Reduced Plasma Cholesterol Concentrations Research Articles

(Pro)renin Receptor Inhibition Reduces Plasma Cholesterol and Triglycerides but Does Not Attenuate Atherosclerosis in Atherosclerotic Mice.

Objective: Elevated plasma cholesterol concentrations contributes to ischemic cardiovascular diseases. Recently, we showed that inhibiting hepatic (pro)renin receptor [(P)RR] attenuated diet-induced hypercholesterolemia and hypertriglyceridemia in low-density lipoprotein receptor (LDLR) deficient mice. The purpose of this study was to determine whether inhibiting hepatic (P)RR could attenuate atherosclerosis.Approach and Results: Eight-week-old male LDLR−/− mice were injected with either saline or N-acetylgalactosamine-modified antisense oligonucleotides (G-ASOs) primarily targeting hepatic (P)RR and were fed a western-type diet (WTD) for 16 weeks. (P)RR G-ASOs markedly reduced plasma cholesterol concentrations from 2,211 ± 146 to 1,128 ± 121 mg/dL. Fast protein liquid chromatography (FPLC) analyses revealed that cholesterol in very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL)/LDL fraction were potently reduced by (P)RR G-ASOs. Moreover, (P)RR G-ASOs reduced plasma triglyceride concentrations by more than 80%. Strikingly, despite marked reduction in plasma lipid concentrations, atherosclerosis was not reduced but rather increased in these mice. Further testing in ApoE−/− mice confirmed that (P)RR G-ASOs reduced plasma lipid concentrations but not atherosclerosis. Transcriptomic analysis of the aortas revealed that (P)RR G-ASOs induced the expression of the genes involved in immune responses and inflammation. Further investigation revealed that (P)RR G-ASOs also inhibited (P)RR in macrophages and in enhanced inflammatory responses to exogenous stimuli. Moreover, deleting the (P)RR in macrophages resulted in accelerated atherosclerosis in WTD fed ApoE−/− mice.Conclusion: (P)RR G-ASOs reduced the plasma lipids in atherosclerotic mice due to hepatic (P)RR deficiency. However, augmented pro-inflammatory responses in macrophages due to (P)RR downregulation counteracted the beneficial effects of lowered plasma lipid concentrations on atherosclerosis. Our study demonstrated that hepatic (P)RR and macrophage (P)RR played a counteracting role in atherosclerosis.

Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence.

Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.

Productive performance, lipid profile and caecum microbial counts of growing rabbits treated with humic acid.

The aim of the present study was to evaluate the effect of a humic acid (HA)-supplemented diet on productive performance and some physiological parameters of growing rabbits. A total of 80 weaned V-line rabbits at an age of 4weeks were randomly divided into four groups. Rabbits of groups 2, 3 and 4 were fed diet containing 35 (HA35), 70 (HA70) and 105 (HA105) mg Humic acid/kg diet while the first group served as control (HA0). Body weight gain was positively affected by HA treatment. HA105 rabbits had the improved feed conversion value. HA treatments had significantly reduced plasma cholesterol concentration and significant increased red blood cells, white blood cells count and plasma high-density lipoprotein concentrations. However, serum aspartate amino transferase and alanine amino transferase activities, creatinine and the apparent nutrients digestibility values were not affected by HA treatments. Organic matter digestibility of all HA-treated groups significantly increased compared with HA0. At 63days of age (after 35days of treatment), caecum microbial counts decreased (total bacteria and Escherichia coli) with HA treatments. Generally HA could be considered as a biological as growth promoter feed additive alternative to antibiotics.

Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants

Dietary plant sterols, such as campesterol and sitosterol, reduce plasma cholesterol concentrations, but any relationship to plaque development and CVD remains unclear. Some epidemiologic studies have suggested that elevated plasma plant sterol concentrations are atherogenic, including the Framingham Offspring Study that identified a positive association between plant sterol concentrations and CVD status. We hypothesized that this suggested atherogenicity relates to the oxidation status of plant sterols (i.e., concentrations of plasma oxyphytosterols). Therefore, in the Framingham Offspring Study cohort, we measured plasma oxyphytosterol concentrations in 144 patients with documented CVD and/or more than 50% carotid stenosis and 383 matched controls. We analyzed plasma oxyphytosterol concentrations by GC/MS/MS and performed conditional logistic regression analysis to determine associations between plasma plant sterol or oxyphytosterol concentrations and CVD status. We found that higher total cholesterol (TC)-standardized campesterol concentrations [odds ratio (OR): 2.36; 95% CI: 1.60, 3.50] and higher sitosterol concentrations (OR: 1.47; 95% CI: 1.09, 1.97) were significantly associated with increased CVD risk, as in the earlier study. However, the sum of absolute oxyphytosterol concentrations (OR: 0.99; 95% CI: 0.81, 1.21) and the sum of TC-standardized oxyphytosterol concentrations (OR: 0.98; 95% CI: 0.80, 1.19) were not associated with an increased CVD risk. Results were comparable for individual absolute and TC-standardized oxycampesterol and oxysitosterol concentrations. Plasma nonoxidized TC-standardized sitosterol and campesterol concentrations showed weak or no correlations with oxyphytosterol concentrations, while all individual plasma concentrations of oxyphytosterol correlated with each other. In conclusion, circulating plasma oxyphytosterols are not associated with CVD risk in the Framingham Offspring Study.

Obeticholic acid ameliorates dyslipidemia but not glucose tolerance in mouse model of gestational diabetes.

Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor farnesoid X receptor (FXR) has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA), improves insulin sensitivity in patients with type 2 diabetes with nonalcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57BL/6J mice were fed a high-fat diet (HFD; 60% kcal from fat) for 4 wk before and throughout pregnancy to induce GDM. The impact of the diet supplemented with 0.03% OCA throughout pregnancy was studied. Pregnant HFD-fed mice displayed insulin resistance and dyslipidemia. OCA significantly reduced plasma cholesterol concentrations in nonpregnant and pregnant HFD-fed mice (by 22.4%, P < 0.05 and 36.4%, P < 0.001, respectively) and reduced the impact of pregnancy on insulin resistance but did not change glucose tolerance. In nonpregnant HFD-fed mice, OCA ameliorated weight gain, reduced mRNA expression of inflammatory markers in white adipose tissue, and reduced plasma glucagon-like peptide 1 concentrations (by 62.7%, P < 0.01). However, these effects were not evident in pregnant mice. OCA administration can normalize plasma cholesterol levels in a mouse model of GDM. However, the absence of several of the effects of OCA in pregnant mice indicates that the agonistic action of OCA is not sufficient to overcome many metabolic consequences of the pregnancy-associated reduction in FXR activity.

Plasma oxyphytosterol concentrations are not associated with CVD status in framingham offspring study participants

Dietary plant sterols, such as campesterol and sitosterol, reduce plasma cholesterol concentrations, but any relationship to plaque development and CVD remains unclear. Some epidemiologic studies have suggested that elevated plasma plant sterol concentrations are atherogenic, including the Framingham Offspring Study that identified a positive association between plant sterol concentrations and CVD status. We hypothesized that this suggested atherogenicity relates to the oxidation status of plant sterols (i.e., concentrations of plasma oxyphytosterols). Therefore, in the Framingham Offspring Study cohort, we measured plasma oxyphytosterol concentrations in 144 patients with documented CVD and/or more than 50% carotid stenosis and 383 matched controls. We analyzed plasma oxyphytosterol concentrations by GC/MS/MS and performed conditional logistic regression analysis to determine associations between plasma plant sterol or oxyphytosterol concentrations and CVD status. We found that higher total cholesterol (TC)-standardized campesterol concentrations [odds ratio (OR): 2.36; 95% CI: 1.60, 3.50] and higher sitosterol concentrations (OR: 1.47; 95% CI: 1.09, 1.97) were significantly associated with increased CVD risk, as in the earlier study. However, the sum of absolute oxyphytosterol concentrations (OR: 0.99; 95% CI: 0.81, 1.21) and the sum of TC-standardized oxyphytosterol concentrations (OR: 0.98; 95% CI: 0.80, 1.19) were not associated with an increased CVD risk. Results were comparable for individual absolute and TC-standardized oxycampesterol and oxysitosterol concentrations. Plasma nonoxidized TC-standardized sitosterol and campesterol concentrations showed weak or no correlations with oxyphytosterol concentrations, while all individual plasma concentrations of oxyphytosterol correlated with each other. In conclusion, circulating plasma oxyphytosterols are not associated with CVD risk in the Framingham Offspring Study.

Roux-en-Y gastric bypass reduces plasma cholesterol in diet-induced obese mice by affecting trans-intestinal cholesterol excretion and intestinal cholesterol absorption.

Bariatric surgery appears as the most efficient therapeutic alternative in morbidly obese patients. In addition to its efficiency to decrease body weight, it also improves metabolic complications associated to morbid obesity, including dyslipidemia. Although the cholesterol-lowering effect varies with the bariatric procedures, the underlying molecular mechanisms remain poorly defined. This study aims to assess the consequence of both restrictive (sleeve gastrectomy; SG) and malabsorptive (Roux-en-Y gastric bypass; RYGB) procedures on cholesterol metabolism in mice. Ten-week-old C57BL6/J males were fed with a high-fat diet for 8-14 weeks before sleeve or RYGB surgery. SG has a modest and transient effect on plasma cholesterol levels, linked to a reduction in food intake. In contrast, modified RYGB led to a sustained ≈35% reduction in plasma cholesterol concentrations with a drastic increase in fecal cholesterol output. Mechanistically, RYGB exerts a synergystic effect on cholesterol metabolism by inducing the trans-intestinal cholesterol efflux and reducing the intestinal cholesterol absorption. In mice, RYGB, but not sleeve, strongly favors plasma cholesterol elimination by concomitantly increasing trans-intestinal cholesterol excretion and by decreasing intestinal cholesterol absorption. Our models open new perspective for deciphering the hypocholesterolemic effects of bariatric procedures.

Evaluation of coffee ground as a feedstuff in practical diets for olive flounder Paralichthys olivaceus

A 10-week feeding trial was carried out to investigate the feasibility of using spent coffee ground (CG) as a potential feed ingredient for olive flounder. Growth, feed utilization, body composition and antioxidant enzyme activity were examined. A control diet was formulated and three other diets were prepared to contain 5, 10 or 15% CG (designated as Con, CG5, CG10 and CG15, respectively) by replacing for wheat flour. At the end of the feeding trial, fish fed the CG5 diet exhibited significantly (P <0.05) higher growth performance than those fed the control diet. Also, fish fed the CG10 diet had a comparable growth to that of the control group, but further increase of dietary CG inclusion level to 15% resulted in significant decrease of growth performance. Fish fed the CG15 diet showed significantly lower feed efficiency and protein efficiency ratio than other treatments. Significantly lower muscle protein content was observed in fish fed CG15 diet compared to the control. Significant reduction in plasma cholesterol concentration was found in fish fed CG15 diet compared to control. No significant changes were found in alkyle and superoxide radicals scavenging activities of plasma, muscle and liver among dietary treatments. Also, liver total protein, total antioxidant capacity, catalase and glutathione peroxidase activities were not significantly influenced by dietary inclusion of CG. According to these results, we concluded that CG can be included up to 10% in the diet for olive flounder without any adverse effects on growth, feed utilization and antioxidant enzyme activity.

Evaluation of Coffee Ground as a Feedstuff in Practical Diets for Olive Flounder Paralichthys olivaceus

A 10-week feeding trial was carried out to investigate the feasibility of using spent coffee ground (CG) as a potential feed ingredient for olive flounder. Growth, feed utilization, body composition and antioxidant enzyme activity were examined. A control diet was formulated and three other diets were prepared to contain 5, 10 or 15% CG (designated as Con, CG5, CG10 and CG15, respectively) by replacing for wheat flour. Two hundred forty fish (<TEX>$104{\pm}0.7g/fish$</TEX>) were allotted to 12 circular tanks of 400 L capacity at a density of 20 fish per tank and fed the experimental diets twice daily. At the end of the feeding trial, fish fed the CG5 diet exhibited significantly (P < 0.05) higher growth performance than those fed the control diet. Also, fish fed the CG10 diet had a comparable growth to that of the control group, but further increase of dietary CG inclusion level to 15% resulted in significant decrease of growth performance. Fish fed the CG15 diet showed significantly lower feed efficiency and protein efficiency ratio than other treatments. Significantly lower muscle protein content was observed in fish fed CG15 diet compared to the control. Significant reduction in plasma cholesterol concentration was found in fish fed CG15 diet compared to control. No significant changes were found in alkyle and superoxide radicals scavenging activities of plasma, muscle and liver among dietary treatments. Also, liver total protein, total antioxidant capacity, catalase and glutathione peroxidase activities were not significantly influenced by dietary inclusion of CG. According to these results, we concluded that CG can be included up to 10% in the diet for olive flounder without any adverse effects on growth, feed utilization and antioxidant enzyme activity.

Associations of ApoAI and ApoB-containing lipoproteins with AngII-induced abdominal aortic aneurysms in mice.

Dyslipidemia is implicated in abdominal aortic aneurysms (AAAs) in humans and angiotensin (Ang) II-infused mice. This study determined effects of major lipoprotein classes on AngII-induced AAAs using multiple mouse strains with dietary and pharmacological manipulations. Western diet had minor effects on plasma cholesterol concentrations and the low incidence of AngII-induced AAAs in C57BL/6J mice. Low incidence of AAAs in this strain was not attributed to protection from high-density lipoprotein, because apolipoprotein (apo) AI deficiency did not increase AngII-induced AAAs. ApoAI deletion also failed to alter AAA occurrence in hypercholesterolemic mice. Low-density lipoprotein receptor-/- mice fed normal diet had low incidence of AngII-induced AAAs. Western diet feeding of this strain provoked pronounced hypercholesterolemia because of increased apoB-containing lipoproteins with attendant increases of atherosclerosis in both sexes, but AAAs only in male mice. ApoE-deficient mice fed normal diet were modestly hypercholesterolemic, whereas this strain fed Western diet was severely hypercholesterolemic because of increased apoB-containing lipoprotein concentrations. The latter augmented atherosclerosis, but did not change the high incidence of AAAs in this strain. To determine whether reductions in apoB-containing lipoproteins influenced AngII-induced AAAs, ezetimibe was administered at a dose that partially reduced plasma cholesterol concentrations to ApoE-deficient mice fed Western diet. This decreased atherosclerosis, but not AAAs. This ezetimibe dose in ApoE-deficient mice fed normal diet significantly decreased plasma apoB-containing lipoprotein concentrations and reduced AngII-induced AAAs. ApoB-containing lipoproteins contribute to augmentation of AngII-induced AAA in male mice. However, unlike atherosclerosis, AAA occurrence was not correlated with increases in plasma apoB-containing lipoprotein concentrations.

Abstract 358: Targeting of Heparin Binding EGF-like Growth Factor (HB-EGF) Efficiently Inhibits Atherosclerosis

Objective: Heparin-binding EGF-like growth factor (HB-EGF) is a receptor ligand that regulates inflammatory gene expression in the human aortic endothelial cells. In this study, we examined the effects of targeting HB-EGF using an antisense oligonucleotide (ASO) in the development of atherosclerosis. Methods and Results: Control and HB-EGF ASOs were injected intraperitoneally (i.p.; weekly; Dose: 50 mg/kg/wk) for 12 weeks into LDLR deficient mice fed a fat-enriched diet (21% fat; 0.2% cholesterol). Compared with the control ASO injected group (N=13), the HB-EGF ASO injected group (N=15) had efficiently reduced atherosclerosis in the arch of aorta (p&lt;0.0001). The HB-EGF ASO also significantly reduced plasma cholesterol concentration (p = 0.0397). We observed that the VLDL was consistently reduced in all HB-EGF ASO injected mice tested. In liver tissue, the HB-EGF ASO induced significant downregulation of gene expressions of the sterol synthetic pathway as determined by a microarray and DAVID functional analysis (adjusted p = 5.5 x 10-9)). The HB-EGF ASO also induced lipid droplet accumulation in liver tissues as determined by histological analysis with liver tissue sections. Conclusions: This study indicates that HB-EGF is a key mediator for atherosclerosis and the targeting of HB-EGF is an efficient approach to inhibit lesion formation in the aorta. Downregulation of the sterol synthesis pathway and reduction of VLDL particles in the blood may contribute to the protective effects of HB-EGF ASO.

Effects of a Stanol-Enriched Yogurt on Plasma Cholesterol Levels

Plant stanols have been recommended in combination with individualized dietary interventions to reduce plasma cholesterol concentrations. Even though yogurt is consumed in high quantities in Turkey, it is unclear whether yogurts with plant stanols will reduce high cholesterol levels in a Turkish population. We designed this study to settle this issue. We investigated the effect of plant stanols in yogurt, combined with the traditional Mediterranean diet (TMD), in subjects with high lipid levels. 100 patients were included: 50 in the intervention group and 50 in the control group. Neither the subjects nor the control group were taking any medication for cholesterol. The intervention group received 100 mls of stanol-enriched yogurt, while the control group received the same amount of yogurt without plant stanols. All subjects maintained TMD. Total cholesterol and LDL cholesterol levels decreased significantly in the stanol group (12.9%, 14.9%, respectively). In the control group, a slight decrease in LDL cholesterol (3.3%) was observed. The changes in total and LDL cholesterol between the two groups were significantly different (p=0.01). Intensive dietary intervention with the addition of plant stanols results in a clinically relevant reduction of total and LDL cholesterol in patients with high lipid levels.

Xanthohumol ameliorates atherosclerotic plaque formation, hypercholesterolemia, and hepatic steatosis in ApoE‐deficient mice

Xanthohumol (XN), a prenylated antioxidative and anti-inflammatory chalcone from hops, exhibits positive effects on lipid and glucose metabolism. Based on its favorable biological properties, we investigated whether XN attenuates atherosclerosis in western-type diet-fed apolipoprotein-E-deficient (ApoE⁻/⁻) mice. XN supplementation markedly reduced plasma cholesterol concentrations, decreased atherosclerotic lesion area, and attenuated plasma concentrations of the proinflammatory cytokine monocyte chemoattractant protein 1. Decreased hepatic triglyceride and cholesterol content, activation of AMP-activated protein kinase, phosphorylation and inactivation of acetyl-CoA carboxylase, and reduced expression levels of mature sterol regulatory element-binding protein (SREBP)-2 and SREBP-1c mRNA indicate reduced lipogenesis in the liver of XN-fed ApoE⁻/⁻ mice. Concomitant induction of hepatic mRNA expression of carnitine palmitoyltransferase-1a in ApoE⁻/⁻ mice-administered XN suggests increased fatty acid beta-oxidation. Fecal cholesterol concentrations were also markedly increased in XN-fed ApoE⁻/⁻ mice compared with mice fed western-type diet alone. The atheroprotective effects of XN might be attributed to combined beneficial effects on plasma cholesterol and monocyte chemoattractant protein 1 concentrations and hepatic lipid metabolism via activation of AMP-activated protein kinase.

Leptin treatment inhibits the progression of atherosclerosis by attenuating hypercholesterolemia in type 1 diabetic Ins2+/Akita:apoE−/− mice

AimsThe impact of leptin deficiency and its replacement in T1D remain unclear in the context of dyslipidemia and atherosclerosis. The current study has investigated the physiologic role of leptin in lipid metabolism and atherosclerosis in T1D. Methods and resultsThe present study has employed Ins2+/Akita:apoE−/− mouse model that spontaneously develops T1D, hypercholesterolemia, and atherosclerosis. At age 13 weeks, diabetic Ins2+/Akita:apoE−/− mice showed leptin deficiency by ∼92% compared with nondiabetic Ins2+/+:apoE−/− mice. From 13 weeks to 25 weeks of age, diabetic Ins2+/Akita:apoE−/− mice were treated with low-dose leptin (at 0.4 μg/g body weight daily). Leptin treatment diminished food intake by 22–27% in diabetic mice without affecting body weight and lean mass throughout the experiment. Importantly, leptin therapy substantially reduced plasma cholesterol concentrations by ∼41%, especially in LDL fractions, in diabetic Ins2+/Akita:apoE−/− mice. Moreover, leptin therapy decreased atherosclerotic lesion in diabetic mice by ∼62% comparable to that seen in nondiabetic mice. In addition, leptin restored repressed expression of hepatic sortilin-1, a receptor for LDL clearance, and reversed altered expression of several hepatic genes involved in lipogenesis and cholesterol synthesis characteristic of diabetic mice. These findings were accompanied by normalization of reduced hepatic expression of Irs1 and Irs2 mRNA as well as their protein levels, and improved hepatic insulin-receptor signaling. ConclusionsThe present findings suggest that leptin administration may be useful to improve dyslipidemia and reduce atherosclerosis-related cardiovascular disease in human subjects with T1D.

Time of ingestion relative to meal intake determines gastrointestinal responses to a plant sterol–containing yoghurt drink

Plant sterol (PS)-enriched food products are known to reduce plasma cholesterol concentrations by inhibiting the absorption of dietary and biliary cholesterol. The physiological responses induced by food intake in the gastrointestinal tract are all important factors in determining the overall effect of PS. The aim of this study was therefore to assess the effect of timing of consumption of a plant sterol (PS)-containing yoghurt drink relative to meal ingestion on gastric emptying (GE) of the drink and gallbladder (GB) volume. This is a randomized, single-centre, controlled study with crossover design in 12 healthy male volunteers. Three treatments were tested; a 100mL PS yoghurt drink (labeled with 1,000mg acetaminophen) was consumed 45min prior to, during and 45min after a solid meal. Plasma samples were taken, and gallbladder volumes were measured at baseline and at regular intervals during a 6-h study period. When consumed before the consumption of a meal, the yoghurt drink exhibited fast GE. The solid meal intake caused a significant contraction of the gallbladder. Consumption of the PS drink before the meal had no significant effect on GB volume as compared to baseline and compared to during and after meal consumption. The PS-containing drink, which empties fast from the stomach, does not sufficiently trigger gallbladder contraction without co-ingestion of a solid meal and in consequence does not induce the necessary physiological changes needed to allow PS to exhibit their effect on inhibiting cholesterol absorption.

Ezetimibe: its novel effects on the prevention and the treatment of cholesterol gallstones and nonalcoholic Fatty liver disease.

The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1), an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD) in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD.

Bile Acid Sequestrants: Glucose-Lowering Mechanisms

Bile acids are not only intestinal detergents, but also act as signaling molecules to control bile acid and metabolic homeostasis. By binding to the nuclear receptor farnesoid X receptor (FXR) or the membrane receptor TGR5, bile acids regulate lipid, glucose, and energy metabolism. The removal of bile acids from the enterohepatic cycle by orally administered sequestrants, nonabsorbable resins that complex bile acids in the intestinal lumen, is an effective treatment to reduce plasma cholesterol concentrations in dyslipidemia. In diabetic patients, sequestrants further lower hyperglycemia, and are thus useful in glycemic control. Here, we review the signaling pathways involved in the glucose-regulatory function of bile acids and our current understanding of the mechanisms behind the glucose-lowering effect of bile acid sequestrants.

Effects of Fermented Garlic Powder on Production Performance, Egg Quality, Blood Profiles and Fatty Acids Composition of Egg Yolk in Laying Hens

The effects of fermented garlic powder on production performance, egg quality, blood profiles and fatty acid composition of egg yolk in laying hens were studied in a 35-d experiment. Two-hundred and forty (ISA brown) layers aged 41 weeks were randomly allocated into the following four treatments: i) CON (basal diet); ii) G1 (CON+fermented garlic powder 1.0%); iii) G2 (CON+fermented garlic powder 2.0%) and iv) G3 (CON+fermented garlic powder 3.0%). There were no differences (p>0.05) among treatments in egg production, egg weight, eggshell breaking strength and eggshell thickness throughout the whole experimental period. However, yolk height was increased significantly (p 0.05). There was a significant (p<0.05) reduction in plasma cholesterol concentration when the dietary level of fermented garlic powder was increased from 0.0 to 3.0%. The levels of saturated fatty acids (SFA) were significantly decreased (p<0.05) in response to G2 and G3 while monounsaturated fatty acids (MUFA) were higher (p<0.05) in G2 and G3 treatment groups than in CON and G1. Compared with other treatments, polyunsaturated fatty acids (PUFA) and PUFA:SFA ratio were higher (p<0.05) in G3. In conclusion, this study demonstrated that addition of fermented garlic powder reduced plasma cholesterol concentration and did not cause adverse effects on production performance. Moreover, addition of 3.0% garlic powder decreased SFA but increased PUFA and PUFA:SFA ratio in egg yolk.

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.

Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in 'high-dimensional' biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of 'omic' technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based "cocktails" that target specific metabolic pathways to gain maximal cholesterol reductions.