Lower Plasma Lipid Research Articles

Kajian Potensi Kayu Manis dan Teh sebagai Pangan Antidiabetes

Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Type 2 Diabetes Mellitus (T2DM) can be controlled by healthy food and adequate physical activities. Some foods can be used for diabetes control such as cinnamon and tea. This paper determined to study cinnamon and tea researches as an antidiabetic food. All researches about cinnamon and tea as an antidiabetic were collected. It was found that cinnamon ( Cinnamomum burmanii Blume) and tea ( Camelia sinensis L) have many health potentials, such as antioxidants, antibacterial, antidiabetic. Cinnamon shows the ability to lower fasting blood glucose, HbA1c, and plasma lipids; altered postprandial glucose patterns, increased antioxidants and decreased plasma inflammatory markers. In the other hand, tea as the second most consumed drinks in the world could preventing or controlling diabetes with decrease digestive enzyme and intestinal GLUT activity, decrease gluconeogenesis gene expression, increase insulin sensitivity, and protect beta pancreatic. Tea can prevent the risk of T2DM disease if consumed as much as 3 cups per day. It was concluded that both foods can be used to control type 2 diabetes mellitus if consumed in an adequate amount.

Low Energy Availability, Plasma Lipids, and Hormonal Profiles of Recreational Athletes

Black, K, Slater, J, Brown, RC, and Cooke, R. Low energy availability, plasma lipids, and hormonal profiles of recreational athletes. J Strength Cond Res 32(10): 2816-2824, 2018-It has been postulated that low energy availability (LEA) impacts bone health, hormonal concentrations, and cardiovascular function. This study describes the lipid levels, hormonal profiles, and nutrient intakes of recreationally active adults at risk of LEA compared with those not at risk. Thirty-eight women who meet or exceed the New Zealand guidelines for physical activity participated. Each participant completed an online questionnaire including the Low Energy Availability in Females questionnaire (LEAF-Q), demographic questions, and daily exercise to determine energy expenditure. Participants also provided a weighed 3-day diet record, a blood sample analyzed for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and cortisol, and a saliva sample analyzed for testosterone. Body composition was assessed using bioelectrical impedance. Those classed as at risk of LEA according to the LEAF-Q showed very likely lower energy availability (at risk: mean, 36.3 [95% confidence interval, 30.8-41.7] kcal·kg·FFMd vs. not at risk: mean, 47.5 [95% CI, 39.5-55.4] kcal·kg·FFMd) and lower calcium intakes (mean, 847 [95% CI, 695-998] mg, vs. mean, 1488 [95% CI, 690-2,286] mg). Those at risk also had a likely small lower T3 concentration of 1.78 (SD: 0.36) nmol·L compared with 2.01 (SD: 0.53) nmol·L for those not at risk. These data suggest that recreationally active female subjects classed as at risk of LEA according to the LEAF-Q also have lower energy availability as determined by diet records and exercise diaries. The results also suggests that those at risk of LEA have reductions in T3, and their low energy intake, in addition to a low calcium intake, could put them at an increased risk of poor bone health.

UJI AKTIVITAS HIPOLIPIDEMIK EKSTRAK ETANOL HERBA KROKOT (Portulaca oleracea L.) PADA TIKUS OBESITAS DENGAN PARAMETER TRIGLISERIDA

Hypolipidemics a drug used to lower plasma lipid levels in the blood. This study aimed to examine the hypolipidemic activity of ethanol extract of purslane herb ( Portulaca oleracea L.) against the triglyceride level reduction in obese mice. The purslane herb contains omega-3, flavonoids and hight ascorbic acid as a lowering of triglyceride levels in the blood. This study used 15 malerats divided into 5 groups. Group I (negative control) was given Na.CMC 1%, group II (positive control) was given Gemfibrozil, group III, IV, and V were given ethanol extract of purslane herb with dose of 100 mg/kgBW, 200mg/kgBW, and 300 mg/kgBW as therapy group. All the administration were done orally once a day for 16 days. The measurement of triglyceride level was performed on early triglycerides before induction, after induction and after therapy. Before therapy, the rats were given hight-calorie diet. The results showed that the ethanol extract of purslanes herb has activity as hypolipidemic in lowering trygliseride level in obese mice. From the statistic result of One-Way ANOVA followed by LSD test, it can be concluded that the ethanol extract of purslane herb of the dose 100 mg/kgBW provide the most effective hypolipidemic activity that triglyceride level is not significantly different from positive control group (p>0,05).

Hyperlipidemic Inhibitory Effects of Phellinus pini in Rats Fed with a High Fat and Cholesterol Diet

This study evaluated the in vitro and in vivo hypolipidemic effects of the medicinal mushroom Phellinus pini. The methanol extract (ME) of the fruiting body of Ph. pini was active against pancreatic lipase and cholesterol esterase with 99.14% and 67.23% inhibited activity at 1.0 mg/mL, respectively. It also inhibited 81.81% and 55.33% of α-glucosidase and α-amylase activities, respectively, at 2.0 mg/mL. Hyperlipidemia as induced by feeding rats with a high fat and cholesterol diet (HFC). HFC supplemented with a 5% fruiting body powder of Ph. pini (HFC + PhP) significantly reduced plasma total cholesterol, low-density lipoprotein cholesterol, and triglycerides in rats compared with HFC. The reduced levels were comparable to rats fed the normal control diet (NC). The atherogenic index of HFC + PhP rats was significantly lower than that of the HFC rats. The excretion of fecal total lipid and cholesterol in the HFC + PhP rats was significantly higher than those in the NC and HFC rats. Histopathological examinations demonstrated scant deposition of lipids in the liver of rats fed HFC + PhP. The dietary supplementation with the fruiting body powder provided natural plasma lipid and glucose lowering effects in experimental rats without adverse effects on the plasma biochemical parameters and liver function related enzyme activities. Therefore, the hypolipidemic effects of Ph. pini may be due to the inhibitory effects on pancreatic lipase, cholesterol esterase, α-glucosidase, and α-amylase, and excretion of excess lipids and cholesterol in the feces.

Antioxidant activity and Hypolipidemic effect of Ficus carica leaf and twig extracts in Triton WR-1339-induced hyperlipidemic mice

BACKGROUND/AIM: The hypolipidemic potential of both leaf and twig extracts of Ficus carica on experimental hyperlipidaemia induced by Triton WR-1339, in Swiss albino mice was investigated. In addition, the phenolic, flavonoid and anthocyanin contents of these extracts and their antioxidant activities were determined. These properties may have a synergistic effect on hyperlipidaemia. MATERIALS AND METHODS: Leaf and twig samples of F. carica were harvested and collected. The study of antioxidant activity of phenolic compounds was determined by the radical DPPH*, ABTS*+ and FRAP assays. The experimental design was carried out using acute oral toxicity study and Triton model hyperlipidaemia on Swiss albino adult male mice. The animals were observed continuously during the 14 days of the study for any physical signs of toxicity. On the 15th day, the animals were sacrificed by decapitation under anesthesia and the organs were observed for macroscopic pathological lesions. Hyperlipidaemia was induced in the mice by a single intravenous (iv) injection of Triton WR 1339 (300 mg/kg body weight), and the antihyperlipidemic effect of each extract, studied at 150 and 300 mg, was tested by gavage. After 24 hours of administration, serum from blood samples was used to estimate the various parameters of the lipid profile namely TC, TG, LDL and HDL. RESULTS: The results of the phenolic and flavonoid compounds of Ficus carica leaves and twigs varied from 12.84 to 19.78 mg gallic acid equivalents (GAE) and 5.02 to 9.72 mg EQ/g dry matter, respectively. The scavenging activity (IC50) against the radical DPPH* and ABTS*+ varied from 346.2 to 461.38 μg/mL and 288.3 to 369.01 μg/mL for twigs and leaves respectively, and from 50.82 to 54.2 μg/mL for FRAP assay. The acute toxicity study showed no mortality and clinical signs of toxicity in the tested doses. The LD50 value of extracts of twigs and leaves of Ficus carica is greater than 5000 mg/kg. The results revealed that the administration of Ficus carica (FC) leaf and twig extracts resulted in a significant (p < 0.05) decline in levels of serum triglycerides, total cholesterol, LDL-c, and VLDL-c, while the serum high-density lipoprotein cholesterol was significantly increased. The decrease rate of the lipid parameters differs significantly (p < 0.05) from the leaf and twig extracts and depends also on the administered dose. CONCLUSION: Ficus carica leaf and twig extracts may contain compounds able to lower plasma lipid concentrations, could contribute significantly to the total antioxidant properties and be beneficial in the treatment of hyperlipidaemia.

Plasma lipid lowering effect by a novel chia seed based nutraceutical formulation

Atherosclerotic cardiovascular diseases (ASCVD) are preferential targets of preventive medicine partially through therapies to improve atherogenic lipid profiles. The aim of the present work was to test a novel nutraceutical formulation (CSN) for its potential effects on plasma triglyceride levels of healthy subjects with moderate dyslipidemia. A cohort of 52 individuals were administered daily, for 8 weeks, with four gastro-resistant capsules of CSN, each one containing 500 mg of cryo-micronized chia seeds and 15 mg of vitamin E, according to a single centre, randomized, placebo controlled, 16 weeks trial. Data showed the following mean lipid changes: triglycerides, −27.5% (P = .0095); total cholesterol, −8.0% (P = .0019); High Density Lipoprotein cholesterol, +5.7% (P = .0042); Low Density Lipoprotein cholesterol, −10.2% (P = .0021). CSN may be regarded as a novel complementary and/or alternative safe remedy with clinical relevance in the primary cardiovascular disease prevention.

MicroRNA-30c reduces plasma cholesterol in homozygous familial hypercholesterolemic and type 2 diabetic mouse models

High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce the risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein production; however, this is associated with steatosis. We previously showed that microRNA (miR)-30c lowers diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe−/− mice. Here, we tested the effect of miR-30c on plasma lipids, transaminases, and hepatic lipids in different mouse models. Hepatic delivery of miR-30c to chow-fed leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) hypercholesterolemic and hyperglycemic mice reduced cholesterol in total plasma and VLDL/LDL by ∼28% and ∼25%, respectively, without affecting triglyceride and glucose levels. And these mice had lower plasma transaminases and creatine kinase activities than controls. Moreover, miR-30c significantly lowered plasma cholesterol and atherosclerosis in Western diet-fed Ldlr−/− mice with no effect on plasma triglyceride, glucose, and transaminases. In these studies, hepatic lipids were similar in control and miR-30c-injected mice. Mechanistic studies showed that miR-30c reduced hepatic microsomal triglyceride transfer protein activity and lipid synthesis. Thus miR-30c reduced plasma cholesterol in several diet-induced and diabetic hypercholesterolemic mice. We speculate that miR-30c may be beneficial in lowering plasma cholesterol in different metabolic disorders independent of the origin of hypercholesterolemia.

Effects of Ginger on LDL-C, Total Cholesterol and Body Weight

Hyperlipidemia whether it is primary or secondary to take high lipid-content diets can cause coronary artery disease. This condition can be prevented and treated by allopathy related drugs like vitamin B3, and statins. As these drugs have potential to develop severe side effects, many cardiologists have approved utilization of medicinal herbs to control hyperlipidemia. We selected its hypolipidemic and weight lost effects in primary and secondary hyperlipidemic patients. Type of Research study: It was placebo-controlled study. Area of research: Research was conducted in Jinnah hospital, Lahore, Pakistan. Duration of study: It was three months, from January 2014 to June 2014. Materials, methods and results: Already well understood, clearly explained written consent was taken from sixty hyperlipidemic patients age range from 18 to 70 years. Both gender male and female patients were enrolled. Patients were randomly divided in two groups 30 patients were on drug ginger pasted-powder advised to take 5 grams in divided doses with their normal diet for the period of three months. Thirty patients were on placebo pastedwheat powder, with same color as of ginger powder, advised to take 5 grams in divided doses with their normal diet for the period of three months. Their base line lipid profile and body weight was recorded at start of treatment and were advised to come for check-up, fortnightly. When duration of study was over, their lipid profile and body weight was measured and compared statistically with pre-treatment values. Three months treatment with 5 grams of Ginger decreased LDL-cholesterol 17.41%, total-cholesterol 8.83% and body weight 2.11%. When compared with placebo group, all changes in mentioned parameters were significant bio-statistically. Conclusion: It was concluded from results of study that active ingredients of ginger lower plasma lipids and body weight significantly, eventually preventing development of coronary artery disease in primary and secondary hyperlipidemic patients.

Systemic mastocytosis associates with cardiovascular events despite lower plasma lipid levels

Background and aimsMast cells have been implicated in the development and progression of atherosclerosis in animal models and human autopsy studies. However, it is unknown whether long-term exposure to excess of mast cells is associated with cardiovascular disease (CVD) in humans. Our objective was to compare the prevalence of CVD and cardiovascular risk factors in patients with systemic mastocytosis (SM) and controls. MethodsIn 50 patients with SM and 50 age and sex matched controls, the history of CVD and presence of cardiovascular risk factors were assessed. Carotid ultrasound was performed to assess carotid intima-media thickness (C-IMT) and plaques presence. ResultsCVD events were more prevalent in SM patients compared to controls (20% vs. 6%, p = 0.04). The prevalence of C-IMT and carotid plaques was similar between patients with SM and controls. In multivariate analysis, CVD events were significantly associated with SM (OR 7.0 (95% CI 1.3–37.6), p = 0.02) and hypertension (OR 9.5 (95% CI 1.9–48.7), p = 0.01). The prevalence of diabetes, hypertension, obesity and smoking was similar between the two groups. Total cholesterol and LDL-C levels were significantly lower in SM patients than in the control group. (5.1 ± 1.1 vs. 5.9 ± 0.9 mmol/l, p < 0.05 and 2.9 ± 0.8 vs. 3.5 ± 0.7 mmol/l, p < 0.05, respectively). ConclusionsDespite lower plasma total cholesterol and LDL-C, the prevalence of CVD is higher in patients with SM compared to healthy controls. Beyond the setting of SM, this study can be considered as a proof of concept study, indicating the contribution of mast cells to CVD in humans.

Kappaphycus alvarezii as a Food Supplement Prevents Diet-Induced Metabolic Syndrome in Rats.

The red seaweed, Kappaphycus alvarezii, was evaluated for its potential to prevent signs of metabolic syndrome through use as a whole food supplement. Major biochemical components of dried Kappaphycus are carrageenan (soluble fiber ~34.6%) and salt (predominantly potassium (K) 20%) with a low overall energy content for whole seaweed. Eight to nine week old male Wistar rats were randomly divided into three groups and fed for 8 weeks on a corn starch diet, a high-carbohydrate, high-fat (H) diet, alone or supplemented with a 5% (w/w) dried and milled Kappaphycus blended into the base diet. H-fed rats showed symptoms of metabolic syndrome including increased body weight, total fat mass, systolic blood pressure, left ventricular collagen deposition, plasma triglycerides, and plasma non-esterified fatty acids along with fatty liver. Relative to these obese rats, Kappaphycus-treated rats showed normalized body weight and adiposity, lower systolic blood pressure, improved heart and liver structure, and lower plasma lipids, even in presence of H diet. Kappaphycus modulated the balance between Firmicutes and Bacteroidetes in the gut, which could serve as the potential mechanism for improved metabolic variables; this was accompanied by no damage to the gut structure. Thus, whole Kappaphycus improved cardiovascular, liver, and metabolic parameters in obese rats.

Implications of Sortilin in Lipid Metabolism and Lipid Disorder Diseases.

The present review provides a summary of recent evidence of sortilin expression, function, and regulation and its implications in lipid metabolism and development of lipid disorder diseases. As a member of the vacuolar protein sorting 10 protein (Vps10p) receptor family, sortilin mediates intracellular trafficking of diverse endogenous or exogenous protein substrates between the trans-Golgi network (TGN) and plasma membrane compartments. Recent studies reveal that sortilin regulates the expression of lipid genes, plasma lipid level, and the development of lipid disorder diseases. Sortilin promotes atherogenesis by regulating hepatic very low density lipoprotein (VLDL) secretion and plasma lipid level and subsequently macrophage lipid accumulation. Sortilin deficiency is caused by accelerated proteasome degradation under insulin resistance conditions and is thereby implicated in the hyperlipidemia of type 2 diabetes mellitus (T2DM). Sortilin facilitates hepatic cholesterol accumulation by inhibiting hepatic cholesterol catabolism, which promotes the development of nonalcoholic fatty liver disease (NAFLD). Sortilin plays an important role in lipid metabolism and represents a promising therapeutic target for lipid disorder diseases.

THE CCR7+ PDGFRA+ CELL POPULATION IS INCREASED IN REGRESSING ATHEROSCLEROTIC PLAQUES

Atherosclerosis is characterized by the accumulation of lipids, cells and fibers in the arterial wall. Atherosclerotic plaques form in regions of low blood flow, whereas vessels exposed to high shear stress remain lesion-free. We created a surgical mouse model, arteriovenous fistula (AVF), which increases blood flow in the brachiocephalic artery (BCA) specifically, without altering serum lipid levels. LDLR KO mice were placed on a high-fat diet (HFD). Control mice were sacrificed at week 12. Sham and AVF surgery was performed at week 12 and mice were kept on a HFD for a further 1-4 weeks. We found that high blood flow is beneficial and leads to a significant ∼50% regression of BCA plaque size in AVF mice compared with Controls, by week 4. We performed flow cytometry to characterize the different cell populations within Sham and AVF plaques. At day 7 after surgery, there was no difference in macrophage (F4/80+) or dendritic cell (CD11c+) content between Sham and AVF. However, we found a significant, 4-fold increase in the total number of CD45-/CCR7+/PDGFRa+ cells in the BCA plaques of AVF mice vs Shams (p < 0.01). No such change was observed in the aortic sinus plaques of AVF or Shams. CCR7 was previously found to be overexpressed in regressing plaques upon an abrupt lowering of plasma lipids, but in CD45+ cells. In our model, plasma lipids remained high and CCR7+ cells instead expressed PDGFRa, a perivascular and multi-lineage differentiation marker. This cell population also expressed mesenchymal stem cell markers (CD90, CD44, CD34). Our data point to an unexpected increase in the CD45-/CCR7+/PDGFRa+ cell population in the early plaque regression process. They suggest that mesenchymal-type cells may promote regression in plaques exposed to high blood flow.

Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy

BackgroundDuchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles.MethodsTo test the blood vessel contribution to muscle damage in DMD, mdx4cv mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets. Ambulatory function and heart function (via echocardiogram) were assessed at 4 and 7 months of age. After sacrifice, muscle histology and aortic staining were used to assess muscle pathology and atherosclerosis development, respectively. Plasma levels of total cholesterol, high-density lipoprotein (HDL), triglycerides, and creatine kinase (CK) were also measured.ResultsAlthough there was an increase in left ventricular heart volume in mdx-ApoE mice compared to that in mdx mice, parameters of heart function were not affected. Compared with wild-type and ApoE-null, only mdx-ApoE KO mice showed significant ambulatory dysfunction. Despite no significant difference in plasma CK, histological analyses revealed that elevated plasma lipids in chow- and Western diet-fed mdx-ApoE mice was associated with severe exacerbation of muscle pathology compared to mdx mice: significant increase in myofiber damage and fibrofatty replacement in the gastrocnemius and triceps brachii muscles, more reminiscent of human DMD pathology. Finally, although both ApoE and mdx-ApoE groups displayed increased plasma lipids, mdx-ApoE exhibited atherosclerotic plaque deposition equal to or less than that of ApoE mice.ConclusionsSince others have shown that lipid abnormalities correlate with DMD severity, our data suggest that plasma lipids could be primary contributors to human DMD severity and that the notoriously mild phenotype of mdx mice might be attributable in part to their endogenously low plasma lipid profiles. Hence, DMD patients may benefit from lipid-lowering and vascular-targeted therapies.

P 228 - Green Rooibos Extract improves plasma lipid profile and oxidative status in diabetic non-human primates

Rooibos,a shrub-like leguminous bush endemic to South Africa, is traditionally used as a herbal tea. Unfermented (green) rooibos presents with a much higher polyphenol content, in particular aspalathin which constitutes a major metabolically bioactive compound. Recent studies, both in vitro and ex vivo, highlighted an enhanced glucose uptake effect of aspalathin, associated with increased GLUT 4 translocation to the plasma membrane via AMPK activation. In high fat fed mice, aspalathin also showed a plasma lipid lowering effect. In the present study, we evaluated the effect of 4 weeks of supplementation (90 mg/kg body weight t.i.d) with a pharmaceutical grade aspalathin-enriched green rooibos extract containing ca. 12.8% aspalathin, on gluco-lipidic and oxidative indexes in high fat diet-induceddiabetic and normal non-human primates (Chlorocebus aethiops). Diabetic models were characterized by glucose intolerance and increased total cholesterol and LDL. Moreover, decreased plasma CoQ10 and increased oxidative status were associated with higher levels of oxLDL. Green rooibos supplementation of the diabetic animals significantly improved all listed indices, highlighting the potentialities of this natural extract in modulating some risk factors associated with cardiovascular disease associated with type 2 diabetes.

Abstract 205: Inhibition of Angiopoietin-Like 3 Expression is a Potential Mechanism of Activation of Lipoprotein Lipase and of Lipid Lowering by Metformin

Dyslipidemias associated with primary lipid disorders or secondary to abnormal glucose metabolism are commonly seen metabolic disorders in the clinic. Of special interest is the diabetic dyslipidemia and its growing prevalence. Interestingly, metformin, a commonly used anti-diabetic drug also has potent lipid lowering activity. However, the mechanisms associated with this metformin activity are poorly understood. A key protein regulating the plasma lipid homeostasis is the enzyme lipoprotein lipase (LPL) which is found lining the capillary endothelium in tissue capillary beds. LPL hydrolyses the core triglycerides (TGs) of chylomicrons and very-low density lipoprotein (VLDL). Angiopoietin-like 3 (ANGPTL3), a secretory protein derived from liver, inhibits the lipolytic activity of LPL, resulting in an increase in plasma TGs. We investigated whether metformin regulates LPL and in effect plasma lipids, via regulation of ANGPTL3 in the liver. A single dose (150mg/kg) treatment of metformin for twenty-four hours in mice resulted in an increase in the LPL activity in plasma. Since metformin is frequently used in type 2 diabetes which is characterized by insulin resistance, a condition compounded by dietary fatty acids, we studied the relationship between metformin and ANGPTL3 in a human liver cell line treated with palmitic acid. Treatment with palmitic acid mimicked the conditions of insulin resistance in the liver and elevated the expression of ANGPTL3 in the liver which was inhibited by co-treatment with metformin. Gene and protein expression assays revealed a potent inhibition of ANGPTL3 expression and secretion from the hepatocytes upon treatment with metformin. We examined the role of sirtuin 1 (SIRT1)/adenosine monophosphate activated kinase (AMPK) in the metformin regulation of ANGPTL3 and observed that even though activation of SIRT1/AMPK axis inhibited the expression of ANGPTL3, metformin inhibition of ANGPTL3 was independent of SIRT1/AMPK as revealed by pharmacological inhibition and gene knockdown approaches. Our studies suggest that a potential mechanism of lipid lowering activity of metformin is the inhibition of expression of ANGPTL3, which results in an increase in LPL activity and a lowering of plasma lipids.

Abstract 582: The CCR7+ PDGFRa+ Cell Population is Increased in Regressing Atherosclerotic Plaques

Introduction: Atherosclerosis is characterized by the accumulation of lipids, cells and fibers in the arterial wall. Atherosclerotic plaques form in regions of low blood flow, whereas vessels exposed to high blood flow remain lesion-free. We created a surgical mouse model, arteriovenous fistula (AVF), which increases blood flow in the brachiocephalic artery (BCA) specifically, without altering serum lipid levels. Methods &amp; Results: LDLR KO mice were placed on a high-fat diet (HFD). Control mice were sacrificed at week 12. Sham and AVF surgery was performed at week 12 and mice were kept on a HFD for a further 1-4 weeks. We found that high blood flow is beneficial and leads to a significant ~50% regression of BCA plaque size in AVF mice compared with Controls, by week 4. We performed flow cytometry to characterize the different cell populations within Sham and AVF plaques. At day 7 after surgery, there was no difference in macrophage (F4/80+) or dendritic cell (CD11c+) content between Sham and AVF. However, we found a significant, 4-fold increase in the total number of CD45-/CCR7+/PDGFRa+ cells in the BCA plaques of AVF mice vs Shams (p&lt;0.01). No such change was observed in the aortic sinus plaques of AVF or Shams. CCR7 was previously found to be overexpressed in regressing plaques upon an abrupt lowering of plasma lipids, but in CD45+ cells. In our model, plasma lipids remained high and CCR7+ cells instead expressed PDGFRa, a perivascular and multi-lineage differentiation marker. This cell population also expressed mesenchymal stem cell markers (CD90, CD44, CD34) and CD68. Conclusion: Our data point to an unexpected increase in the CD45-/CCR7+/PDGFRa+ cell population in the early plaque regression process. They suggest that mesenchymal-type cells may promote regression in plaques exposed to high blood flow.

Abstract 577: MicroRNA-30c Reduces Plasma Cholesterol in Different Hypercholesterolemic and Hyperglycemic Mouse Models

High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein assembly and secretion; however, this is associated with steatosis. We have shown that microRNA-30c (miR-30c) reduces Western diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe -/- mice with no obvious adverse effects by reducing hepatic lipoprotein production and lipid synthesis. Here, we tested the effect of miR-30c on plasma lipids, transaminases and hepatic lipids in five different mouse models. Hepatic delivery of miR-30c reduced MTP activity but did not affect plasma cholesterol, triglyceride and glucose in chow-fed C57Bl6J and streptozotocin-induced diabetic, normolipidemic mice. However, hepatic delivery of miR-30c to chow fed leptin deficient ( ob/ob ) and leptin receptor deficient ( db/db ) hypercholesterolemic and hyperglycemic type 2 diabetic mice reduced cholesterol in total plasma and VLDL/LDL by ~ 28%and ~ 25%, respectively, without affecting phospholipid, triglyceride and glucose levels. Interestingly, these mice had lower plasma transaminases and creatine kinases indicating possible beneficial effects. Mechanistic studies showed that miR-30c reduced hepatic MTP activity and lipid synthesis. Moreover, miR-30c significantly lowered plasma cholesterol and atherosclerosis in Western-diet fed low density lipoprotein receptor knockout mice with no effect on plasma triglyceride, glucose and transaminases, suggesting that miR-30c can be a potential therapeutic agent for homozygous familial hypercholesterolemia. In all these studies, hepatic lipid levels were similar in control and miR-30c injected mice. These studies indicate that miR-30c reduces plasma cholesterol in diet-induced and diabetic hyperholesterolemic mice but not in normocholesterolemic mice. Thus, miR-30c may be beneficial in lowering plasma cholesterol in different metabolic disorders independent of the origin of hypercholesterolemia.

Moringa leaf powder modulate reverse cholesterol transport without changing plasma lipids in guinea

Leaves from the plant Moringa Oleifera have been found to improve insulin resistance, reduce inflammation and lower plasma lipids in several animal models. The polyphenols/flavonoids present in Moringa leaves (ML) appear to be the bioactive components responsible of these beneficial effects. In this study we hypothesized that Moringa leaves (ML) would improve lipid profile by modulating the size and number of lipoprotein subfractions (large, medium or small) and affect reverse cholesterol transport (RCT) in guinea pigs. Twenty four 3‐month old male Hartley guinea pigs, were given a hypercholesterolemic diet with 0.25% cholesterol and were randomly allocated to either one of three Moringa groups (n=8/group): control (0% ML), Low Moringa (10% ML) or High Moringa (15% ML), corresponding to a daily intake of 0, 3 or 4.5 g ML/day. Animals consumed these diets for 6 weeks. Macro and micronutrients were adjusted for all diets, the only difference being the flavonoids and polyphenols present in ML. After sacrifice, blood was collected and plasma was obtained by centrifugation. Plasma was aliquoted to measure total, LDL and HDL cholesterol, triglycerides, glucose, and insulin. VLDL, LDL and HDL subfractions concentrations and size were measured by nuclear magnetic resonance. Lecithin cholesterol acyltransferase (LCAT) and cholesteryl ester protein (CETP) activities, major regulators of RCT, were also measured by fluorometric methods. Unexpectedly, no changes in plasma lipids, glucose or insulin were observed among groups. However both ML groups had lower concentrations of the medium HDL, which has been postulated to be pro‐atherogenic. Values were: 0.56 μmol/L for control, 0.11 ± 0.21 μmol/L for 10% ML and 0.21 ± 0.13 μmol/L for 15% ML groups. Further LCAT activity was increased by 55% (p&lt; 0.05) by ML intake while CETP activity was not different among groups. These results suggest a potential role of ML in modulating RCTSupport or Funding InformationTaif University, Saudi Arabia

The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model.

BackgroundA growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood.MethodsIn an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder.ResultsA similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs.ConclusionIn a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period.

Fructose during pregnancy provokes fetal oxidative stress: The key role of the placental heme oxygenase-1.

One of the features of metabolic syndrome caused by liquid fructose intake is an impairment of redox status. We have investigated whether maternal fructose ingestion modifies the redox status in pregnant rats and their fetuses. Fructose (10% wt/vol) in the drinking water of rats throughout gestation, leads to maternal hepatic oxidative stress. However, this change was also observed in glucose-fed rats and, in fact, both carbohydrates produced a decrease in antioxidant enzyme activity. Surprisingly, mothers fed carbohydrates displayed low plasma lipid oxidation. In contrast, fetuses from fructose-fed mothers showed elevated levels of plasma lipoperoxides versus fetuses from control or glucose-fed mothers. Interestingly, a clearly augmented oxidative stress was observed in placenta of fructose-fed mothers, accompanied by a lower expression of the transcription factor Nuclear factor-erythroid 2-related factor-2 (Nrf2) and its target gene, heme oxygenase-1 (HO-1), a potent antioxidant molecule. Moreover, histone deacetylase 3 (HDAC3) that has been proposed to upregulate HO-1 expression by stabilizing Nrf2, exhibited a diminished expression in placenta of fructose-supplemented mothers. Maternal fructose intake provoked an imbalanced redox status in placenta and a clear diminution of HO-1 expression, which could be responsible for the augmented oxidative stress found in their fetuses.