Biomedical subjects

M L Fernandez

Publications and source records attributed to M L Fernandez.

At least 37 records · Page 2Linked to original sources

PubMed1998

Correlations between intestinal parasitosis, physical growth, and psychomotor development among infants and children from rural Nicaragua.

The correlations between malnutrition, parasitosis (especially helminth infections), and child development are complex, and studies of these interrelationships will allow health agencies to maximize screening and intervention strategies for developing countries. We examined these correlations in a cross-sectional program in Carazo State, Nicaragua. Nine hundred sixty-one children in two age strata (ages 0-24 months and ages 2-10 years) from one urban and three rural communities were screened for intestinal parasites (direct smear and ZnSO4 flotation), malnutrition, and developmental delays. Nutritional status was determined as weight-for-age (WFA), weight-for-height (WFH), and height-for-age (HFA). Developmental status (normal, suspect) was determined for the four subtests of the Denver II Screening Test. The prevalence of malnutrition was 14.6% (WFA), 8.4% (WFH), and 36.3% (HFA). Parasitosis was more prevalent in children less than 24 months of age with low HFA, whereas in older children low WFA was more closely associated with parasitic infections. Ascaris and Trichuris were more prevalent in malnourished children. On the Denver II, suspect test results in all four categories (language, social, gross motor, and fine motor) were associated with low WFA, and suspect language tests were associated with both intestinal parasites (P = 0.0003) and Ascaris infection in particular (P = 0.044). Developmental disabilities are a significant and frequently undetected health problem in developing countries, and malnutrition associated with intestinal helminth infections may be an important contributory factor for these disabilities.

Body Height↗

PubMed1998

Hypolipidemic mechanisms of pectin and psyllium in guinea pigs fed high fat-sucrose diets: alterations on hepatic cholesterol metabolism.

Studies were conducted to determine whether pectin (PE) or psyllium (PSY) could reverse the high plasma cholesterol and triacylglycerol (TAG) concentrations induced by high fat (HF) or high sucrose (HS) diets and which are the mechanisms involved. Male guinea pigs were fed either a low fat (LF) or a HF diet with 80% of the carbohydrate energy derived from sucrose. Cellulose was used as control. Plasma LDL cholesterol, TAG, apolipoprotein B, and hepatic cholesteryl ester were lower in guinea pigs fed PE and PSY compared to the control group (P < 0.03). In addition, a 45% higher number of hepatic apoB/E receptors was observed by PE and PSY intake. Hepatic ACAT, HMG-CoA reductase, and cholesterol 7alpha-hydroxylase (C7H) activities were higher in the HF compared to the LF groups (P < 0.01). PSY intake with HF resulted in up-regulation of C7H and HMG-CoA reductase activities (P < 0.05). Additional studies measuring the effects of PE and PSY on low density lipoprotein (LDL) transport and very low density lipoprotein (VLDL) secretion were conducted in the HF groups. ApoB secretion was reduced by pectin and psyllium (P < 0.01) intake while LDL fractional catabolic rates were 100% faster in guinea pigs fed PE or PSY. In these studies the extent of the hypolipidemic response was specific to each fiber type and associated with the amount of sucrose. In addition, PSY altered the activity of hepatic enzymes of cholesterol homeostasis in the HF group. These additional effects of PSY might explain the more dramatic changes in plasma lipid levels associated with PSY consumption.

Animals↗

PubMed1997

Regulation of apolipoprotein B-containing lipoproteins by dietary soluble fiber in guinea pigs.

Dietary soluble-fiber sources such as pectin, guar gum, or psyllium decrease plasma concentrations of low-density-lipoprotein (LDL) cholesterol in guinea pigs by distinct mechanisms, including increases in LDL apolipoprotein (apo) B turnover and/or decreases in LDL apo B flux (J Lipid Res 1995; 36:2394-404). The present studies were undertaken to test whether changes in the rates of very-low-density lipoprotein (VLDL) apo B secretion, VLDL conversion to LDL, and hepatic uptake of VLDL were related to the cholesterol-lowering actions of these soluble fibers. Guinea pigs were fed (by wt) 12.5% pectin, 12.5% guar gum, 7.5% psyllium, or a control diet containing cellulose as the fiber source. Plasma cholesterol concentrations were significantly lower in guinea pigs fed pectin, guar gum, and psyllium by 42%, 46%, and 35%, respectively (P < 0.001), compared with those animals fed the control diet, whereas plasma triacylglycerol concentrations were lower only with guar gum intake. The secretion rate of triacylglycerol, determined after Triton was injected to block VLDL catabolism, was not different among dietary treatment groups whereas the secretion rate of apo B was lower with pectin, guar gum, and psyllium intakes (P < 0.01). In addition, pectin, guar gum, and psyllium significantly altered the composition of newly secreted VLDLs by increasing the number of triacylglycerol and phospholipid molecules in the secreted lipoprotein, indicating the presence of larger nascent VLDLs. In contrast, the average particle diameter of mature VLDLs as determined by electron microscopy was smaller in the dietary soluble-fiber groups in the following order: pectin < psyllium < guar gum. Plasma lecithin-cholesteryl acyltransferase and cholesteryl ester transfer protein activities were lower with intake of pectin, guar gum, and psyllium (P < 0.01). Injection of radiolabeled lipoproteins indicated that pectin, guar gum, and psyllium intakes resulted in more rapid VLDL and LDL apo B turnover and lower LDL apo B flux in guinea pigs fed guar gum and psyllium. These results suggest that the secretion rate of apo B, compositional changes in lipoproteins occurring in the intravascular compartment, and up-regulation of LDL receptors-associated with faster LDL apo B turnover rates-are secondary metabolic responses induced by dietary fiber that contribute to the lowering of plasma cholesterol concentrations.

Animals↗

PubMed1996

Subungual hemorrhages. A primary manifestation of diabetes mellitus.

Subungual hemorrhages may be observed in a variety of systemic diseases and in some otherwise healthy persons. We describe three male patients who were referred because of toenail hemorrhages. Analytical investigations showed hyperglycemia in all the patients. Toenail bilateral hemorrhages were the first manifestation of previously undiagnosed type II diabetes mellitus in all cases. Ophthalmologic examination showed signs of background diabetic retinopathy in all three patients. The existence of retinopathy suggests that subungual hemorrhages might be due to microvascular involvement and could herald the presence of diabetes mellitus.

Aged↗

PubMed1996

Olive oil and rapeseed oil differ in their effect on plasma low-density lipoprotein metabolism in the guinea-pig.

The effects of olive oil and rapeseed oil, two different high-oleic-acid oils, on plasma LDL and hepatic cholesterol metabolism were compared in guinea-pigs. Animals were fed on semipurified diet containing 150 g fat/kg as either olive oil (OL), rapeseed oil plus 100 g palm oil/kg (C-P) or olive oil plus 350 g safflowerseed oil/kg (OL-S). Olive oil was enriched with safflowerseed oil (OL-S diet) to increase linoleic acid and to decrease palmitic acid concentrations, in order to evaluate whether differences in plasma LDL concentrations were due to intrinsic effects of the specific oil (rapeseed or olive oil) or to differences in the content of specific fatty acids. No differences due to dietary fat source were found in plasma total and HDL-cholesterol levels or in LDL composition. Plasma LDL-cholesterol levels were lower on the C-P diet than the OL diet (P < 0.05) while plasma LDL-cholesterol levels in animals fed on the OL-S diet were not significantly different from either dietary group (P > 0.05). The number of hepatic apo B/E (LDL) receptors was on average 25% higher in animals fed on the C-P diet compared with those fed on diets containing olive oil. Likewise, cardiac muscle lipoprotein lipase (EC 3.1.1.34) activity was significantly higher in the C-P group than in the OL and OL-S dietary groups. Dietary fat source had no effect on hepatic cholesterol levels or 3-hydroxy-3-methylglutaryl (HMG) CoA reductase (EC 1.1.1.34) activity. The results indicate that olive oil and rapeseed oil, both rich sources of monounsaturated fatty acids, differ in their effect on LDL metabolism in the guinea-pig.

Animals↗

PubMed1996

Dietary carbohydrate type and fat amount alter VLDL and LDL metabolism in guinea pigs.

The effects of low/high fat diets and simple/complex carbohydrate intake on specific aspects of plasma VLDL and LDL metabolism were evaluated. Guinea pigs were fed for 4 wk two different fat/carbohydrate concentrations: 2.5/58 (g/100 g) or 25/29 (g/100 g) with either sucrose or cornstarch as the sole carbohydrate source. Intake of high fat diets resulted in higher plasma cholesterol (P < 0.001), whereas sucrose intake resulted in higher plasma triacyglycerol (TAG) concentrations (P < 0.03). Intake of starch increased apolipoprotein (apo) B secretion rates (P < 0.001), and nascent VLDL were smaller and contained less TAG/apo B than particles from the sucrose-fed group (P < 0.01). Guinea pigs fed the starch diets had higher plasma VLDL apo B flux and faster VLDL apo B clearance than those fed sucrose diets (P < 0.01). In addition, more rapid VLDL removal from plasma in guinea pigs fed complex carbohydrate/high fat diets was associated with less conversion of VLDL to LDL and lower plasma cholesterol concentrations compared with the high fat/sucrose group (P < 0.01). Low fat compared with high fat intake resulted in 60% more rapid plasma LDL apo B fractional catabolic rates (FCR). The LDL apo B fractional catabolic rate of all dietary groups was inversely correlated with plasma cholesterol concentrations (r = -0.83, P < 0.001). These results demonstrate that in guinea pigs, low fat diets decrease plasma LDL cholesterol concentrations by increasing LDL turnover rates, and complex carbohydrates reduce plasma TAG by affecting the composition of nascent VLDL particles and by increasing VLDL apo B catabolism.

Animals↗

PubMed1996

Renal infarction in a severely hypertensive patient with lupus erythematosus and antiphospholipid antibodies.

Systemic lupus erythematosus (SLE) patients, specially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations. However, renal infarction has been rarely reported in these patients. The case of a young female with renal infarction, diagnosed by renal arteriography and scintigraphy, and arterial hypertension (AH) is described. In subsequent years she also suffered several cerebrovascular accidents with important neurological sequelae. No evidence of systemic disease was observed at this time. Fourteen years after the renal infarction a diagnosis of SLE was established. Despite therapy with prednisone, acetylsalicylic acid, azathioprine and antihypertensive drugs the progression of the neurological disease led to death. The sudden appearance of severe AH in a young woman with a renal infarction should alert the clinician about a possible underlying renal artery thrombosis in association with SLE and antiphospholipid antibodies.

Adult↗

PubMed1996

Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig.

Guinea pigs were fed 15% (w/W) fat, high in lauric and myristic acids, a diet known to produce hypercholesterolemia in these animals. The diet was given alone or in combination with four doses of atorvastatin equivalent to 1, 3, 10, and 20 mg/kg per day. Atorvastatin reduced plasma LDL cholesterol concentrations by 46, 50, 53, and 70%, respectively (P < 0.001). Plasma apoB concentrations were reduced by atorvastatin (P < 0.001) and compositional changes occurred in VLDL and LDL with reductions of the relative proportion of cholesteryl ester and increases in triacylglycerol. A reduction in hepatic cholesteryl ester (66%) was observed only with the highest atorvastatin dose (20 mg/kg per day) while microsomal cholesterol was reduced by 30% with 3-20 mg/kg per day. Hepatic ACAT activity was down-regulated and apoB/E receptor number was increased by atorvastatin. In contrast, HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase were not affected by the drug. VLDL apoB secretion rates were decreased by atorvastatin treatment 59 and 76% with 3 and 20 mg/kg per day, respectively. Nascent VLDL particles were larger after drug treatment, showing an increased number in triacylglycerol molecules. These results support the hypothesis that the plasma LDL lowering induced by atorvastatin is due to a decreased secretion of apoB in combination with an increase of hepatic apoB/E receptors.

Animals↗

PubMed1995

Differential effects of simple vs. complex carbohydrates on VLDL secretion rates and HDL metabolism in the guinea pig.

Guinea pigs were fed isocaloric diets containing 52% (w/w) carbohydrate, either sucrose or starch, to investigate effects of simple vs. complex carbohydrates on plasma VLDL and HDL metabolism. Plasma cholesterol concentrations were not different between dietary groups while plasma triacylglycerol (TAG) and VLDL cholesterol levels were significantly increased in animals fed the sucrose diet (P < 0.05). Hepatic VLDL TAG secretion rates measured following intravenous injection of Triton WR-1339 were not affected by carbohydrate type whereas the rate of apo B secretion was 1.9-fold higher in sucrose fed animals (P < 0.02). Nascent VLDL from the sucrose group contained less TAG per apo B suggesting that the higher plasma TAG in animals fed simple carbohydrates results from increased secretion of VLDL particles with lower TAG content. Sucrose fed animals exhibited higher concentrations of hepatic free cholesterol (P < 0.01) while hepatic TAG levels and acyl CoA:cholesterol acyltransferase (ACAT) activity were not different between groups. Plasma HDL cholesterol concentrations and composition, and plasma lecithin cholesterol acyltransferase (LCAT) activity were not affected by diet yet there was a positive correlation between HDL cholesteryl ester content and LCAT activities (r = 0.70, P < 0.05). Hepatic membranes from the sucrose group had a higher hepatic HDL binding protein number (Bmax) with no changes in the dissociation constant (Kd). These results suggest that at the same carbohydrate energy intake, simple sugars induce modest changes in HDL metabolism while VLDL metabolism is affected at multiple sites, as indicated by the higher concentrations of hepatic cholesterol, dissociation in the synthesis rates of VLDL components, and compositional changes in nascent and mature VLDL.

Animals↗

PubMed1995

High density lipoprotein metabolism is altered by dietary cholesterol but not fat saturation in guinea pigs.

To study dietary fat and cholesterol effects on plasma high density lipoprotein (HDL) metabolism and rates of apolipoprotein (apo) A-I catabolism, guinea pigs were fed 15% (wt/wt) lard- or corn oil-based diets with 0.01% (basal), 0.08%, 0.17% or 0.33% cholesterol. Absorbed dietary cholesterol provided 6%, 50%, 100% and 200%, respectively, of the daily endogenous cholesterol synthetic mass. While total plasma cholesterol concentrations increased significantly above basal levels at the 0.17% and 0.33% cholesterol intakes, plasma apo E-free HDL (EoHDL) cholesterol concentrations did not increase significantly until the 0.33% cholesterol level (P < 0.001). Fractional catabolic rates (FCR) of injected [131I]-apo A-I were not altered by dietary treatment, either fat saturation or cholesterol, but were inversely correlated with plasma EoHDL cholesterol levels (r = -0.622), suggestive of a regulatory role of turnover rates on HDL cholesterol levels independent of dietary treatment. Analysis of the high affinity EoHDL binding to isolated hepatic membranes suggested that hepatic binding was not a determinant of HDL catabolism, as dietary cholesterol-induced decreases in Bmax (binding capacity) were not correlated with changes in apo A-I FCR. Even though dietary cholesterol was associated with increased plasma EoHDL cholesterol and with decreased HDL binding protein Bmax, these values did not correlate with each other nor with effects on apo A-I FCR.

Animals↗

PubMed1995

Carbohydrate type and amount alter intravascular processing and catabolism of plasma lipoproteins in guinea pigs.

To test the effects of exchanging dietary complex and simple carbohydrate for fat calories on lipoprotein metabolism, guinea pigs were fed two different fat/carbohydrate ratios: 2.5:58% (w/w) or 25:29% (w/w) with either sucrose or starch as the carbohydrate source. Animals fed high-fat had higher plasma low-density lipoprotein (LDL) and hepatic cholesterol concentrations than animals fed low-fat diets (P < 0.01). The cholesteryl ester content per particle was higher, and the number of triacylglycerol (TAG) molecules was lower in very low density lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high-fat/sucrose resulted in higher plasma LDL concentrations than intake of high-fat/starch, and animals fed low-fat/starch had the highest plasma TAG concentrations associated with VLDL particles containing more TAG molecules, as well as a TAG-enriched LDL. The activity of plasma lecithin cholesteryl:acyl transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart lipoprotein lipase (LPL) activity was higher in animals fed high-fat diets. Hepatic apoprotein B/E (apo B/E) receptor number (Bmax) was increased 21% with low-fat diets (P < 0.01). These results suggest that the hypercholesterolemia induced by high-fat and by sucrose intake are associated with a higher plasma LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the action of LPL, might be more readily converted to LDL through the delipidation cascade leading to downregulation of hepatic apo B/E receptors. The hypertriglyceridemia associated with low-fat intake may result from increased production of VLDL TAG, which would explain the increased TAG content and the higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet.

Animals↗

PubMed1995

Carbohydrate-fat exchange and regulation of hepatic cholesterol and plasma lipoprotein metabolism in the guinea pig.

Adult female guinea pigs were fed semipurified diets containing increasing concentrations of saturated fat (2.5%, 7.5%, 15%, and 25% wt/wt) to determine effects of exchanging fat-carbohydrate calories on lipoprotein metabolism. Plasma very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) did not vary but plasma low-density lipoprotein (LDL) concentrations increased with increasing fat calories. LDL cholesterol values were 42 +/- 25, 61 +/- 17, 92 +/- 25, and 98 +/- 21 mg/dL (mean +/- SD, n = 5), respectively. The relative proportion of cholesteryl ester increased and triacylglycerol (TAG) decreased for VLDL, LDL, and HDL as dietary fat increased. Plasma lecithin cholesterol acyltransferase (LCAT) activity was positively correlated with HDL cholesteryl ester content. Hepatic cholesterol and TAG concentrations were highest in animals fed 25% fat (P < .01). Hepatic apolipoprotein (apo) B/E receptor maximal binding capacity (Bmax) was 30% higher in animals fed 2.5% and 7.5% fat as compared with those fed 15% and 25% fat (P < .01) and inversely correlated with plasma LDL (r = -.85, P < .01). In contrast, HDL binding to guinea pig hepatic membranes exhibited a significant positive correlation with dietary fat quantity (r = .98, P < .001), consistent with a dose-response with increasing fat calories. The activity of hepatic 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase was not affected by the amount of dietary fat, whereas the activity of acyl CoA:cholesterol acyltransferase (ACAT) was significantly increased in animals fed 25% fat (P < .05). Hepatic free-cholesterol and ACAT activity exhibited a positive correlation for all dietary groups (r = .75, P < .001). These results demonstrate that exchange of saturated dietary fat for carbohydrate calories results in significant modifications in the regulation of metabolic pathways that determine plasma LDL concentrations and hepatic cholesterol homeostasis.

Animals↗

PubMed1995

Guar gum effects on plasma low-density lipoprotein and hepatic cholesterol metabolism in guinea pigs fed low- and high-cholesterol diets: a dose-response study.

Guinea pigs were fed semipurified diets containing either 0% or 12.5% guar gum (GG) with 0.04% cholesterol or increasing concentrations of GG (0%, 2.5%, 5%, 7.5%, 10%, and 12.5%) with 0.25% cholesterol (by wt). Compared to the 0% GG diet with 0.04% cholesterol, intake of the 12.5% GG diet with 0.04% cholesterol lowered plasma low-density-lipoprotein (LDL) concentrations, the ratio of LDL cholesteryl ester to protein, hepatic cholesterol concentrations, and the activity of acyl-CoA:cholesterol acyltransferase (ACAT), and increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and hepatic apo B/E receptor number (P < 0.01). Intake of GG by animals fed 0.25% cholesterol diets resulted in modest effects on hepatic cholesterol pools and plasma LDL concentrations; however, significant negative correlations were found between both plasma LDL cholesterol and hepatic free cholesterol concentrations with the amount of dietary GG (P < 0.05). Hepatic HMG-CoA reductase was suppressed by the 0.25% cholesterol intake, and GG did not reverse this suppression. In contrast, ACAT activity was negatively correlated with the amount of dietary GG (P < 0.05), and GG intake increased the number of hepatic apo B/E receptors at all intakes with the 0.25% cholesterol diets. These results demonstrate that intake of GG significantly alters endogenous cholesterol metabolism by decreasing hepatic cholesterol pools, altering hepatic cholesterol homeostasis, and reducing plasma LDL concentrations.

Animals↗

PubMed1995

Psyllium reduces plasma LDL in guinea pigs by altering hepatic cholesterol homeostasis.

Male Hartley guinea pigs were fed semipurified diets containing various levels of psyllium and cholesterol to determine mechanisms by which psyllium lowers plasma low density lipoprotein (LDL) concentrations. Four diets were tested: control diets with 12.5% (w/w) cellulose, and psyllium diets in which cellulose was partially replaced with 7.5% (w/w) psyllium. Two levels of dietary cholesterol were used, either low (LC, 0.04%, w/w) or high (HC, 0.25%, w/w). Plasma LDL was reduced by 30 and 54% with psyllium intake in the LC and HC groups, respectively (P < 0.001), while plasma very low density lipoprotein (VLDL) was lowered only in the HC group (P < 0.001). Psyllium intake modified LDL composition and size compared to LDL from control animals with a lower proportion of cholesteryl ester and higher proportion of triacylglycerol, lower molecular weight, smaller diameter, and higher peak density (P < 0.001). Plasma VLDL from animals fed the psyllium-HC diet compared to the control-HC contained lower relative proportions of free and esterified cholesterol and a higher proportion of triacylglycerol, compositional characteristics similar to VLDL from animals fed LC diets. Hepatic free and esterified cholesterol concentrations were significantly reduced by psyllium an average of 25 and 55%, respectively, while hepatic HMG-CoA reductase activity was increased in both psyllium groups compared to the respective controls (P < 0.001). In addition, psyllium intake reduced hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity in both the LC and HC groups (P < 0.001) and increased hepatic membrane apoB/E receptor number (Bmax) by 17 and 52% for animals fed LC and HC diets, respectively (P < 0.005). Significant psyllium-induced increases in cholesterol 7 alpha-hydroxylase of 4- and 1.6-fold were also observed in animals fed the LC and HC diets respectively (P < 0.001). These results indicate that psyllium generates a negative cholesterol balance across the liver which results in induction of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase and suppression of ACAT activities, upregulation of apoB/E receptors, and secretion of smaller VLDL particles, metabolic alterations that contribute to a lowering of plasma LDL cholesterol levels.

Animals↗

PubMed1995

Regulation of guinea pig very low density lipoprotein secretion rates by dietary fat saturation.

We investigated the effects of dietary fat saturation on very low density lipoprotein (VLDL) production in guinea pigs fed semipurified diets containing 15% (w/w) fat, either corn oil (CO, 58% linoleic acid), lard (LA, 42% oleic and 24% palmitic acids) or palm kernel oil (PK, 52% lauric and 18% myristic acids) for 4 weeks. Animals were given an intravenous injection of Triton WR 1339 to block VLDL catabolism and rates of VLDL triacylglycerol (TAG) and apolipoprotein (apo) B secretion were measured over time. Plasma TAG concentrations increased linearly for 8 h (r = 0.99) and VLDL-TAG secretion rates were significantly higher (P < 0.01) in guinea pigs fed LA (72.7 +/- 14.7 mg/kg-h, n = 12) compared to animals fed PK (55.4 +/- 13.4 mg/kg-h, n = 12) or CO (48.6 +/- 17.5 mg/kg-h, n = 15). VLDL apoB secretion rates were highest in PK-fed animals (3.1 +/- 1.8 mg/kg-h) compared to guinea pigs fed LA (1.5 +/- 0.8 mg/kg-h) or CO (1.1 +/- 0.6 mg/kg-h) diets (P < 0.005). Concurrent with analysis of VLDL secretion, turnover of 125I-labeled LDL was measured. Low density lipoprotein (LDL) fractional catabolic rates were not altered by Triton treatment and LDL apoB specific radioactivity (cpm/microgram) did not change over time indicating that: a) the Triton blockage of VLDL catabolism was complete, and b) there was no direct secretion of LDL by the liver. These data demonstrate that intake of lard increases the rate of VLDL-triacylglycerol secretion and that nascent VLDL particles from the lard and corn oil diet groups have the same relative triacylglycerol content, whereas palm kernel oil intake increases secretion of VLDL particles which have a reduced triacylglycerol content. These results demonstrate that dietary fat chain length and saturation have specific effects on VLDL secretion rates affecting both particle number and composition.

Animals↗

PubMed1995

Gender differences in response to dietary soluble fiber in guinea pigs: effects of pectin, guar gum, and psyllium.

Dietary soluble fiber significantly lowers plasma low density lipoprotein (LDL) cholesterol concentrations in humans and animals. In male guinea pigs, alterations in hepatic cholesterol homeostasis induced by dietary fiber in part account for the decrease in plasma LDL levels (Fernandez et al. 1994. Am. J. Clin. Nutr. 59: 869-878; 1995. 61: 127-134, and J. Lipid Res. 1995. 36: 1128-1138). To test whether dietary fiber elicited similar hypocholesterolemic responses in both genders, female guinea pigs were fed diets containing 12.5% pectin (PE), 12.5% guar gum (GG), 7.5% psyllium (PSY), or 12.5% cellulose (control diet). In addition, physiological (0.04%) (LC) or pharmacological (0.25%) (HC) amounts of cholesterol were tested with the fibers to determine whether dietary cholesterol altered the plasma cholesterol response. Significant reductions in plasma cholesterol were observed in females fed LC diets with PE, GG, or PSY (P < 0.01) while the responses to fiber with high cholesterol intake were more moderate. Hepatic cholesterol concentrations were reduced in the LC group (P < 0.001) with increased HMG-CoA reductase and cholesterol 7 alpha-hydroxylase and decreased acyl CoA:cholesterol acyltransferase (ACAT) activities accompanied by a reduction in hepatic cholesterol pools induced by fiber intake. In addition, plasma LDL lowering in animals fed the LC diets was associated with increases in hepatic LDL receptor Bmax values. Effects of fiber on hepatic cholesterol in animals fed HC diets were moderate and hepatic enzymes were not altered to the same extent as in the LC groups. For the LC groups there was no gender effect on the magnitude of plasma LDL lowering, depletion of hepatic cholesterol, or alterations in hepatic cholesterol metabolism, although hepatic HMG-CoA reductase and ACAT activities were lower in females compared to males (P < 0.01). In contrast, females fed the control HC diet had higher plasma LDL levels than males and dietary fiber did not reduce hepatic cholesterol concentrations nor alter hepatic enzyme activities as effectively as in males. These studies demonstrate that female, compared to male, guinea pigs are more responsive to a dietary cholesterol challenge and, that with this pharmacological perturbation, fiber effects are moderate compared to males. In contrast, with low cholesterol intakes, the cholesterol lowering effects of fiber are similar in both genders.

Animals↗

PubMed1995

Distinct mechanisms of plasma LDL lowering by dietary fiber in the guinea pig: specific effects of pectin, guar gum, and psyllium.

Pectin (PE), guar gum (GG), and psyllium (PSY) lower plasma low density lipoprotein (LDL) cholesterol concentrations in guinea pigs with different orders of magnitude by inducing defined alterations in hepatic cholesterol homeostasis (Fernandez et al. 1994. Am. J. Clin. Nutr. 59: 869-879; 61: 127-134 and 1995. J. Lipid Res. 36: 1128-1138). To further explore specific mechanisms responsible for the differences in plasma and hepatic cholesterol lowering, the effects of these fibers were evaluated on cholesterol absorption, hepatic cholesterol 7 alpha-hydroxylase activity, the rate-limiting enzyme of bile acid synthesis, and in vivo LDL transport to target specific primary and secondary mechanisms accounting for the observed responses. Fibers were fed with physiological (0.04%), low cholesterol (LC), or pharmacological high cholesterol (HC) (0.25%) levels to assess whether cholesterol intake influences plasma LDL lowering mechanisms. Intake of PE, GG, or PSY with LC or HC diets lowered plasma and hepatic cholesterol concentrations (P < 0.001). PE and PSY up-regulated 7 alpha-hydroxylase activity 3-fold with LC and PE by 5-fold with HC diets. In contrast, GG intake had no effect on 7 alpha-hydroxylase activity. Cholesterol absorption was reduced 30% by PE intake while no differences were found between control and PSY groups. GG reduced cholesterol absorption only with HC diets. Intake of PE, GG, or PSY with HC diets resulted in faster plasma LDL fractional catabolic rates (FCR) (P < 0.01) with no effect on LDL apoB flux rates (FR) or pool size, suggesting that fiber reduced LDL cholesterol concentration without decreasing the number of LDL particles. In addition to reducing LDL apoB FR, PE and PSY increased LDL FCR with HC diets while GG effects were limited to lowering LDL apoB FR. These results indicate that the distinctive reductions in hepatic cholesterol induced by PE, GG, and PSY associated with plasma cholesterol lowering result from different mechanisms specific to each fiber and that the levels of dietary cholesterol contribute to the different metabolic responses.

Analysis of Variance↗

PubMed1994

Citrus pectin and cholesterol interact to regulate hepatic cholesterol homeostasis and lipoprotein metabolism: a dose-response study in guinea pigs.

Guinea pigs were fed increasing concentrations of citrus pectin (CP) (0-12.5%, wt/wt) with low (LC, 0.04%) or high (HC, 0.25%) cholesterol. Animals fed LC diets had reduced plasma LDL concentrations with 10% and 12.5% CP and hepatic membrane apolipoprotein B/E receptor expression increased with high dosages of CP. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased with 12.5% CP whereas hepatic cholesterol concentrations and acyl-CoA:cholesterol acyltransferase (ACAT) activity were not different. In contrast, with HC diets, plasma LDL concentrations were reduced in a dose-response manner by 29%, 30%, and 67% with 7.5%, 10%, and 12.5% CP intake (P < 0.001) and apolipoprotein B/E receptor number was increased and inversely correlated with plasma LDL in the HC group (r = -0.81, P < 0.005). Animals fed HC diets had a dose-dependent decrease in hepatic cholesterol and ACAT activity, with intake of 12.5% CP having the major effect. Hepatic HMG-CoA reductase activity was suppressed by HC diets and only intake of 12.5% CP reversed this suppression. The most significant effects of CP on hepatic cholesterol, enzymes of hepatic cholesterol homeostasis, and the apolipoprotein B/E receptor were in animals fed the HC diets. These metabolic alterations partially explain the reduced plasma LDL of guinea pigs fed large amounts of CP.

Animals↗