alters membrane lipid composition and peroxidation of polyunsaturated fatty acids in “non-proliferative” and “proliferative” cells in the large intestine, Sprague-Dawley rats were fed diets providing a polyunsaturated-to-saturated fatty acid ratio of 1.2 or 0.3 at a high or low level of fat intake for a 25-day period. Cell populations were isolated and the effect of dietary fat on membrane polyunsaturated fatty acid content and peroxide levels was determined. Neither fat level nor fatty acid composition of diet influenced total cholesterol, total phospholipids, and percentage of phospholipid classes in membrane phospholipids. Feeding the high fat and/or high polyunsaturated-to-saturated fatty acid ratio diet increased polyunsaturated fatty acid content of mucosal cell phospholipids. Increase in polyunsaturated fatty acid content was paralleled by a decrease in the monounsaturated fatty acid content of mucosal cell phospholipids. Membrane content of total saturated fatty acids was not significantly affected by diet. Variation in phospholipid fatty acid composition between “non-proliferative” and ”proliferative” cells was observed. Lipid peroxide levels in mucosal cell lipid fractions were altered by dietary fat treatment. Animals fed high fat diets, compared to groups fed low fat diets, exhibited higher membrane peroxide levels when results are expressed as nmol/mg protein. Higher peroxide levels were observed in mucosal cells for rats fed high polyunsaturated-to-saturated fatty acid ratio diets when results were expressed per nmol of phospholipid. It is concluded that changes in fat level and fatty acid composition of the diet alters the mucosal cell membrane lipid composition in the rat large intestine and influences susceptibility of mucosal cell lipid to peroxidation. Further research is required to delineate which dietary factors—fat level, polyunsaturated-to-saturated fatty acid ratio, or both—have a primary influence on the degree of lipid peroxidation.     

The hypotriglyceridemic effect of eicosapentaenoic acid in rats is reflected in increased mitochondrial fatty acid oxidation followed by diminished lipogenesis

The effect of eicosapentaenoic acid (EPA) on fatty acid oxidation and on key enzymes of triglyceride metabolism and lipogenesis was investigated in the liver of rats. Repeated administration of EPA to normolipidemic rats resulted in a time-dependent decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect was observed after one day of feeding whereas lowering of plasma cholesterol and phospholipids was observed after five days of treatment. The triglyceride content of liver was reduced after two-day treatment. At that time, increased mitochondrial fatty acid oxidation occurred whereas mitochondrial and microsomal glycerophosphate acyltransferase was inhibited. The phosphatidate phosphohydrolase activity was unchanged. Adenosine triphosphate:citrate lyase, acetyl-CoA carboxylase, fatty acid synthetase and glucose-6-phosphate dehydrogenase were inhibited during the 15 d of EPA treatment whereas peroxisomal β-oxidation was increased. At one day of feeding, however, when the hypotriglyceridemic effect was established, the lipogenic enzyme activities were reduced to the same extent in palmitic acid-treated animals as in EPA-treated rats. In cultured rat hepatocytes, the oxidation of [¹⁴C]palmitic acid to carbon dioxide and acid-soluble products was stimulated in the presence of EPA. These results suggest that the instant hypolipidemia in rats given EPA could be explained at least in part by a sudden increase in mitochondrial fatty acid oxidation, thereby reducing the availability of fatty acids for lipid synthesis in the liver for export,e.g., in the form of very low density lipoproteins, even before EPA induced peroxisomal fatty acid oxidation, reduced triglyceride biosynthesis and diminished lipogenesis.     

Effects of dietary saturated andTrans fatty acids on tissue lipid composition and serum LCAT activity in the rat

Groups of rats were fed from weaning with diets containing 5% by wt of hydrogenated coconut oil (HCO), safflower oil, or a concentrate of ethyl elaidate and linolelaidate (TRANS) as the sole source of dietary fat. Fatty acid composition of the lipid classes from serum, liver, heart, and kidney was determined, and the serum lecithin: cholesterol acyl transferase (LCAT) activities were assayed for each animal. Serum LCAT activity was increased by both the HCO and TRANS diets in the early stages of the development of an essential fatty acid (EFA) deficiency but was suppressed in the animals of the TRANS group as they became older. The HCO and TRANS groups exhibited changes in tissue lipid fatty acid composition, as well as reduced growth, characteristic of an EFA deficiency. Conversion of oleic acid to eicosatrienoic acid was impaired in the animals fed the TRANS diet, greatly increasing the octadecenoic acid content of the tissue lipids at the expense of eicosatrienoic acid. The TRANS diet also suppressed incorporation of eicosatrienoic acid into cholesteryl esters of tissue and serum, indicating that, when fed as the sole source of unsaturated fat,trans fatty acids influenced the metabolism of unsaturated fatty acids and cholesterol.     

Quantitative and qualitative lipid correlation in experimental endogenous hyperlipemia

The reversible endogenous hyperlipemia in dogs, elicited by the detergent Triton which was given intravenously, was used to study the interrelations of serum lipids. In the cholesterol ester fraction an increase occurs in both monounsaturated and in saturated fatty acids, excepting myristic; while a decrease occurs in polyunsaturated fatty acids. The fatty acids of cholesterol esters of normal dogs contain 22% oleic acid, and only 24% when serum lipids are increased to almost double their normal value (TC=400–500 mg/100 ml). However there is a critical level above which a rapid rise in oleic acid occurs and, in severe hyperlipemia (TC=1500 ±430 mg/100 ml), this acid constitutes almost half of the esterified fatty acid component. Since there is no evidence that Triton directly regulates fatty acid synthesis, the lipid fraction-fatty acid interrelationship may be secondary to lipid mobilization from endogenous sources. This concept is supported by the fact that the increased serum fatty acids are only those which can be synthesized by animals. It is suggested, on the basis of a marked increased of endogenously produced fatty acids, that, at critical lipid levels, shortage of polyunsaturated fatty acids from exogenous sources occurs. This might be of sufficient degree to accelerate fatty acid synthesis to meet the need for fatty acids for energy requirements. There may also be need of fatty acid for esterification of chiefly the accumulated free cholesterol split from lipoprotein by Triton. Triton-induced changes in cholesterol ester fatty acids result in patterns which closely resemble those in the adipose tissue of dog and man and in the serum of human endogenous hyperlipemia.     

Protective effect of 3-hydroxy-3-methylglutaric acid in alcohol-induced lipemia

Oral administration of 1 g of 3-hydroxy-3-methylglutaric acid (HMG) before the ingestion of whiskey and a fatty meal markedly reduced the elevation of serum triglycerides, β-lipoproteins, phospholipids, and cholesterol in man. In rats receiving an ethanol and corn oil mixture, HMG also inhibited the increase in postprandial serum and liver lipids. A comparative study of HMG and nicotinic acid in rats showed that, therapeutically, 50 mg MHG/kg body weight is equivalent to 200 mg nicotinic acid/kg body weight in offering almost total protection against lipemic effects of ethanol. U.S. Patent 3,629,449 (Dec. 21, 1971) on “Process of Combatting Hypercholesterolemia”.     

Die Hautoberflächenlipide bei der Psoriasis vulgaris (Ps) -Cholesterin- und Wachsester,Triglyceride und Fettalkohole

The Skin-Surface Lipids in Psoriasis vulgaris (Ps) - Cholesterol Esters, Wax Esters, Triglycerides and Fatty Alcohols The composition of waxes and cholesterol esters, triglycerides and alcohols of hair lipids from subjects with psoriasis vulgaris and control group was determined by gas liquid chromatography. The amount of palmitoleic acid was lower in the lipid group of the waxes and cholesterol esters in psoriasis vulgaris. Triglycerides show two different changes in the fatty acid pattern by psoriasis: 1) the composition of shorter chain fatty acids was distinct lower but 2) patients with a heavy psoriasis show an increase of the shorter chain fatty acids especially lauric acid and a decrease of the longer chain fatty acids. The analysis of the alcohols indicates that psoriatic patients possess a higher content of alcohols with 12,13 and 14 carbonatoms than normal subjects.     

N‐Stearoylethanolamine Restores Pancreas Lipid Composition in Obesity‐Induced Insulin Resistant Rats

This study investigates the protective effect of N‐stearoylethanolamine (NSE), a bioactive N‐acylethanolamine , on the lipid profile distribution in the pancreas of obesity‐induced insulin resistant (IR) rats fed with prolonged high fat diet (58 % of fat for 6 months). The phospholipid composition was determined using 2D thin‐layer chromatography. The level of individual phospholipids was estimated by measuring inorganic phosphorus content. The fatty acid (FA) composition and cholesterol level were investigated by gas–liquid chromatography. Compared to controls, plasma levels of triglycerides and insulin were significantly increased in IR rats. The pancreas lipid composition indicated a significant reduction of the free cholesterol level and some phospholipids such as phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) compared to controls. Moreover, the FA composition of pancreas showed a significant redistribution of the main FA (18:1n‐9, 18:2n‐6, 18:3n‐6 and 20:4n‐6) levels between phospholipid, free FA, triglyceride fractions under IR conditions that was accompanied by a change in the estimated activities of Δ9‐, Δ6‐, Δ5‐desaturase. Administration of N‐stearoylethanolamine (NSE, 50 mg/kg daily per os for 2 weeks) IR rats triggered an increase in the content of free cholesterol, PtdCho and normalization of PtdEtn, PtdSer level. Furthermore, the NSE modulated the activity of desaturases, thus influenced FA composition and restored the FA ratios in the lipid fractions. These NSE‐induced changes were associated with a normalization of plasma triglyceride content, considerable decrease of insulin and index HOMA‐IR level in rats under IR conditions.     

Effects of randomization of partially hydrogenated corn oil on fatty acid and cholesterol absorption,and tissue lipid levels in rats

Randomization of partially hydrogenated corn oil containing approximately 45% oftrans octadecenoic acid only slightly, but not significantly, increased the lymphatic fatty acid absorption in rats. No effect of randomization was observed on cholesterol absorption. When rats were fed these fats at the 8.8% level (with 1.2% safflower oil) for three weeks, the concentrations of serum cholesterol, and serum and liver phospholipid were significantly higher in randomized fat than in control fat, which was composed of 9% high-oleic safflower oil and 1% palm oil. Liver cholesterol tended to be higher in randomized fat. In contrast, nonrandomized fat was not hyperlipidemic compared to control fat. Although the fatty acid composition of liver phospholipids suggested a possible interference oftrans fatty acid with the metabolism of linoleic acid to arachidonic acid, there was no effect of randomization. In the two hydrogenated fat groups,trans octadecenoic acid was incorporated and distributed similarly in adipose tissue triacylglycerol. These observations indicated that randomization of partially hydrogenated fat is not beneficial to various lipid parameters in rats.     

Dietary oligofructose lowers triglycerides,phospholipids and cholesterol in serum and very low density lipoproteins of rats

The present study was aimed at answering the question why feeding rats an oligofructose (OFS) supplemented diet could cause a significant reduction in plasma lipid levels. Daily administration of a 10% (w/w) OFS-containing diet to normolipidemic male rats resulted in a decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect was observed after one week and lasted for at least 16 wk and was associated with a reduction in plasma very low density lipoproteins, indicating that the hypolipidemic effect of OFS may be due to changes in liver lipid metabolism. We therefore tested whether OFS feeding modified the capacity of the liver to synthesize triglycerides from free fatty acids. Hepatocytes isolated from livers of control and OFS-fed rats were incubated in the presence of [1-¹⁴C]palmitate, and both intracellular and extracellular [¹⁴C]triglyceride formation were quantified. We found that chronic feeding of an OFS-supplemented diet to rats significantly reduced the capacity of isolated hepatocytes to synthesize triglycerides from palmitate. The results suggest that, like other soluble dietary fibers, OFS significantly alters liver lipid metabolism, resulting over time in a significant reduction in plasma triglyceride, phospholipid and cholesterol levels.     

Effects of dietary n−3 fatty acid-enriched chicken eggs on plasma and tissue cholesterol and fatty acid composition of rats

The purpose of this study was to examine the effects of feeding n−3 polyunsaturated fatty acid (PUFA)-enriched chicken eggs on plasma and liver cholesterol levels and fatty acid composition in rats. Eggs were collected from laying hens fed diets containing 10% flax seed (Hn−3), 12% sunflower seed (Hn−6), or wheat and soybean meal control (CON). Yolk powders were prepared and fed at the 15% level to weanling female Sprague-Dawley rats for 28 days. Consumption of n−3 PUFA-enriched yolks significantly reduced both plasma and liver total cholesterol. Liver total lipids and phospholipids of rats fed Hn−3 diet were enriched with linolenic, eicosapentaenoic, and docosahexaenoic acids with a concomitant reduction of arachidonic acid in liver phospholipids. The plasma cholesterol of rats fed yolk powders enriched with n−6 PUFA (mainly linoleic acid) was reduced to the same extent as in those fed the n−3 enriched, but the liver cholesterol was significantly increased, indicating differential effects of dietary n−3 and n−6 PUFA. The results demonstrated that the cholesterolemic and tissue lipid modulating properties of chicken eggs could be modified in a favorable way by altering the fatty acid composition of yolk lipids through manipulation of laying hen diets.     

Dietary Hyodeoxycholic Acid Exerts Hypolipidemic Effects by Reducing Farnesoid X Receptor Antagonist Bile Acids in Mouse Enterohepatic Tissues

Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid‐supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl‐CoA carboxylase, fatty acid synthase, and stearoyl‐CoA desaturase‐1. Hyodeoxycholic acid administration markedly changes the ratio of FXR‐antagonist/FXR‐agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration.     

The lipids of human pancreas with special reference to the presence of fatty acid methyl esters

Total lipids were extracted from human pancreas with chloroform-methanol, chloroform-methanol following acidification, and benzene. A similar proportional amount of total lipid was obtained by each procedure. Regardless of the method of extraction (i.e., whether or not methanol was present), a small proportion (about 1%) of the total lipid was found to consist of fatty acid methyl esters. Triglycerides constituted the major fraction (about 80%) of the pancreatic lipids; in addition to methyl esters, the remaining lipids comprised free fatty acids, phospholipids, cholesterol esters, and traces of free cholesterol. In general, each class of lipid had a similar over-all fatty acid composition with palmitic and oleic acids as predominant components. The methyl esters had a relatively high content of linolenic acid, and the free fatty acids contained a notably high proportion of palmitic acid, in each case accompanied by a corresponding decrease in the proportion of oleic acid present.     

Studies of lipid class and fatty acid profiles of rat mammary tumors induced by 7,12-dimethylbenz(a) anthracene

The lipid class and fatty acid composition profiles of mammary glands of female rats fed a nutritionally adequate diet are compared to those of tumors induced in the mammary glands by intravenous injection of dimethylbenz(a)anthracene of animals fed the same diet. Ca. 95% of the lipids of the mammary glands of the control group of animals consisted of triglycerides; glycolipids and phospholipids were present in only minor amounts. In contrast, the lipids of the mammary tumors contained much lower amounts of neutral lipids and higher concentrations of phospholipids. The glycolipid fraction was a minor component of both tissues but differed greatly in composition. The composition of the phospholipid and neutral lipid fractions, particularly the latter, of the mammary tumors also differed from that of the mammary glands of the control animals. The neutral lipids of the tumor tissues contained elevated levels of free fatty acids and cholesterol and much lower concentrations of triglyceride compared to the mammary gland lipids. Differences also were observed in the fatty acid composition of tumor and mammary gland lipid. The greatest differences occurred in the concentrations of polyunsaturated fatty acids which were generally much higher in the tumor lipids.     

Changes in serum lipids in rats treated with oral cooper

Disturbances in lipid metabolism during copper deficiency in rats are well recognized. Copper deficiency is associated with the spontaneous retention of hepatic iron. Previous studies have reported that hypercholesterolemia and hypertriglyceridemia are associated with elevated hepatic iron concentrations in copper deficient rats. There was a direct relationship between the magnitude of blood lipids and the concentration of hepatic iron. Based on these data, it has been hypothesized that iron was responsible for the development of lipemia of copper deficiency. In this study was determined the effect of increasing doses of Cu(10, 20 and 50 ppm) in the diet, on the serum total lipids, total cholesterol, triglycerides (triacylglicerols), phospholipids, non-esterified fatty acids (NEFA) and liver iron and zinc concentrations in normal rats. The results were compared with normal rats that received a balanced diet containing 0.6 and 6 ppm of Cu, respectively. The results show that Cu-supplement diminished the cholesterol and triglyceride serum levels, increased the level of phospholipids, NEFA and concomitantly decreased the hepatic concentrations of Fe and Zn. There was a statistically significant (p < 0.05) simple correlation between triglycerides and liver Fe (r = 0.917; R2 = 64.03%), cholesterol and liver Zn (r = 0.872; R2 = 76.07%), cholesterol and liver Fe (r = 0.995; R2 = 99.10%), liver Fe and liver Cu (r = -0.612), liver Fe and liver Zn (r = 0.837), liver Cu and liver Zn (r = -0.612), and serum triglycerides and liver Zn (r = 0.967). The mechanism(s) by which Fe and Zn determine these changes is not known; none of the enzymes that act in cholesterol and triglyceride metabolism and biosynthesis require Fe and/or Zn. The increase of NEFA is due to changes in the process of lipolysis and re-esterification of the fatty acids in blood. However, additional studies are needed for the precise mechanisms of this interrelationships to be clarified.