Hypolipidemic principle of the inflorescence stalk of plantain (Musa sapientum)

A pectin present in the juice of the inflorescence stalk of plantain(Musa sapientum) has been isolated. The material contained 32.4% hexoses and 52.5% uronic acid. On administration to rats fed both cholesterol free and cholesterol diet, this material showed significant lowering of cholesterol and triglycerides in the serum, liver and aorta. There was decreased cholesterogenesis in the liver as was evident from decreased activity of hydroxymethylglutaryl coenzyme A reductase and decreased incorporation of labelled acetate into hepatic cholesterol. Hepatic bile acids showed significant increase and there was increased fecal excretion of neutral sterols and bile acids. Release of lipoproteins into the circulation was lower. The material also caused increase in the activity of lipoprotein lipase in the heart and adipose tissue and also of plasma lecithin: cholesterol acyl transferase     

Early effects of feeding excess vitamin A: mechanism of fatty liver production in rats

Oral administration of vitamin A (30,000 IU daily for 2 days) to young rats caused a marked increase in hepatic glycogen, cholesterol, and glycerides, while hepatic phospholipid content remained almost unaltered. In an examination of the pathogenesis of the lipid accumulation, it was found that more glucose-(14)C was incorporated into liver lipids in vitamin A-fed rats, whereas incorporation of glucose-(14)C and dl-glycine-(14)C into liver protein remained unaltered. The increase in glucose-(14)C incorporation was confined to the glyceride-glycerol portion of the lipids; incorporation into liver fatty acids was inhibited. Plasma free fatty acid concentrations were elevated. It is postulated that in the vitamin A-fed rats, increased accumulation of lipids in the liver is caused by a stimulation of fatty acid mobilization from adipose tissue and enhanced formation of glycerophosphate through glycolysis, with consequent increase in the glyceride synthesis in the liver. The weight of the adrenals was increased, whereas cholesterol concentration in the gland was decreased, after administration of vitamin A to rats. This indicates adrenocortical stimulation. Interestingly enough, vitamin A feeding did not affect either the level of liver lipids or of plasma FFA in adrenalectomized rats.     

Incorporation of (2-14C)acetate into lipids of mink (Mustela vison) liver and intestine during in vitro and in vivo treatment with aflatoxin B1.

The in vitro and in vivo incorporation of (2-14C)acetate into lipids of mink (Mustela vison) liver and intestines was studied. In vitro, a dose of aflatoxin B1 as small as 7.5 mug/ml of medium reduced by 20% the amount of (2-14C)acetate incorporated into lipids of mink liver slices, whereas 180 mug caused 76% reduction in the synthesis of lipids from the radioactive precusor. Similar inhibition of lipid synthesis by aflatoxin also was observed with tissues from mink intestines and fatty liver. The degree of inhibition (19 to 84% for tissue from intestines and 19 to 64% for tissue from fatty livers) depended on the amount of aflatoxin B1 (7.5 TO 180 MUG) present in the medium. In vivo, a substantially increased amount of 14C-labeled lipids was found in the livers of mink injected with 600 mug of aflatoxin B1 per kg of body weight 20, 28, and 40 h earlier. However, no appreciable difference in incorporation of (2-14C)acetate into lipids was observed between toxin-treated and control animals when these animals were sacrificed and examined for 14C-labeled lipids at 4 and 10 h after toxin was administered.     

Mechanism of hypercholesterolemia produced by biotin deficiency

The effect of biotin deficiency on the metabolism of cholesterol was studied in rats fed cholesterol-free and cholesterol-containing diet. Biotin deficiency induced by feeding raw egg-white resulted in higher cholesterol in the serum and aorta, and higher high density lipoprotein cholesterol and low density lipoprotein + very low density lipoprotein cholesterol. In the liver, cholesterol increased only in the cholesterol diet group but not in the cholesterol-free diet group. Levels of triglycerides were lower in the biotindeficient, cholesterol-free diet group, but triglycerides were elevated in the cholesterol diet group. Concentration of bile acids in the liver and activity of lipoprotein lipase in the heart and adipose tissue were significantly decreased in the biotin-deficient rats. Release of lipoproteins into the circulation, incorporation of [1,2-¹⁴C] acetate into cholesterol, and activity of plasma lecithin: cholesterol acyl transferase were higher.     

Effects of dexamethasone on lipid metabolism in rat organs

Injecting of dexamethasone (10 mg/kg body weight) for 8 days to rats decreased the body weight and feed intake by 29 and 50%, respectively. The increase in weights of liver, heart, kidneys and testes per 100 g body weight was 55, 37, 33 and 13%, respectively. Though, in general, the triglyceride content increased in all the organs, maximum increase (9-fold) was observed in the liver. The plasma showed elevated levels of triglycerides, cholesterol and phospholipids. In hepatic mitochondrial membranes, the content of protein, phospholipids and cholesterol decreased/g tissue. The percent 14C distribution, as a part of total incorporation in nonpolar lipids, of [14C]acetate into triglycerides of liver, kidneys and testes increased significantly. The increased turnover of phospholipids in liver and heart was mainly due to increased turnover of phosphatidyl choline (PC) and phosphatidyl ethanolamine in liver and PC in heart. Turnover of phospholipids of testes was not affected.     

Lipids changes in rat tissues in experimental urolithiasis

Total lipids, free and ester cholesterol, triglyceride and phospholipids were determined in plasma, liver, kidney and intestine in control and calculi producing diet (CPD) fed rats. Cholesterol, phospholipids and triglycerides were increased in plasma while they were decreased in all the three tissues of CPD fed rats, compared to that of control. Distribution studies of phospholipids in the tissues of treated rats showed marked decrease in the concentration of the major lipids, i.e., PC, PE, PI and SPH. However, significant increase in absolute concentration as well as percent distribution of phosphatidic acid in kidney of treated rats was observed.     

Hypolipidemic effect of methanolic extract of Dolichos biflorus Linn. in high fat diet fed rats

High fat diet fed rats showed significant increased levels of plasma and tissue total cholesterol, triglycerides, free fatty acids, phospholipids, plasma LDL cholesterol and decreased level of plasma HDL cholesterol. Methanolic extract of D. biflorus administration to high fat diet fed rats showed near to normal levels of the above lipids in plasma and tissues. Higher dose of the extract (400 mg/kg body weight) showed comparable results with standard drug atorvastatin. It is concluded that the methanolic extract of D. biflorus possesses hypolipidemic activity in high fat diet fed rats.     

Genesis of fatty liver and hyperlipemia in the fetal guinea pig.

10 to 20% of [1-14C] palmitate injected into pregnant guinea pigs was recovered in lipids of their fetuses. From these data and the rate of transport of palmitate in maternal blood, it appears that placental transport of free fatty acids can account for the accumulation of lipids in late gestational fetuses. About 80% of the labeled palmitate in the fetus appeared initially in lipids of the liver. 14C appeared in plasma triglyceride fatty acids after a few minutes and subsequently accumulated in lipids of white and brown adipose tissue, suggesting that much of the palmitate deposited in adipose tissue were derived from hepatogenous triglyceride fatty acids. By contrast, 14C was usually maximal in heart and carcass lipids before it appeared in plasma triglyceride fatty acids. Lipoprotein lipase activity in fetal adipose tissue was low, and activity of cofactor protein of lipoprotein lipase in fetal blood plasma was much lower than that observed in other mammalian species. On the basis of these and earlier observations, it is concluded that the accumulation of triglycerides in liver and blood plasma of fetal guinea pigs during late gestation is at least partly the result of the large uptake of maternally derived free fatty acids by the fetal liver accompanied by rapid synthesis and secretion of triglyceride-rich very low density lipoproteins into the blood. However, limited uptake of triglyceride fatty acids in adipose tissue may contribute to the fatty liver and hyperlipemia.     

Isomers of conjugated linoleic acid decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in post-prandial adult sedentary or trained Wistar rat

The respective effects and interactions of supplementation with two conjugated linoleic acid (CLA) isomers and exercise on plasma metabolic profile, activity of lipogenic enzymes and cellularity in two adipose tissue sites, those of the liver and heart, were examined in adult Wistar rats. Rats that were either sedentary or exercise-trained by treadmill running were fed one of four diets: a diet without CLA; a diet with either 1% cis 9, trans 11 CLA or 1% trans 10, cis 12 CLA; or a mixture of both isomers (1% of each) for 6 weeks. We observed that the exercise decreased lipogenic enzyme activities in epididymal and perirenal adipose tissue. Plasma cholesterol, insulin, and leptin concentrations were lower in exercise-trained rats than in sedentary rats. The ingestion of either CLA mixture or the trans 10, cis 12 CLA increased lipogenic enzyme activities in epididymal tissue and more markedly in perirenal adipose tissue, especially in sedentary rats, and without affecting adipose tissue weight or cellularity. A similar effect of trans 10, cis 12 CLA was observed in regard to malic enzyme activity in the liver. In addition, this isomer decreased plasma lipid and urea concentrations and increased plasma 3-hydroxybutyrate levels. The ingestion of cis 9, trans 11 CLA increased fatty acid synthase activity in perirenal adipose tissue in sedentary rats and decreased plasma cholesterol and leptin concentrations. These results show that isomers of CLA decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in adult sedentary or exercise-trained rat, thus suggesting a stimulation of adipose tissue turnover.     

Metabolism of very low density lipoproteins--effect of sardine oil.

The effect of feeding fish oil on the metabolism of lipoproteins was studied in rats. Rats were fed diet containing 10% sardine or groundnut oil for 6 weeks. There was a significant decrease in the total cholesterol, phospholipids and triglycerides as well as the amount of the lipids associated with VLDL and LDL in serum in fish oil-fed rats. The synthesis and secretion of lipoproteins particularly apoB containing lipoproteins by primary cultures of hepatocytes from these rats were studied by 14(C)-acetate or 3(H)-leucine labelling. Primary cultures of hepatocytes derived from sardine oil-fed rats showed reduced incorporation of 3(H)-leucine into apoB containing lipoproteins secreted into the medium when compared to those fed groundnut oil, indicating a decreased synthesis and secretion of apoB. This was further confirmed by significantly lower incorporation of 14(C)-radioactivity into total and individual lipids of VLDL secreted into the medium, as well as that associated with different lipids in cell layer. The activity of lipoprotein lipase in adipose tissue and aorta was significantly higher in rats fed sardine oil which may cause an increased clearance of triglyceride-rich lipoproteins from circulation. These results indicate that the fish oil exerts hypolipidemic effect particularly by decreasing the synthesis and secretion of VLDL by liver and possibly by an increased clearance of triglyceride-rich lipoproteins from circulation.     

Testosterone and Regional Fat Distribution

The effects of testosterone treatment of abdominally obese men have been assessed by evaluating the following parameters: The metabolic activity of different adipose tissue regions in vivo (using lipid label as a tracer) and in vitro (measuring lipoprotein lipase(LPL) activity), the total and visceral adipose tissue mass, insulin sensitivity, fasting blood glucose, blood lipids, and blood pressure as well as prostate volume. Middle-aged men with abdominal obesity were treated with transdermal administration of testosterone (T), dihydrotestosterone (DHT) or placebo (P) during 9 months. The study was double-blind. Treatment with T was followed by an inhibited uptake of lipid label in adipose tissue triglycerides, a decreased LPL-activity and an increased turn-over rate of lipid label in the abdominal adipose tissue region in comparisons with the DHT and P groups. These effects on adipose tissue metabolism were not detected in the femoral adipose tissue region in any of the groups. T treatment was also followed by a specific decrease of visceral fat mass (measured by CT-scan), by increased insulin sensitivity (measured with the euglycemic glucose clamp), by a decrease in fasting blood glucose, plasma cholesterol and triglycerides as well as a decrease in diastolic blood pressure. In the DHT group an increased visceral mass was detected. No other changes in these variables were found in the DHT and P groups. There were no detectable changes in prostate volume (measured by ultra-sound), prostate specific antigen concentration, genito-urinary history or urinary flow measurements in any of the groups. It is suggested that T substitution to a selected group of men results in general metabolic and circulatory improvements. The prostate area needs further careful attention.     

Free fatty acid mobilization in the development of cerium-induced fatty liver

Following cerium injection to female rats: (1) Plasma free fatty acids (FFA) concentration increases during the first 24 hours, then remains constant up to 48 hours. (2) Adipose tissue lipolytic activity increases tremendously during the first 12 hours (+380%), maintaining high values throughout the study (48hrs). These modifications are followed by a time-dependent increase of total liver lipids consisting mainly of triglycerides and to a less extent of cholesterol. (3) Adrenalectomy prevented the development of cerium-induced fatty liver: plasma FFA and lipolysis failed to increase in adrenalectomized cerium-treated animals. Thus, our study demonstrates the involvement of adrenergic stimulation of adipose tissue lipase as an obligatory step in the development of cerium-induced fatty liver.     

Antihyperlipidemic effect of D-pinitol on streptozotocin-induced diabetic Wistar rats

D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant, Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study was undertaken to evaluate the effect of D-pinitol on lipids and lipoproteins in streptozotocin (STZ)-induced diabetic Wistar rats. Rats were made type II diabetic by single intraperitoneal injection of STZ at a dose of 40 mg/kg body weight. STZ-induced diabetic rats showed significant (p < 0.05) increase in the levels of blood glucose and total cholesterol, triglycerides, free fatty acids, and phospholipids in serum, liver, kidney, heart, and brain. The levels of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol were significantly increased, and the level of high-density lipoprotein (HDL) cholesterol was significantly decreased in diabetic rats Oral administration of D-pinitol to STZ-induced diabetic rats showed significant (p < 0.05) decrease in the levels of blood glucose and total cholesterol, triglycerides, free fatty acids, and phospholipids in serum, liver, kidney, heart, and brain. The D-pinitol also lowered significantly (p < 0.05) LDL and VLDL cholesterol levels and increased significantly (p < 0.05) HDL cholesterol levels in the serum of diabetic rats. Thus, the present study clearly showed the antihyperlipidemic effect of D-pinitol in STZ-induced type II diabetic rats.     

Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs

This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-alpha and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-alpha target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs (P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes (Insig)-1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-alpha in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-alpha activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.     

Opposite metabolic response to fenofibrate treatment in pregnant and virgin rats.

The level of maternal circulating triglycerides during late pregnancy has been correlated to newborns' weight in humans. To investigate the response to fenofibrate, a hypotriglyceridemic agent, in pregnant rats, 0, 100, or 200 mg of fenofibrate/kg body weight as oral doses were given twice a day from day 16 of gestation and studied at day 20. Virgin rats were studied in parallel. Liver weight was higher in pregnant than in virgin rats, and either dose of fenofibrate increased this variable in both groups. The highest dose of fenofibrate decreased fetal weight. Although plasma triglycerides decreased during the first 2 days of fenofibrate treatment in pregnant rats, the effect disappeared on day 3, and plasma triglycerides were even enhanced at day 4. In virgin rats, fenofibrate decreased plasma triglycerides throughout the experiment. Plasma cholesterol levels in pregnant rats decreased during the first 3 days of treatment, and the effect disappeared on day 4, whereas in virgin rats, values remained decreased. Changes in plasma triglycerides paralleled those of VLDL triglycerides. In pregnant rats, VLDL cholesterol levels increased while LDL cholesterol decreased with the treatment, whereas in virgin rats, cholesterol levels decreased in all lipoprotein fractions. Only in virgin rats did liver triglyceride concentration increase with fenofibrate treatment. Lumbar adipose tissue LPL was lower in pregnant than in virgin rats, and fenofibrate treatment decreased this variable in both groups. Maternal fenofibrate treatment increased fetal plasma and liver triglyceride and cholesterol concentrations.It is proposed that the opposite effects of fenofibrate treatment in virgin and pregnant rats are a consequence of both the enhanced liver capability for VLDL triglyceride production and a rebound response to the drug in the latter.     

Glycogenesis and lipogenesis from 14C-glucose in vivo in rats irradiated with fractionated doses of gamma rays

Irradiation with fractionated doses is a specific form of stress and the data concerning these problems are topical for recent radiobiology, radiology and oncology. Interest in this present paper is focused on tissue glycogenesis and lipogenesis from U-14C-glucose in vivo in rats irradiated with fractionated doses of 2.39 Gy once a week. Analyses were done after 1-6 fractions, up to total accumulated doses of 2.39, 4.78, 7.17, 9.76, 11.95 and 14.34 Gy, which means LD50/30 for this experimental model. Fractionated irradiation of rats led to glycogen deposition and increased incorporation of 14C-glucose into the liver, heart and skeletal muscles, but not into brain glycogen. The ascertained changes were not dose-dependent. 14C-glucose was incorporated into the liver and adipose tissue lipids to a small extent, and synthesis of liver cholesterol increased only after the 5th and 6th fractions. A decreased concentration of hepatic lipids, especially of cholesterol, was observed from the 3rd to the 6th fractions.     

Effect of iridoid glucoside on plasma lipid profile, tissue fatty acid changes, inflammatory cytokines, and GLUT4 expression in skeletal muscle of streptozotocin-induced diabetic rats

The present study was designed to examine the antihyperlipidaemic potential of iridoid glucoside isolated from Vitex negundo leaves in STZ-induced diabetic rats. The levels of cholesterol (TC), triglycerides, lipoproteins, free fatty acids, phospholipids, fatty acid composition, proinflammatory cytokines, muscle glycogen content, and glucose transporter 4 (GLUT4) expression were estimated in control and diabetic rats. Oral administration of iridoid glucoside at a dose of 50 mg/kg body weight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids, and phospholipids. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low density lipoprotein- and very low density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with iridoid glucoside. The fatty acid composition of the liver and kidney was analyzed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was also restored upon treatment with iridoid glucoside. Moreover, the elevated plasma levels of proinflammatory cytokines and decreased levels of muscle glycogen and GLUT4 expression in the skeletal muscle of diabetic rats were reinstated to their normal levels via enhanced secretion of insulin from the remnant β cells of pancreas by the administration of iridoid glucoside. The effect produced by iridoid glucoside on various parameters was comparable with that of glibenclamide, a well-known antihyperglycemic drug.     

The ability of bovine mammary tissue to synthesize lipids for 96 h when cocultured with liver and adipose tissue.

Explants of bovine mammary, liver, and adipose tissues were cocultured in the same well for 24, 48, 72 or 96 h and their ability to synthesize lipids was measured by the incorporation of [14C]acetate into triglycerides, free fatty acids, and phospholipids. The model was developed to study the effect of bovine somatotropin on lipid synthesis in mammary tissue, because somatotropin will not affect mammary tissue unless liver tissue is present. Somatotropin reduced incorporation by mammary tissue relative to the control. However, the rate of incorporation remained constant through 96 h with somatotropin, but steadily decreased in control mammary tissue. Phospholipid release into the media increased dramatically from 2% of that synthesized during the first 24 h to 218% of that synthesized from 72 to 96 h. The high release of phospholipids after 24 h suggests that cellular breakdown was occurring. A 24-h incubation is recommended to study lipid synthesis with this system.     

Effect of Lipoprotein-X on lipid metabolism in rat kidney

Lipoprotein-X (Lp-X) is found in the plasma of patients with familiallecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. Themajority of the patients with this disorder develop progressiveglomerulosclerosis. In this study, the effect of Lp-X on lipid metabolism inperfused rat kidney was investigated. Lp-X was isolated from plasma ofpatients with familial LCAT deficiency by sequential ultracentrifugation andgel filtration column chromatography. Rat kidneys were perfused for 1-2 hwith Krebs-Henseleit buffer containing 20 µM [1-14C]acetate or 20µM [Me-3H]choline. In the presence of Lp-X, no significant differencein the incorporation of radioactivity into triglycerides, cholesterol,phosphocholine, CDP-choline and sphingomyelin was observed. However,incorporation of radioactivity into cholesteryl esters andphosphatidylcholine was significantly elevated in Lp-X perfused kidneys. Thecontents of cholesterol, cholesteryl esters and phosphatidylcholine werealso significantly increased in Lp-X perfused kidneys. The increase in lipidcontent in the Lp-X perfused kidney is attributed to the direct depositionof Lp-X lipids into the organ. The increase in the labelling of cholesterylesters was attributed to the increase of available substrate (cholesterol)for the acyl-CoA:cholesterol acyltransferase (ACAT) reaction. The increasein phosphatidylcholine labelling was caused by a reduced turnover of thenewly synthesized labelled phosphatidylcholine during Lp-X perfusion.     

Metabolic Alterations and Increased Liver mTOR Expression Precede the Development of Autoimmune Disease in a Murine Model of Lupus Erythematosus

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.