Marcela Vergara-Jimenez

JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

BackgroundMicrosomal transfer protein inhibitors (MTPi) have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG). However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver.MethodsMale guinea pigs (n = 10 per group) were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control), 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism.ResultsPlasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P < 0.05). Atorvastatin had the most pronounced hypolipidemic effects with a 35% reduction in LDL cholesterol and 40% reduction in TG. JTT-130 did not induce hepatic lipid accumulation compared to controls. Cholesteryl ester transfer protein (CETP) activity was reduced in a dose dependent manner by increasing doses of MTPi and guinea pigs treated with atorvastatin had the lowest CETP activity (P < 0.01). In addition the number of molecules of cholesteryl ester in LDL and LDL diameter were lower in guinea pigs treated with atorvastatin. In contrast, hepatic enzymes involved in maintaining cholesterol homeostasis were not affected by drug treatment.ConclusionThese results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

Pectin and psyllium decrease the susceptibility of LDL to oxidation in guinea pigs

These studies were undertaken to determine whether pectin (PE) and psyllium (PSY) intake affect the circulating levels of alpha-tocopherol and the susceptibility of low density lipoprotein (LDL) to oxidation. For that purpose, male Hartley guinea pigs were fed 19 g/100 g of a fat mix with a 2:1:1 ratio of saturated:polyunsaturated:monounsaturated fatty acids and 35 g/100 g total carbohydrate with 80% of the carbohydrate energy contributed by sucrose. Diets were identical in composition except for the fiber source: cellulose (control diet), PE, or PSY. Guinea pigs fed PE or PSY had 36% and 67% lower plasma cholesterol concentrations, respectively, compared with controls (P < 0.001). This plasma cholesterol lowering was associated with both very low density lipoproteins and LDL cholesterol fractions. Intake of PE or PSY resulted in 54% lower plasma triacylglycerol (TAG) concentrations compared with the control group (P < 0.001). LDL from PE and PSY fed guinea pigs contained fewer molecules of cholesteryl ester, and alpha-tocopherol concentrations in this particle were 49% and 66% higher, respectively, compared with controls. In addition, LDL from guinea pigs fed soluble fiber exhibited less susceptibility to oxidation than those from the control group, as determined by thiobarbituric acid-reactive substances formation. Hepatic free and esterified cholesterol were 32% lower and hepatic TAG was 25% lower in guinea pigs fed PE and PSY compared with controls. The data from these studies confirm that PE and PSY reverse the hyperlipidemia associated with high fat-sucrose diets and demonstrate a potential antioxidant effect of soluble fiber on circulating LDL.

RESISTANT STARCH AND CHOLESTYRAMINE HAVE DISTINCT EFFECTS ON HEPATIC CHOLESTEROL METABOLISM IN GUINEA PIGS FED A HYPERCHOLESTEROLEMIC DIET

Abstract The effects of resistant starch (RS) and cholestyramine (CHY) on cholesterol metabolism were tested in guinea pigs. Animals were fed cellulose (14 g100 g) (control diet) RS (10 g100g) or CHY (1 g100 g) for a period of 4 weeks. All diets contained 19 g100 g fat, 0.17 g100 g cholesterol and 36 g100 g carbohydrate with sucrose contributing 80% to the carbohydrate energy. Guinea pigs fed RS and those treated with CHY had 27% and 75% lower plasma cholesterol concentrations than the control group (P

Lime-treated corn husks lower plasma LDL cholesterol in guinea pigs by altering hepatic cholesterol metabolism

Lime-treated corn husks (LTCH) containing 69% of fiber (5.0% as soluble fiber) were evaluated on their hypolipidemic properties in guinea pigs. Animals were fed two doses of corn husks replacing dietary fiber: 7,5% and 10% (w/w) and LTCH effects on hepatic cholesterol metabolism and lipoprotein levels were compared to a control diet containing cellulose. LTCH significantly lowered plasma LDL cholesterol by 25% (P < 0.01) and VLDL cholesterol by 37% (P < 0.05), although a dose effect was not observed in this parameter. Plasma triacylglycerol (TAG) concentrations and HDL cholesterol levels were not affected by LTCH intake. The number of cholesteryl ester, TAG and phospholipid molecules were lower in VLDL from animals fed LTCH diets compared to control (P < 0.01) indicating modifications on VLDL size that were confirmed by the smaller calculated VLDL diameter of guinea pigs treated with LTCH. In addition, LTCH intake resulted in a smaller, cholesteryl ester depleted LDL particle compared with LDL derived from control animals. Hepatic cholesterol and TAG were not affected by LTCH, however, microsomal-free cholesterol was lower in animals fed LTCH compared with control. In agreement with the observed reductions on microsomal cholesterol, HMG-CoA reductase activity was upregulated 87% and 100%, ACAT downregulated 54% and 65% and cholesterol 7α-hydroxylase activity upregulated 120% and 180% by LTCH diets in a dose dependent manner (P < 0.01). In addition, LDL binding to hepatic membranes (Bmax) was higher in animals fed LTCH diets. These results indicate that the lower plasma VLDL and LDL cholesterol concentrations induced by LTCH intake are associated with decreases in microsomal cholesterol that alter the regulatory enzymes of cholesterol homeostasis and upregulate LDL receptors.

Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease

Moringa Oleifera (MO), a plant from the family Moringacea is a major crop in Asia and Africa. MO has been studied for its health properties, attributed to the numerous bioactive components, including vitamins, phenolic acids, flavonoids, isothiocyanates, tannins and saponins, which are present in significant amounts in various components of the plant. Moringa Oleifera leaves are the most widely studied and they have shown to be beneficial in several chronic conditions, including hypercholesterolemia, high blood pressure, diabetes, insulin resistance, non-alcoholic liver disease, cancer and overall inflammation. In this review, we present information on the beneficial results that have been reported on the prevention and alleviation of these chronic conditions in various animal models and in cell studies. The existing limited information on human studies and Moringa Oleifera leaves is also presented. Overall, it has been well documented that Moringa Oleifera leaves are a good strategic for various conditions associated with heart disease, diabetes, cancer and fatty liver.

Prevalence of Self-Reported Gluten Sensitivity and Adherence to a Gluten-Free Diet in Argentinian Adult Population

Background: Previous studies suggest that the prevalence of wheat/gluten sensitivity and adherence to a gluten-free diet (GFD) are high in Latin population despite a poor diagnosis of celiac disease. However, these prevalence rates still remain unknown in most Latin American countries. Methods: A cross-sectional survey study was conducted in Santa Fe, Argentina. Results: The estimated self-reported prevalence rates were (95% Confidence Interval [CI]): self-reported gluten sensitivity (SR-GS) 7.61% (6.2–9.2), SR-GS currently following a GFD 1.82% (1.2–2.7), celiac disease 0.58% (0.3–1.2), wheat allergy 0.33% (0.12–0.84), self-reported non-celiac gluten sensitivity (SR-NCGS) 6.28% (5.1–7.8), SR-NCGS currently following a GFD 0.91% (0.5–1.6), and adherence to a GFD 6.37% (5.1–7.9). SR-GS was more common in women (6.0%; p < 0.001) and associated with irritable bowel syndrome (p < 0.001). Among the GFD followers, 71.4% were doing it for reasons other than health-related benefits and 50.6% without medical/dietitian advice. In the non-SR-GS group, the main motivations for following a GFD were weight control and the perception that a GFD is healthier. Conclusion: In Argentina, gluten sensitivity is commonly reported and it seems that physicians/gastroenterologists are aware of celiac disease diagnosis. Trustable information about the benefits and potential consequences of following a GFD should be given to the general population.

Compared to an Oatmeal Breakfast, Two Eggs/Day Increased Plasma Carotenoids and Choline without Increasing Trimethyl Amine N-Oxide Concentrations

ABSTRACT Background: Habitual consumption of eggs has been hypothesized to positively modify biomarkers of cardiovascular disease risk through proposed antioxidant properties. Objectives: To examine this relationship, 50 young, healthy men and women were enrolled into a randomized crossover clinical intervention. Methods: Participants consumed either 2 eggs per day or one packet of oatmeal a day for 4 weeks, followed by a 3-week wash-out and crossed over to the alternate breakfast. Fasting blood samples and peripheral blood mononuclear cells (PBMCs) were collected at the end of each intervention period. Results: Increases in plasma large high-density lipoprotein (HDL) and large low-density lipoprotein (LDL) particle concentrations as measured by nuclear magnetic resonance were found following egg consumption (p < 0.001, p < 0.05), respectively, with increases in apolipoprotein concentration as well (p < 0.05). Though there was no difference in the intake of antioxidants lutein and zeaxanthin, a significant increase in plasma concentrations of these carotenoids was observed (p < 0.001) after egg consumption. There was no change in lecithin–cholesterol acyl transferase, cholesteryl ester transfer protein, or paroxanase-1 arylesterase activities between breakfast interventions. Dietary and plasma choline were both higher following egg consumption compared to oatmeal consumption (p < 0.001); however, there was no change in plasma trimethylamine N-oxide (TMAO) concentrations. Two eggs per day had no impact on PBMC gene expression related to cholesterol metabolism, oxidation, or TMAO production. Conclusions: These results suggest that compared to oatmeal, consumption of 2 eggs for breakfast provided increased plasma carotenoids and improved biomarkers of cardiovascular disease (CVD) risk while not affecting TMAO levels in this population.

Consuming Two Eggs per Day, as Compared to an Oatmeal Breakfast, Decreases Plasma Ghrelin while Maintaining the LDL/HDL Ratio

Eggs contain high quality protein, vitamins, minerals and antioxidants, yet regular consumption is still met with uncertainty. Therefore, the purpose of this study was to compare the effects of consuming two eggs per day or a heart-healthy oatmeal breakfast on biomarkers of cardiovascular disease (CVD) risk and satiety measures in a young, healthy population. Fifty subjects participated in a randomized crossover clinical intervention; subjects were randomly allocated to consume either two eggs or one packet of oatmeal per day for breakfast for four weeks. After a three-week washout period, participants were allocated to the alternative breakfast. Fasting blood samples were collected at the end of each intervention period to assess plasma lipids and plasma ghrelin. Subjects completed visual analog scales (VAS) concurrent to dietary records to assess satiety and hunger. Along with an increase in cholesterol intake, there were significant increases in both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol following the egg consumption period (p < 0.01). However, there was no difference in the LDL/HDL ratio, a recognized biomarker of CVD risk, nor in the plasma glucose, triglycerides or liver enzymes, between diet periods. Several self-reported satiety measures were increased following the consumption of eggs, which were associated with lower plasma ghrelin concentrations (p < 0.05). These results demonstrate that compared to an oatmeal breakfast, two eggs per day do not adversely affect the biomarkers associated with CVD risk, but increase satiety throughout the day in a young healthy population.

Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism

To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group (p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1β and interferon-γ, were lowest in the HM group (p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls (p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver.

Differences in response between 18 carbon fatty acids and 12 14 carbon saturated fatty acids on plasma cholesterol in Guinea pigs

Abstract Male guinea pigs were fed four different diets rich in lauric plus myristic (LM), stearic (ST), oleic (OL) or linoleic (LN) fatty acids to compare the effects of 18 carbon fatty acids with different degrees of saturation with 12 14 carbon saturated fatty acids on hepatic cholesterol metabolism. Animals fed the LM diet had 76–100% higher plasma total cholesterol and apo B concentrations than those fed ST, OL or LN diets (P B E receptor number was highest in animals fed LN diet and intake of ST and OL diets resulted in higher hepatic apo B E receptor number compared to animals fed LM diets (P