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M L Fernandez

Publications and source records attributed to M L Fernandez.

At least 55 records · Page 3Linked to original sources

Dietary fat saturation and chain length modulate guinea pig hepatic cholesterol metabolism.

The effects of dietary fat saturation and saturated fatty acid composition on plasma lipoprotein concentrations and hepatic cholesterol metabolism were investigated in guinea pigs. Animals were fed semipurified diets containing 15 g fat/100 g diet, as palm kernel, palm oil, beef tallow, lard, olive oil or corn oil. Plasma lipoprotein concentrations were significantly altered by the type of dietary fat. The LDL cholesterol concentration was highest in animals fed the diet with palm kernel and lowest in animals fed the diet with corn oil, whereas HDL cholesterol was lowest in beef tallow-fed guinea pigs (P < 0.01). Hepatic cholesteryl ester concentrations were 100% higher in animals fed diets containing polyunsaturated corn oil and monounsaturated olive oil compared with animals fed any of the saturated fat diets (P < 0.01). Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity varied in the different dietary fat groups independent of hepatic cholesterol pools or plasma LDL concentrations. In contrast, hepatic acyl-CoA: cholesterol acyltransferase (ACAT) activity was significantly correlated with plasma LDL cholesterol across all dietary groups (r = 0.63, P < 0.001). These data demonstrate that regulation of hepatic HMG-CoA reductase activity is relatively independent of changes in plasma lipoprotein levels, whereas hepatic ACAT activity exhibits a positive correlation with plasma LDL cholesterol concentrations.

Animal Nutritional Physiological Phenomena↗

Prickly pear (Opuntia sp.) pectin alters hepatic cholesterol metabolism without affecting cholesterol absorption in guinea pigs fed a hypercholesterolemic diet.

Prickly pear pectin intake decreases plasma LDL concentrations by increasing hepatic apolipoprotein B/E receptor expression in guinea pigs fed a hypercholesterolemic diet. To investigate whether prickly pear pectin has an effect on cholesterol absorption and on enzymes responsible for hepatic cholesterol homeostasis, guinea pigs were fed one of three semipurified diets, each containing 15 g lard/100 g diet: 1) the lard-basal diet with no added cholesterol or prickly pear pectin (LB diet); 2) the LB diet with 0.25 g added cholesterol/100 g diet (LC diet); or 3) the LC diet containing 2.5 g prickly pear pectin/100 g diet, added at the expense of cellulose (LC-P diet). Animals fed the LB diet had the lowest plasma LDL and hepatic cholesterol concentrations, followed by animals fed the LC-P diet (P < 0.001). Hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was highest in the group fed the LB diet, with similar values for animals in the other two groups. A positive correlation existed between plasma LDL cholesterol concentration and hepatic acyl CoA:cholesterol acyltransferase activity (r = 0.87, P < 0.001). Cholesterol absorption was not different among the three dietary groups. These results indicate that the decreased plasma and hepatic cholesterol concentrations of animals fed prickly pear pectin are not explained by differences in cholesterol absorption but rather are due to mechanisms that alter hepatic cholesterol homeostasis, resulting in lower plasma LDL concentrations.

Animals↗

Regulation of hepatic LDL metabolism in the guinea pig by dietary fat and cholesterol.

Studies were carried out to determine the independent and interactive effects of dietary fat and cholesterol on the regulation of hepatic apoB/E receptor expression and its relationship to hepatic cholesterol concentrations and low density lipoprotein (LDL) particle characteristics. Guinea pigs were fed 15% (w/w) fat diets (lard, olive oil, or corn oil) with cholesterol levels corresponding to absorbed intakes of 6 (basal), 50, 100, or 200% endogenous cholesterol synthesis. Guinea pigs maintained stable plasma cholesterol levels until cholesterol intake equaled or exceeded endogenous synthesis (P < 0.001). Fat type independently affected plasma total and LDL cholesterol levels such that lard > corn oil, with olive oil being intermediate (P < 0.05). Hepatic membrane apoB/E receptor number (Bmax) decreased as dietary cholesterol increased (P < 0.001) without an independent effect of dietary fat saturation. Bmax values were significantly correlated with plasma LDL cholesterol levels (r = -0.632), and with hepatic free (r = 0.527) and esterified cholesterol (r = -0.512) concentrations, which were both increased with dietary cholesterol (P < 0.001). Significant interactions between dietary fat type and cholesterol mediated the extent of hepatic free and esterified cholesterol accumulation. Dietary fat and cholesterol interactions also contributed to changes in LDL particle composition and peak density. The results of these studies do not support the thesis that dietary cholesterol-mediated suppression of apoB/E receptor expression is ameliorated by intake of polyunsaturated fatty acids. Dietary fat type and cholesterol amount interactively affect hepatic cholesterol concentrations and LDL composition and size, which in part determine plasma LDL cholesterol levels.

Animals↗

Dietary fat saturation modifies the metabolism of LDL subfractions in guinea pigs.

The effects of dietary fat saturation on the metabolism of low-density lipoprotein (LDL) subfractions were measured in adult male guinea pigs fed semipurified diets containing 15% (wt/wt) corn oil (CO; 58% linoleic acid), lard (24% palmitic/14% stearic acid), or palm kernel oil (PK; 52% lauric/18% myristic acid). Animals fed the CO diet had lower plasma total cholesterol levels than guinea pigs fed the PK or lard diets (P < .01). Plasma LDL-1 (d = 1.019 to 1.05 g/mL) concentrations were 3.5- and 2.4-fold higher in animals fed the PK diet compared with the CO and lard groups, respectively, while LDL-2 (d = 1.05 to 1.09 g/mL) concentrations were not different among groups. For all dietary fat groups LDL-1 had a higher molecular weight and a larger diameter than LDL-2. LDL fractional catabolic rates (FCRs) varied, depending on both the diet and the LDL subfraction. Animals fed the polyunsaturated CO diet had a more rapid LDL FCR than animals from the other two groups (P < .01). Within the same diet group, LDL-2 exhibited a slower turnover rate than LDL-1 in animals fed the PK diet, while no differences in LDL subfraction FCR were found in the CO and lard groups. Animals fed the PK and lard diets did not exhibit significant modifications in the density distribution of LDL subfractions over a period of 33 hours. In contrast, animals fed the CO diet exhibited a shift of more buoyant to denser LDL particles, suggesting that differences in LDL intravascular processing are mediated by dietary fat saturation. In vitro LDL binding to hepatic membranes confirmed the in vivo data with an increased expression of apolipoprotein B/E receptors (Bmax) in animals fed the CO diet (P < .01). Hepatic apolipoprotein B/E receptors exhibited less affinity for LDL-2 in the PK group, a result consistent with the less rapid turnover of LDL-2 in PK-fed animals. The results suggest that dietary fatty acids varying in saturation and composition have distinctive atherogenic potentials. The lowest plasma LDL cholesterol concentrations mediated by CO intake could in part be explained by induced changes in the composition and processing of LDL subfractions, resulting in faster LDL turnover rates in addition to increased expression of hepatic apolipoprotein B/E receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Dietary fat type and cholesterol quantity interact to affect cholesterol metabolism in guinea pigs.

Interactions of dietary fat saturation with dietary cholesterol on cholesterol homeostasis in guinea pigs were studied by feeding 15% (wt/wt) fat diets containing lard, olive oil or corn oil, with 0.00, 0.08, 0.17 or 0.33% added cholesterol. Plasma total and LDL cholesterol concentrations significantly increased with increasing dietary cholesterol, with pronounced increments occurring at the pharmacologic (0.33%) level. An interaction between fat type and dietary cholesterol was seen for HDL cholesterol concentrations. Saturated fat and the pharmacologic level of dietary cholesterol increased plasma HDL concentrations, whereas polyunsaturated fat minimized the dietary cholesterol-mediated increase. Interactions were also observed for hepatic cholesterol: dietary cholesterol increased both free and esterified hepatic cholesterol concentrations in all groups fed all the dietary fats, and fat type influenced the extent of hepatic cholesterol accumulation. Lard-fed animals accumulated the least hepatic cholesterol over the range of dietary cholesterol intakes. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, with maximal suppression at all levels of cholesterol intake. Dietary cholesterol had a greater effect on plasma and hepatic cholesterol concentrations and hepatic HMG-CoA reductase activity than did fat type. The data indicated limited interactions of fat type and cholesterol quantity in altering mechanisms regulating plasma cholesterol homeostasis.

Acyl Coenzyme A↗

Prickly pear (Opuntia sp.) pectin reverses low density lipoprotein receptor suppression induced by a hypercholesterolemic diet in guinea pigs.

The effects of prickly pear pectin on plasma LDL metabolism were investigated by feeding guinea pigs either a diet containing 15 g/100 g lard and 0.25 g/100 g cholesterol (LC diet) or the LC diet in which cellulose was partially replaced (2.5 g/100 g) by prickly pear pectin (LC-P diet). The LC-P diet lowered plasma LDL cholesterol concentrations by 33% (P < 0.001). Low density lipoprotein composition was modified by intake of prickly pear pectin; the relative percentages of free and esterified cholesterol were lower and triglycerides were higher in LDL from animals fed the LC-P diet (P < 0.05). Intake of prickly pear pectin did not affect hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity; however, hepatic free and esterified cholesterol concentrations were lowered by 46 and 64%, respectively. Hepatic apolipoprotein B/E receptor expression (Bmax) was 60% higher in animals fed the LC-P diet (P < 0.01). Similar to the in vitro data, receptor-mediated LDL fractional catabolic rates were 190% higher in animals fed the LC-P diet (P < 0.05), whereas apolipoprotein LDL flux rates were not affected. Apolipoprotein LDL pool size and fractional catabolic rates exhibited a significant correlation (r = -0.52, P < 0.01). These data indicate that an increase in apolipoprotein B/E receptor expression is a major metabolic response by which intake of prickly pear pectin decreases plasma LDL concentrations.

Animals↗

Regulation of guinea pig plasma low density lipoprotein kinetics by dietary fat saturation.

Dietary fat saturation has been shown to affect hepatic apoB/E receptor expression and to modify low density lipoprotein (LDL) composition and density in guinea pigs. The current studies were designed to investigate the independent and interactive effects of dietary fat saturation alterations in apoB/E receptor expression and LDL composition on in vivo LDL turnover kinetics, both receptor-mediated and receptor-independent. Guinea pigs were fed semi-purified diets containing 15% fat, either polyunsaturated corn oil (CO), monounsaturated olive oil (OL), or saturated lard, and injected with radioiodinated LDL isolated from animals fed the homologous diet. Blood samples were obtained over 33 h to determine apoLDL fractional catabolic rates (FCR) and flux rates. Compared to animals fed OL- or lard-based diets, intake of the CO-based diet resulted in a 50% decrease in LDL apoB pool size associated with a twofold increase in receptor-mediated FCR (P less than 0.001) and a 28% decrease in flux rate (P less than 0.05). Maximal LDL binding capacity of hepatic apoB/E receptors, determined in vitro, was twofold higher for animals fed the CO-based diet compared to guinea pigs fed the OL- and lard-based diets (P less than 0.01). There was a significant correlation between hepatic apoB/E receptor number and in vivo receptor-mediated LDL FCR (r = 0.987). Significant differences in LDL turnover were related to the source of LDL. When injected into animals fed a nonpurified commercial diet, the smaller, cholesteryl ester-depleted LDL isolated from animals fed the CO-based diet had a twofold higher FCR compared to larger LDLs from guinea pigs fed the OL- and lard-based diets, which had similar turnover rates. When LDL from animals fed the commercial diet was radiolabeled and injected into animals fed the three types of dietary fat, significant differences in LDL turnover were observed in the order CO greater than lard greater than OL, suggesting that intravascular processing and tissue uptake of the smaller LDL from animals fed the commercial diet varies depending on the dietary fat saturation fed to the recipient animals. These studies demonstrate that guinea pigs fed polyunsaturated fat diets lower plasma LDL levels in part by an increase in apoB/E receptor-mediated fractional LDL turnover and a decrease in apoLDL flux. In addition, fat saturation alters LDL composition and size which independently affect LDL turnover rates in vivo.

Animals↗

Differential effects of saturated fatty acids on low density lipoprotein metabolism in the guinea pig.

Studies have shown that dietary fat saturation affects guinea pig plasma low density lipoprotein (LDL) levels by altering both LDL receptor-mediated catabolism and flux rates of LDL (Fernandez et al. 1992. J. Lipid Res. 33: 97-109). The present studies investigated whether saturated fatty acids of varying chain lengths have differential effects on LDL metabolism. Guinea pigs were fed 15% (w/w, 35% calories) fat diets containing either palm kernel oil (PK), 52% lauric acid/18% myristic acid; palm oil (PO), 43% palmitic acid/4% stearic acid; or beef tallow (BT), 23% palmitic acid/14% stearic acid. Plasma LDL cholesterol levels were significantly higher for animals fed the PK diet (P < 0.001) with values of 83 +/- 19 (n = 12), 53 +/- 8 (n = 12) and 44 +/- 16 (n = 10) mg/dl for PK, PO, and BT diets, respectively. The relative percentage composition of LDL was modified by fat type; however, LDL diameters and peak densities were not different between diets, indicating no effect of saturated fatty acid composition on LDL size. ApoB/E receptor-mediated LDL fractional catabolic rates (FCR) were significantly lower in animals fed the PK diet (P < 0.01) and LDL apoB flux rates were reduced (P < 0.01) in animals fed the BT diet. A correlation was found between plasma LDL levels and receptor-mediated LDL catabolism (r = -0.66, P < 0.01). A higher apoB/E receptor number (Bmax), determined by in vitro LDL binding to guinea pig hepatic membranes, was observed for animals fed BT versus PK or PO diets and Bmax values were significantly correlated with plasma LDL levels (r = -0.776, P < 0.001). These results indicate that saturated fatty acids of varying chain length have differential effects on hepatic apoB/E receptor expression and on LDL apoB flux rates which in part account for differences in plasma LDL cholesterol levels of guinea pigs fed these saturated fats.

Animals↗

Characterization of high-density lipoprotein binding to guinea pig hepatic membranes: effects of dietary fat quality and cholesterol feeding.

The effects of dietary fat quality and cholesterol intake on expression of guinea pig hepatic membrane high-density lipoprotein (HDL) binding sites were studied. Animals were fed semisynthetic diets containing 7.5% (wt/wt) of either corn oil (CO), olive oil (OL), or lard. The cholesterol diet was prepared by incorporating 0.25% recrystallized cholesterol into standard guinea pig chow. Plasma cholesterol levels of guinea pigs on the CO diet were significantly lower (P less than .02) than animals on the OL or lard diets. HDL cholesterol levels did not differ between the polyunsaturated, monounsaturated, and saturated dietary fat groups. Guinea pigs on the high cholesterol diet had increased total and HDL cholesterol levels compared with animals on the chow diet (P less than .01). Initial studies demonstrated that HDL binding to hepatic membranes was temperature-dependent. A threefold increase in binding was observed when assays were performed at 37 degrees C, as compared with 4 degrees C, for all membrane preparations. Dietary fat quality and dietary cholesterol intake significantly altered HDL binding to hepatic membranes with increased HDL binding to membranes of animals fed polyunsaturated fat and the high cholesterol diet. At 37 degrees C, HDL binding to hepatic membranes of CO-fed animals was 26% and 46% higher than for membranes of OL- and lard-fed guinea pigs, respectively. A high cholesterol intake increased HDL binding by 24% at both 4 degrees C and 37 degrees C. Scatchard analysis demonstrated that while membrane affinity for HDL (Kd) was not affected by diet, changes did occur in the total number of HDL binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of cholesterol and lipoprotein metabolism in guinea pigs mediated by dietary fat quality and quantity.

The effects of dietary fat quality and quantity on regulation of cholesterol and lipoprotein metabolism were measured in guinea pigs. The animals were fed 7.5 or 15% (wt/wt) fat diets containing either polyunsaturated corn oil (CO), monounsaturated olive oil (OL) or saturated lard as the fat source. Dietary fat quality had a number of significant effects: animals fed the CO-based diet had lower plasma LDL levels and LDL particles of higher density with decreased ratios of core-to-surface components. Apoprotein B/E receptor-mediated binding of LDL to hepatic membranes was twofold higher for animals fed the CO-based diet. Animals fed the OL-based diet had lower hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity and increased levels of hepatic cholesterol. Hepatic cholesteryl ester levels were lowest for animals fed the lard-based diet. Increasing dietary fat quantity resulted in increased plasma LDL levels and hepatic cholesterol, HMG-CoA reductase activity and receptor affinity for LDL. No changes were observed in LDL binding. These data demonstrate that, independent of dietary fat quantity, CO-based diets lower plasma LDL levels, modify LDL composition and increase hepatic apoprotein B/E receptor number.

Administration, Oral↗

Tolerance to nitrendipine in patients with arterial hypertension accompanying chronic renal failure.

To test the tolerance to nitrendipine in arterial hypertension secondary to chronic renal parenchymatous disease, a group of 10 patients so diagnosed and adequately controlled with a diuretic alone or with a beta-blocker were switched to nitrendipine at a dose to insure similarly adequate control of blood pressure. Patients were followed for 1 year at monthly intervals during which blood pressure measurement and the determination of a biochemical profile were performed. During the follow-up, nitrendipine adequately controlled blood pressure and a significant fall was observed in hematocrit (p less than 0.05) and serum uric acid (p less than 0.01) values. Meanwhile, the glomerular filtration rate, determined by the creatinine clearance, did not exhibit significant changes nor did the 24-h urinary excretion of proteins. The tolerance of the drug was adequate, with two patients presenting minimal ankle edema. These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension secondary to chronic renal parenchymatous disease.

Adult↗

Whole body and hepatic cholesterol synthesis rates in the guinea-pig: effect of dietary fat quality.

The effects of polyunsaturated, monounsaturated and saturated dietary fat on total and hepatic cholesterol synthesis were studied in the guinea-pig. Male Hartley guinea-pigs were fed semi-synthetic diets containing 7.5% (w/w) of either corn oil (CO), olive oil (OL) or lard for a period of 5 weeks and rates of endogenous cholesterol synthesis were determined from the incorporation of [3H]water into digitonin-precipitable sterols (DPS) and by measurement of sterol balance. In addition, total and expressed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities were determined in hepatic microsomes. Rates of whole body cholesterol synthesis determined by incorporation of [3H]water into DPS were significantly lower for guinea-pigs on the CO diet with values of 18.7 +/- 1.8 mumol/h (n = 4) vs. 26.7 +/- 4.8 and 24.6 +/- 1.8 mumol/h for animals on the OL (n = 4) and lard (n = 3) diets (P less than 0.001), respectively. Hepatic cholesterol synthesis rates were significantly decreased in animals on the OL diet, whether determined from incorporation of [3H]water into DPS or by analysis of HMG-CoA reductase activity. Hepatic total and free cholesterol levels were not different for animals on the three dietary fats; however, cholesteryl ester levels were 35% lower in guinea-pigs fed the lard diet (P less than 0.02). Sterol balance measurements indicated that whole body cholesterol synthesis rates were not affected by dietary fat quality (51.9 +/- 12.2, 42.8 +/- 7.6 and 51.2 +/- 20.2 mg/kg per day for animals on the CO, OL and lard diets, respectively). This is in striking contrast to the observed reduction in cholesterol synthesis rates for animals on the polyunsaturated CO diet as determined by incorporation of [3H]water into DPS. One possible explanation for the discrepancy between the sterol balance and [3H]water incorporation data is a polyunsaturated fat-mediated effect on energy utilization, which affects the equilibration of NADPH with the body water pool such that the [3H]NADPH has a lower specific activity than body [3H]water.

Animals↗

High-density lipoprotein binding to guinea-pig hepatic membranes. Comparison of guinea-pig and human ligands.

Human and guinea-pig apo-E-free HDL were incubated with isolated guinea-pig hepatic membranes at 4 and 37 degrees C to determine the effects of temperature and heterologous systems on the equilibrium parameters of HDL binding. Receptor mediated HDL binding was highest at 37 degrees C for both lipoproteins. At 4 degrees C, a higher affinity constant (Kd) was observed when guinea-pig HDL was the ligand relative to human HDL; in contrast, both HDL preparations had similar Kd values at 37 degrees C. Calculated binding and receptor number (Bmax) were higher at both temperatures when guinea-pig HDL was the ligand. These results demonstrate a significant species difference in HDL binding to hepatic membrane which is partially temperature-dependent.

Animals↗

Pectin isolated from prickly pear (Opuntia sp.) modifies low density lipoprotein metabolism in cholesterol-fed guinea pigs.

The effect of prickly pear soluble fiber on low density lipoprotein (LDL) metabolism was investigated by feeding male guinea pigs either a nonpurified diet containing 0.25% cholesterol (HC diet) or the HC diet + 1% prickly pear pectin (HC-P diet). Plasma cholesterol levels were significantly decreased by the HC-P diet, with a 33% decrease in LDL levels (p less than 0.02) and an increase in LDL density. Hepatic free and esterified cholesterol levels were reduced 40 and 85%, respectively (p less than 0.002), by the HC-P diet. Hepatic microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase levels were not different. 125I-LDL binding to hepatic membranes was increased 1.7-fold by the HC-P diet (p less than 0.001), with receptor affinity (Kd) being unaltered and receptor number (Bmax) being significantly increased (p less than 0.001). These data suggest that prickly pear pectin may act by a mechanism similar to that of bile acid-binding resins in lowering plasma cholesterol levels. The observed reduction in LDL and hepatic cholesterol levels and increase in LDL density and hepatic apolipoprotein B/E receptors are responses suggesting an increased demand on hepatic cholesterol from increased excretion of bile acids and interruption of the enterohepatic circulation.

Administration, Oral↗

Dietary fat-mediated changes in hepatic apoprotein B/E receptor in the guinea pig: effect of polyunsaturated, monounsaturated, and saturated fat.

These studies investigated the effects of dietary fat quality on guinea pig plasma total and low-density lipoprotein (LDL) cholesterol and triglyceride levels; LDL composition, density, and binding affinity to hepatic apolipoprotein (apo) B/E receptors; and hepatic apo B/E receptor levels. Animals were fed semi-synthetic diets containing 7.5% (weight per weight) fat--either corn oil (CO), olive oil (OL), or lard. Plasma cholesterol levels were significantly lower on the CO diet compared with the OL and lard diets. The isolated LDL had mean peak densities that ranged from 1.071 for LDL from lard-fed animals to 1.075 for LDL from CO- and OL-fed animals. The cholesterol ester to protein ratio of the LDL particle decreased in CO-fed guinea pigs. Binding studies showed that these compositional changes of the LDL had no effect on the binding affinity of the particles to a standardized hepatic membrane preparation. Membrane phospholipid fatty acid compositions were significantly different among the three dietary fat groups. When hepatic membranes were incubated with 125I-labeled LDL, the receptor-mediated binding of LDL to membranes from CO-fed animals increased 1.5-fold compared with binding to membranes from OL- and lard-fed guinea pigs. Scatchard plots indicated an increase of 50% in receptor number in membranes of animals fed the CO diet, whereas the affinity of the hepatic apo B/E receptor for LDL (Kd) was virtually identical for all membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nutritional evaluation of chickpea and germinated chickpea flours.

The ability of seed germination to increase the nutritional quality of chickpea was studied. Chickpea flours germinated for 0, 24 and 48 h were evaluated nutritionally by determination of protein efficiency ratio (PER), net protein ratio (NPR), digestibility and essential amino acid availability "in vivo". A significant increase in ascorbic acid was observed during germination. PER and NPR values indicated that germinated chickpea flours compared favorably to casein. Protein digestibility decreased as germination time increased. Essential amino acid availability did not change after 24 h of germination, but a small decrease was observed after 48 h. The increase in some amino acids during germination may account for the observed increase in PER for the germinated flours. Seed germination enhanced significantly the nutritional quality of chickpea protein and substantially increased the ascorbic acid level.

Amino Acids↗

Corn husk oil lowers plasma LDL cholesterol concentrations by decreasing cholesterol absorption and altering hepatic cholesterol metabolism in guinea pigs.

To test the hypocholesterolemic mechanisms of corn husk oil (CoHO), male Hartley guinea pigs were fed diets containing increasing doses of CoHO, either 0 (control), 5, 10, or 15 g/100 g, and 0.25 g/100 g cholesterol. A positive control group (LC) with low dietary cholesterol (0.04 g/100 g) was also included. Fat was adjusted to 15 g/100 g in all diets by the addition of regular corn oil. Plasma low density lipoprotein (LDL) cholesterol concentrations were 32, 55, and 57% (P < 0.0005) lower with increasing doses of CoHO. In addition, intake of CoHO resulted in 32 to 43% lower hepatic total and esterified cholesterol and 55 to 60% lower triacylglycerol concentrations compared with the control group (P < 0.01). CoHO intake resulted in plasma and hepatic cholesterol concentrations similar to those in guinea pigs from the LC group. The number of cholesteryl ester and free cholesterol molecules was higher in LDL from the control group than in LDL from the CoHO or the LC groups. Hepatic beta-hydroxy-beta-methylglutaryl-coenzyme A reductase activity was not modified by CoHO intake whereas cholesterol 7alpha-hydroxylase was up-regulated by 45 to 49% (P < 0.01) in the 10 and 15 g/100 g CoHO groups. Hepatic acyl coenzyme A cholesterol acyltransferase activity was down-regulated in a dose-dependent manner by 54, 58, and 63% with increasing doses of CoHO. CoHO intake resulted in increased fecal cholesterol excretion by 40 to 55% compared with the control and LC groups. Total fecal neutral sterol excretion was enhanced 42 to 55% by CoHO compared with the control group and by 59 to 68% compared with the LC group. The data from these studies suggest that CoHO has its hypocholesterolemic effect by decreasing cholesterol absorption and increasing bile acid output. These alterations in the intestinal lumen alter hepatic cholesterol metabolism and may affect the synthesis and catabolism of lipoproteins.

Journal Article↗