The cholesterol-lowering effect of guar gum is not the result of a simple diversion of bile acids toward fecal excretion

The effects of partially hydrolyzed, nonviscous, guar gum (PHGG) on cholesterol metabolism and digestive balance have been compared with those of native guar gum (GUAR) in rats adapted to 0.4% cholesterol diets. Both types of guar gum elicited acidic fermentations in the large intestine, but only GUAR effectively lowered plasma cholesterol (P<0.001), chiefly in the triglyceride-rich lipoprotein fraction. The biliary bile acid excretion was significantly enhanced in rats fed GUAR (P<0.05), as well as the intestinal and cecal bile acid pool (P<0.001). In rats fed GUAR and to a lesser extent in those fed PHGG, the fecal excretion of bile acids and neutral sterol was higher than in controls (P<0.01). The digestive balance (cholesterol intake-steroid excretion) was positive in control rats (+47 μmol/d), whereas it was negative in rats fed GUAR (−20 μmol/d), which could involve a higher rate of endogenous cholesterol synthesis. In rats fed PHGG, the steroid balance remained slightly positive. Liver 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was very low (22 pmol/min/mg protein), owing to cholesterol supplementation, in control rats or in rats fed PHGG, whereas it was markedly higher (+463%) in rats fed GUAR. In conclusion, even if PHGG does alter some parameters of the enterohepatic cycle of cholesterol and bile acids, its effects are not sufficient to elicit a significant cholesterol-lowering effect. The intestinal (ileal or cecal) reabsorption of bile acids was not reduced, but rather increased, by GUAR; nevertheless the intestinal capacities of reabsorption were overwhelmed by the enlargement of the digestive pool of bile acids. In the present model, induction of HMG-CoA reductase probably takes place in the presence of elevated portal bile acid concentrations.     

Effectiveness of resistant starch,compared to guar gum,in depressing plasma cholesterol and enhancing fecal steroid excretion

Amylase-resistant starch (RS) represents a substrate that can be administered in substantial amounts in the diet, in contrast to gel-forming polysaccharides, such as guar gum (GG). The aim of this work was thus to compare the effects of GG and RS on cholesterol metabolism in rats adapted to 0.4% cholesterol diets, using dietary GG or RS levels (8 or 20%, respectively) that led to a similar development of fermentations, as assessed by the degree of enlargement of the cecum. The RS diet elicited a marked rise in the cecal pool of short-chain fatty acids, especially acetic and butyric acid, whereas the GG diet favored high-propionic acid fermentations. Both polysaccharides markedly altered the cholesterol excretion, from 50% of ingested cholesterol in controls, up to about 70% in rats adapted to the RS or GG diets. With these diets, the fecal excretion of bile acids was enhanced (67 and 144% with the RS and GG diets, respectively). RS and GG diets were effective in lowering plasma cholesterol (about −40%) and triglycerides (−36%). There was practically no effect of the diets on cholesterol in d>1.040 lipoproteins (high density lipoproteins), whereas RS (and to a larger extent, GG) were very effective to depress cholesterol in d<1.040 lipoproteins (especially in triglyceride-rich lipoproteins). Fermentable polysaccharides counteracted the accumulation of cholesterol in the liver, especially cholesterol esters. In parallel, liver acyl CoA:cholesterol acyltransferase was depressed in rats fed the RS or GG diets, whereas only the GG diet counteracted the downregulation of 3-hydroxy-3-methylglutaryl-CoA by cholesterol. These data suggest that RS may be practically as effective as a gel-forming gum, such as GG, on steroid excretion and on cholesterol metabolism.     

The cholesterol-lowering effect of guar gum in rats is not accompanied by an interruption of bile acid cycling

A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the present model, GG significantly lowered plasma cholesterol (−25%), especially in the density <1.040 kg/L fraction, whereas cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 μmol/d in the control) was shifted toward negative values in rats fed the GG or cholestyramine diets (−27 or −50 μmol/d, respectively). Both agents induced liver 3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied by reduction of bile acid concentration in the large intestine.     

Cholesterol-lowering effects of guar gum: Changes in bile acid pools and intestinal reabsorption

Soluble fibers such as guar gum (GG) may exert cholesterol-lowering effects. It is generally accepted that bile acid (BA) reabsorption in portal blood is reduced, thus limiting the capacity of BA to down-regulate liver cholesterol 7α-hydroxylase, the rate-limiting enzyme of BA synthesis. In the present work, rats were adapted to fiber-free (FF) or 5% GG diets (supplemented or not with 0.25% cholesterol), to investigate various aspects of enterohepatic BA cycling. GG in the diet at a level of 5% elicited a significant lowering of plasma cholesterol during the absorptive period, in cholesterol-free (−13%) or 0.25% cholesterol (−20%) diet conditions. In rats adapted to the GG diets, the small intestinal and cecal BA pools and the ileal vein-artery difference for BA were markedly enhanced; reabsorption in the cecal vein was also enhanced in these rats. [¹⁴C]Taurocholate absorption, determined in perfused ileal segments, was not significantly different in rats adapted to the FF or GG diet, suggesting that a greater flux of BA in the ileum might support a greater ileal BA reabsorption in rats adapted to the GG diet. In contrast, capacities for [¹⁴C]cholate absorption from the cecum at pH 6.5 were higher in rats adapted to the GG diet than to the FF diet. Acidification of the bulk medium in isolated cecum (from pH 7.1 down to pH 6.5 or 5.8) or addition of 100 mM volatile fatty acids was also found to stimulate cecal [¹⁴C]cholate absorption. These factors could contribute to accelerated cecal BA absorption in rats fed the GG diet. The effects of GG on steroid fecal excretion thus appear to accompany a greater intestinal BA absorption and portal flux to the liver. These results suggest that some mechanisms invoked to explain cholesterol-lowering effect of fibers should be reconsidered.     

Dietary α-linolenic acid alters tissue fatty acid composition,but not blood lipids,lipoproteins or coagulation status in humans

We examined the effect of dietary α-linolenic acid (ALA) on the indices of lipid and coagulation status and on the fatty acid composition of serum and peripheral blood mononuclear cell (PBMNC) lipids in ten healthy men (age 21–37 yr) who consumed all their meals at the Western Human Nutrition Research Center for 126 d. There was a stabilization period of 14 d at the start when all 10 subjects consumed the basal diet (BD) containing 23.4 energy percent (en%) fat and two intervention periods of 56 d each. During the first intervention period, 5 subjects consumed the BD containing 23.4 en% fat, and 5 subjects consumed a diet providing 6.3% calories from α-linolenic acid [flaxseed oil (FSO) diet containing 28.8 en% fat]. Diets were crossed over between the two groups during the second intervention period. Feeding the FSO diet did not nignificantly alter serum triglycerides, cholesterol, highdensity lipoproteins, low-density lipoproteins, apoprotein A-I and apoprotein B when compared to the corresponding values in the subjects fed the BD, nor was there any effect of the FSO diet on the bleeding time, prothrombin time and partial prothrombin time for these subjects. Feeding the ALA-containing diet did cause a significant increase in ALA concentration in serum (P<0.001) and PBMNC lipids (P<0.05). It also caused a significant increase (P<0.05) in the eicosapentaenoic and docosapentaenoic acid contents of PBMNC lipids, and a decrease (P<0.01) in linoleic and eicosatrienoic acid contents of serum lipids. Thus, dietary ALA, fed for 56 d at 6.3% of calories, had no effect on plasma triglyceride or very low density lipoprotein levels or the common risk factors associated with atherosclerosis, although these parameters have been reported by others to be influenced by fatty acids, such as palmitic or linoleic acids, in the diet. Dietary ALA did significantly alter the fatty acid composition of plasma and PBMNC. The views expressed in the paper are those of the authors and do not reflect the official policy or position of the Department of Agriculture or Department of Defense, or the U.S. Government.     

Fecal bile acid excretion and composition in response to changes in dietary wheat bran,fat and calcium in the rat

The effect and possible interactive influence of different dietary amounts of wheat bran, fat and calcium on the fecal excretion, concentration and composition of bile acids was studied in Fischer-344 rats. The fecal bile acids were analyzed using gas-liquid chromatography. Dietary wheat bran increased both total bile acid excretion and fecal weight without changes in fecal bile acid concentration. The proportion of fecal hyodeoxycholic acid decreased with increasing dietary fiber, whereas that of lithocholic and deoxycholic acids increased significantly with fiber intake. The percent content of fecal chenodeoxycholic acid did not change. Increasing dietary fat led to an increase in bile acid excretion without changes in either fecal weight or bile acid concentration. In contrast, the level of dietary calcium did not affect the total excretion of bile acids. However, since calcium increased the fecal weight, it consequently diluted bile acids and decreased their fecal concentration. Dietary fat and calcium had no influence on fecal bile acid composition. There were no interactive effects of wheat bran, fat and calcium on fecal bile acids. The finding in this study that dietary fiber, fat and calcium induce significant changes in fecal bile acids may be of relevance to the potential of bile acids to promote carcinogenesis.     

Dietary fat alters the distribution of cholesterol between vesicles and micelles in hamster bile

The type of dietary fat strongly affects the incidence of gallstones in the hamster model of cholesterol cholelithiasis. The present study was designed to determine whether dietary fats could affect gallstone formation by altering the microstructure (vesicular/micellar ratio) of cholesterol in bile. Golden Syrian hamsters from Sasco (Omaha, NE) or Charles River (Wilmington, MA) were fed nutritionally adequate semipurified diets to which were added: (i) 4.0% butterfat without added cholesterol; (ii) 1.2% palmitic acid plus 0.3% cholesterol; or (iii) 4.0% safflower oil plus 0.3% cholesterol. Gallstone incidence and the percentage of cholesterol in vesicles and micelles were determined after two- or six-week feeding periods. Three out of ten Sasco hamsters fed the 1.2% palmitic acid diet for two weeks had cholesterol stones, while none of the eight Charles River animals had stones. In the Sasco hamsters, a significant proportion of the biliary cholesterol was found in void volume vesicles (28.8%) and small vesicles (17.1%); Charles River hamsters had negligible proportions (1.1%) of cholesterol in void volume vesicles and 15.4% in small vesicles. Cholesterol gallstones were most abundant in Sasco hamsters fed 1.2% palmitic acid for six weeks (nine out of ten animals); the mean cholesterol saturation index of the bile was 1.27. A significant proportion of the biliary cholesterol was eluted in the void volume vesicles (21.4%) and in small vesicles (15.0%). Five of the eight identically treated Charles River hamsters had cholesterol stones; the cholesterol saturation index averaged 1.36, and the biliary cholesterol was present in void volume vesicles (31.3%) and small vesicles (14.3%). Vesicles were not detected in the bile of hamsters fed cholesterol-free diets, and none of these animals developed cholesterol gallstones. Safflower oil diets inhibited stone formation even though the cholesterol saturation index was above unity. After six weeks, biliary cholesterol transported in void volume vesicles was highest for Sasco hamsters (13.3%) as compared to Charles River animals (6.9%), but total cholesterol transported in void volume vesicles plus small vesicles was similar in both groups (33.5% vs. 26.2%), respectively. These results suggest that in both strains of hamsters dietary fat influences gallstone formation by modulating the vesicular/micellar distribution of biliary cholesterol. Apparently, the presence of cholesterol/phospholipid vesicles in bile is associated with cholesterol gallstone formation.     

Increased biliary calcium in cholesterol and pigment gallstone disease: The role of altered bile acid composition

The present study was undertaken to define the relationship between calcium metabolism and bile acid composition in animal models of diet induced cholesterol and pigment gallstones. Groups of prairie dogs were fed either a control non-lithogenic chow (N=12), a 1.2% cholesterol enriched chow (N=6, XOL) for two weeks, or a high carbohydrate diet deficient in iron (N=6, CHO-FeD), or a high carbohydrate diet with normal iron levels (N=6, CHO) for eight weeks. Hepatic (HB) and gallbladder (GB) bile samples were analyzed for total calcium, cholesterol, phospholipids, total bile acids (TBA), and individual bile acid composition. In each of the four groups, TBA concentrations were essentially similar and taurine conjugates accounted for approximately 90% of TBA in HB bile and about 98% in GB bile. In the control group, cholic acid (CA) was the predominant bile acid and comprised 76% of TBA and chenodeoxycholic (CDCA) accounted for about 13% of the total. Feeding a diet rich in cholesterol caused a significant change in the relative concentrations of individual bile acids of hepatic bile—such that CA decreased significantly (p<0.001) while CDCA increased by 300% (p<0.001). The changes in secondary bile acids were insignificant. An identical shift in individual bile acid composition was noted in animals maintained on high carbohydrate diet, irrespective of iron content. Similar changes were observed in the GB in the experimental groups. Calcium concentrations of GB bile with or without gallstone formation showed a positive linear relationship with TBA (y=4.35+0.14X, p<0.001) and taurochenodoxycholic acid (TCDCA) (y=15.04+0.46X, p<0.001), but an inverse relationship with taurocholic acid (TCA) (Y=55.16−0.41X, p<0.008). However, such relationships were absent in hepatic bile. These data indicate that diet-induced alterations in bile acid composition may modify calcium solubility or GB function, thereby contributing to the increased GB calcium observed during cholesterol and pigment gallstone formation.     

Fatty acid and sterol composition of ungerminated spores of the vesicular-arbuscular mycorrhizal fungus,Acaulospora laevis

The fatty acids and sterols of ungerminated chlamydospores of the vesicular-arbuscular (VA) endophyteAcaulospora laevis were examined by gas chromatography and mass spectrometry. The total lipid content of the spores was 45.5% of the spore dry weight. Predominant fatty acids were palmitoleic (52.5%), palmitic (25.5%) and oleic (7.4%). Minor fatty acids consisted of a range of (n−3) and (n−6) polyunsaturated acids. The occurrence of (n−3) polyunsaturated fatty acids is rare in fungi of the order Mucorales. Three sterols were identified as 24-ethylcholesterol (79.9%), cholesterol (11.0%) and 24-methylcholesterol (9.2%). No ergosterol was detected. Lipids of the chlamydospores ofA. laevis are compared with those ofGlomus caledonius.     

The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans

Normal healthy male volunteers (n=10) were fed diets (high-AA) containing 1.7 g/d of arachidonic acid (AA) for 50 d. The control (low-AA) diet contained 210 mg/d of AA. Dietary AA had no statistically significant effect on the blood cholesterol levels, lipoprotein distribution, or apoprotein levels. Adipose tissue fatty acid composition was not influenced by AA feeding. The plasma total fatty acid composition was markedly enriched in AA after 50 d (P<0.005). The fatty acid composition of plasma lipid fractions, cholesterol esters, triglycerides, free fatty acids, and phospholipid (PL) showed marked differences in the degree of enrichment in AA. The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3% AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0% AA. The level of 22:4n-6 also was different (0.67 to 1.06%) in the plasma PL fraction after 50 d of AA feeding. After consuming the high-AA diet, the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid. These results indicate that dietary AA is incorporated into tissue lipids, but selectively into different tissues and lipid classes. Perhaps more importantly, the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding.     

Low-dose eicosapentaenoic or docosahexaenoic acid administration modifies fatty acid composition and does not affect susceptibility to oxidative stress in rat erythrocytes and tissues

In view of the promising future for use of n-3 polyunsaturated fatty acids (PUFA) in the prevention of cancer and cardiovascular diseases, it is necessary to ensure that their consumption does not result in detrimental oxidative effects. The aim of the present work was to test a hypothesis that low doses of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) do not induce harmful modifications of oxidative cell metabolism, as modifications of membrane fatty acid composition occur. Wistar rats received by gavage oleic acid, EPA, or DHA (360 mg/kg body weight/day) for a period of 1 or 4 wk. Fatty acid composition and α-tocopherol content were determined for plasma, red blood cell (RBC) membranes, and liver, kidney, lung, and heart microsomal membranes. Susceptibility to oxidative stress induced by tert-butylhydroperoxide was measured in RBC. EPA treatment increased EPA and docosapentaenoic acid (DPA) content in plasma and in all the membranes studied. DHA treatment mainly increased DHA content. Both treatments decreased arachidonic acid content and n-6/n-3 PUFA ratio in the membranes, without modifying the Unsaturation Index. No changes in tissue α-tocopherol content and in RBC susceptibility to oxidative stress were induced by either EPA or DHA treatment. The data suggest that EPA and DHA treatments can substantially modify membrane fatty acids, with-out increasing susceptibility to oxidative stress, when administered at low doses. This opens the possibility for use of low doses of n-3 PUFA for chemoprevention without risk of detrimental secondary effects.     

Synthesis and characterization of a new guar gum 4‐hydroxybenzoic acid resin and its use for the separation of heavy metal ions in industrial effluents

Hydroxybenzoic acid group has been incorporated onto guar gum by modified Porath's method of functionalization of polysaccharides. The newly synthesized guar gum 4‐hydroxybenzoic acid (GHBA) resin was characterized by Fourier‐transform infrared spectroscopy, elemental analysis, ion‐exchange capacity, column reusability, and physicochemical properties. The distribution coefficient (K_d) values and effect of pH on chelation of these metal ions using batch method were studied. The separations of mixture of Fe²⁺, Zn²⁺, Cu²⁺, Cd²⁺, and Pb²⁺ metal ions on GHBA resin on the basis of their distribution coefficient at various pH were also achieved using column chromatography. The effect of experimental parameters such as pH, treatment time, agitation speed, temperature, adsorbent dose, initial metal ion concentration, and flow rate on the removal of metal ions has been also studied. GHBA resin is effective adsorbents for the removal of different toxic metal ions from aqueous solutions and follows the order: Fe²⁺ > Zn²⁺ > Cu²⁺ > Cd²⁺ > Pb²⁺. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers     

Dietary long-chain PUFA in the form of TAG or phospholipids influence lymph lipoprotein size and composition in piglets

Several sources of long-chain PUFA (LCP) are currently available for infant formula supplementation. These oils differ in their FA composition, the chemical form of the FA esters [TAG or phospholipids (PL)], and presence of other lipid components. These differences may affect LCP absorption, distribution, and metabolic fate after ingestion. The purpose of this study was to evaluate the influence of different chemical forms of dietary LCP on the composition of lymph lipoproteins. Eighteen pigs (5 d old) were bottle-fed different diets for 2 wk: a control diet (C), a diet containing LCP as TAG from tuna and fungal oils (TF-TAG), or a diet containing LCP as PL from egg yolk (E-PL). We measured lipid and FA composition of lymph, main lymph fractions (TAG or PL), and the particle size of lymph lipoproteins. The average diameter of lymph lipoproteins was significantly lower in the E-PL group compared with the control and TF-TAG groups (C: 3902 +/- 384 A; TF-TAG: 3773 +/- 384 A; E-PL: 2370 +/- 185 A). Arachidonic acid and DHA contents in lymph and lymph-TAG were significantly higher in the TF-TAG group compared to the E-PL group (0.50 +/- 0.03 and 0.24 +/- 0.03 g/100 g vs. 0.29 +/- 0.04 and 0.12 +/- 0.03 g/100 g, respectively). The addition to the diet of LCP in the form of TAG or PL affected the size of intestinal lipoproteins and also led to a different distribution of these FA in lymph lipoproteins.     

Fatty acid composition of the sterol ester fraction of human adrenal cortex in Cushing's syndrome and after treatment with aminoglutethimide

The lipid that accumulated in the adrenal cortex of a patient who had been treated with aminoglutethimide has been compared with the lipid in normal human adrenal cortex and identified as esters of cholesterol with fatty acids. While the concentration of free cholesterol was normal, that of esterified cholesterol was three times greater than that in normal controls. Sterols were analyzed by gas chromatography and found to consist almost wholly of cholesterol. The fatty acid composition of the cholesterol esters in adrenal cortex from patients with abnormal steroid secretion rates was determined. An increased proportion of cholesteryl arachidonate (cholesteryl-3β-[allcis]-eicosa-5,8,11,14-tetraenoate) was found in adrenal cortex from patients with decreased steroid secretion rates and a decreased proportion in adrenal cortex from patients with steroid secretion rates raised sufficiently to cause Cushing's Syndrome. Publication no. 1429 of the Cancer Commission of Harvard University.     

Changes in lipid content,fatty acid composition and lipoprotein lipase activity in dry goat omental adipose tissue according to tissue site

Water and lipid contents, fatty acid distribution, and lipoprotein lipase activity were determined in 11 samples taken from theOmentum Majus of five dry Alpine goats. Samples were chosen to standardize sampling sites using geometric guide marks representative of different adipose tissue sites. Sample location explained between 20% and 30% of the total variance in water and lipid contents and in lipoprotein lipase activity, and from 5.5% to 45.4% of the total variance in fatty acid distribution. Increased sample thickness was associated with an increase in lipid content and in saturated fatty acid percentages. Samples taken in proximity of the omentum tissue attached to the rumen and abomasum had the highest content. We furthermore found that the levels of 18∶2n−6, 18∶1n−7, and of branched chain fatty acids were high close to a pila of the rumen which also corresponded to high lipoprotein lipase activity. Concomitant high levels of 16∶1n−7, 17∶1n−8, and 18∶1n−9 may reflect high levels of Δ9 desaturase activity.     

Fatty acid composition of tissue phospholipids and prostaglandin excretion in hyperlipidemia induced in rats by implantation of the mammotropic pituitary tumor MtT-F4

A mammotropic pituitary tumor, MtT-F4, was implanted into male Fisher 344 rats for a period of 4 weeks. This tumor induced growth retardation, hyperlipidemia, hepatic hypertrophy and adrenal hyperplasia. Lipids were extracted from various tissues. In tumor-bearing rats, phospholipid concentration was found to be increased in plasma, spleen and testis. Distribution among the various phospholipid classes was similar to that of controls except in liver and heart, where phosphatidylcholine was increased at the expense of phosphatidylinositol and phosphatidylserine. The main difference was in the fatty acid composition of major phospholipids. The proportion of omega 6 fatty acids was lower and that of docosahexaenoic acid of the omega 3 series (22:6 omega 3) was higher in most tissues, especially in plasma, liver, heart and kidney. Concurrently, the urinary excretion of two endogenous metabolites of PGI2 (2,3-dinor-6-keto-PGF1 alpha and 6,15-diketo-13,14-dihydro-2,3-dinor-PGF1 alpha) was found to be increased significantly in tumor-bearing rats. The results raise the hypothesis that hormonal changes induced by the MtT-F4 tumor accelerate the conversion of arachidonic acid (20:4 omega 6) to prostaglandins. This effect, perhaps coupled with a diversion of linoleic acid (18:2 omega 6) towards other metabolic processes, would account for a partial depletion of membrane phospholipids in 18:2 omega 6 and for the reduced production of longer chain omega 6 unsaturated acids from 20:4 omega 6, creating a state of "relative essential fatty acid deficiency." As a result, the metabolism of omega 3 fatty acids is altered towards an enhanced production of 22:6 omega 3 which accumulates in the lipids of cell membranes to compensate for the depletion of unsaturated acids of the omega 6 series.     

Cholesterol synthesis in the vertebrate retina: Effects of U18666A on rat retinal structure, photoreceptor membrane assembly, and sterol metabolism and composition

Treatment of neonatal rats with U18666A, an inhibitor of desmosterol Δ²⁴-reductase, results in accumulation of desmosterol (Δ^5,24) and depletion of cholesterol (Δ⁵) in various bodily tissues and also causes cataracts. We evaluated the effects of U18666A on the sterol composition, de novo sterol synthesis, and histological structure of the retina. Neonatal Sprague-Dawley rats were injected subcutaneously with U18666A (15 mg/kg, in olive oil) every other day from birth through 3 wk of age; in parallel, control rats received olive oil alone. At 21 d, treated and control groups each were subdivided into two groups: one group of each was injected intravitreally with [³H]acetate; retinas were removed 20 h later and non-saponifiable lipids (NSL) were analyzed by radio-high-performance liquid chromatography. The other group was injected intravitreally with [³H]leucine; 4 d later, one eye of each animal was evaluated by light and electron microscopy and light microscopic autoradiography, while contralateral retinas and rod outer segment (ROS) membranes prepared thereform were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/fluorography. In the treated group, the Δ⁵/Δ^5,24 mole ratio of retinas was ca. 1.0, and >88% of the NSL radioactivity was in Δ^5,24; in contrast, control retinas had Δ⁵/Δ^5,24 >170, with >80% of the NSL radioactivity in Δ⁵. Retinal histology, ultrastructure, ROS renewal rates, and rhodopsin synthesis and intracellular trafficking were comparable in both treated and control animals. These results suggest that desmosterol can either substitute functionally for cholesterol in the retina or it can complement subthreshold levels of cholesterol by sterol synergism.     

Seasonal changes in lipid and fatty acid composition of the freshwater mollusk,Diplodom patagonicus

Diplodom patagonicus is a freshwater bivalve mollusk living in lakes of the patagonian Andes mountains in Argentina. Lipid composition and seasonal changes in the mollusk were studied in the natural habitat. In addition to common nonpolar and polar lipids, small amounts of alk-1-enyldiacylglycerol ethers and significant quantities of ceramide aminoethyl phosphonate were present. Total lipid content changed during the year, primarily because of decreased triacylglycerols in winter. The fatty acid composition of the lipids, remarkably different from that of marine bivalves, and even from other fresh water animals, was especially rich in the ω6 fatty acids, linoleic and arachidonic (ca. 25%), and poor in the ω3 acids, 20∶5 and 22∶6. The ω6/ω3 acid ratio was ca. 2, which is very high compared to marine bivalves. The fatty acid composition and the ω6/ω3 acid ratio were constant during the whole year, suggesting a very stable diet, rich in vegetal detritus and poor in diatoms. The influence of environmental temperature fluctuation with season on fatty acid composition also was negible. Modest proportions of 22∶2 nonmethylene-interrupted (NMI) acids were detected and confirmed by mass spectrometry. It was shown that 20∶2 NMI acids were absent.     

Kinetics of absorption,equilibration (or distribution), and excretion of orally and intraperitoneally administered cholesterol in the rat

Resorption and metabolism of cholesterol administered intraperitoneally and per os have been described in the rat utilizing a technique of double isotopic labeling. Depending upon the route of administration, these parameters vary to a large degree. Alimentary cholesterol is progressively resorbed over a period of 10 hr, while the maximal blood level of cholesterol is attained after the 6th hr following intraperitoneal injection. On the other hand, cholesterol administered per os is more rapidly utilized in biliary acid synthesis than cholesterol administered intraperitoneally. In the range of concentrations utilized in this work (10–300 μg and 0.2–300 μg, respectively, administered to the rat, orally and intraperitoneally), the rate of cholesterol resorption remained constant.