Reduced Lipid Levels Research Articles

Serum Lipid Profile in Nigerian Patients with Ischaemic Cerebrovascular Accident

Ischaemic Cerebrovascular Accident (CVA) has been shown to be associated with abnormal lipid profile (dyslipidaemia) as a risk factor. There is paucity of data regarding this in this environment hence this study. In this study, a total number of 63 subjects were recruited comprised of 33 patients with cerebrovascular accident (stroke) and 30 apparently healthy volunteers as control. A complete lipid profile which included Total serum Cholesterol (TC), serum Triglyceride (TG), High Density Lipoprotein cholesterol (HDL-c) and Low Density Lipoprotein cholesterol (LDL-c) were assayed for both patients and controls. The lipid profile was determined using standard methods. The TC for both patients and control were 212±53 and 196±46 mg/dL respectively, TG for both patients and controls were 159±9 and 79±13 mg/dL respectively, HDL-c was 55±9 mg/dL for patients and 61±7 mg/dL for controls and LDL-c was 151±34 mg/dL for patients and 117±51 mg/dL for control subjects. TC, TG and LDL-c were higher in the ischaemic CVA patients than the controls; however only TG showed a significant increase while HDL-c although not significant was lower than control. The study therefore showed that ischaemic CVA is associated with hypercholesterolaemia, hypertriglyceridaemia and high LDL-cholesterol. We thus suggest preventive and management strategies that will reduce lipid levels (TC, TG and LDL) and enhance HDL-cholesterol in Nigeria patients that are prone to or diagnosed of ischaemic CVA.

New targets and developments in lipoproteins control

New targets and developments in lipoproteins control Giuseppe Danilo Norata1–31Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 2Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy; 3The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UKAbstract: Statins provide a very effective approach in reducing plasma cholesterol levels and cardiovascular risk. However, the proportion of patients who fail to achieve desirable plasma lipid levels ranges from 16%–53%, worldwide. This percentage reaches up to 80% in patients with familial hypercholesterolemia. Additionally, many patients are unable to tolerate statins, particularly at the highest approved dose level. New treatments that aggressively reduce lipid levels in patients with severe hypercholesterolemia, or those unable to reach their lipid targets, are therefore required. The most promising approaches in this context, such as inhibitors of the synthesis of apolipoprotein B (apoB) containing lipoproteins (apoB silencing or microsomal triglyceride transfer protein [MTP] inhibition) or proprotein convertase subtilisin/kexin type 9 (PCSK9) blockers, all decrease low-density lipoprotein (LDL) extensively. Increasing low levels of high-density lipoprotein (HDL) cholesterol via cholesteryl ester transfer protein inhibitors or apolipoprotein A-1 (ApoA-1) inducers and improving their quality with HDL or ApoA-1 mimetics represent also important options. Drugs affecting HDL, however, may not be all alike and require adequate scrutiny of the mechanisms involved. Until we have a better understanding of these issues, further LDL lowering in high-risk patients represents the soundest approach.Keywords: apolipoproteins, lipids, lipoprotein classes, hypercholesterolemia, synthesis, LDL lowering

Juvenile hormone and insulin suppress lipolysis between periods of lactation during tsetse fly pregnancy

Tsetse flies are viviparous insects that nurture a single intrauterine progeny per gonotrophic cycle. The developing larva is nourished by the lipid-rich, milk-like secretions from a modified female accessory gland (milk gland). An essential feature of the lactation process involves lipid mobilization for incorporation into the milk. In this study, we examined roles for juvenile hormone (JH) and insulin/IGF-like (IIS) signaling pathways during tsetse pregnancy. In particular, we examined the roles for these pathways in regulating lipid homeostasis during transitions between non-lactating (dry) and lactating periods. The dry period occurs over the course of oogenesis and embryogenesis, while the lactation period spans intrauterine larvigenesis. Genes involved in the JH and IIS pathways were upregulated during dry periods, correlating with lipid accumulation between bouts of lactation. RNAi suppression of Forkhead Box Sub Group O (FOXO) expression impaired lipolysis during tsetse lactation and reduced fecundity. Similar reduction of the JH receptor Methoprene tolerant (Met), but not its paralog germ cell expressed (gce), reduced lipid accumulation during dry periods, indicating functional divergence between Met and gce during tsetse reproduction. Reduced lipid levels following Met knockdown led to impaired fecundity due to inadequate fat reserves at the initiation of milk production. Both the application of the JH analog (JHA) methoprene and injection of insulin into lactating females increased stored lipids by suppressing lipolysis and reduced transcripts of lactation-specific genes, leading to elevated rates of larval abortion. To our knowledge, this study is the first to address the molecular physiology of JH and IIS in a viviparous insect, and specifically to provide a role for JH signaling through Met in the regulation of lipid metabolism during insect lactation.

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Effects of Dietary Quercetin on Growth Performance, Serum Lipids Level and Body Composition of Tilapia (Oreochromis Niloticus)

This trial was conducted to investigate the effects of supplementary quercetin on growth performance, serum lipids levels and whole fish body composition in tilapia (Oreochromis niloticus). Four hundred fish were randomly divided into five treatment groups with four replicates in each group and 20 fish in each replicate. The dietary quercetin levels of the five treatment groups were: 0 (control group), 200, 400, 800, and 1600 mg/kg, respectively; the trial period was 7 weeks. Compared with the control group, specific growth rate and condition factor of quercetin groups were improved significantly (P<0.05). No significant differences in feed conversion rate and survival rate were found between the control group and all quercetin groups (P>0.05). The triglyceride concentration in serum was decreased significantly with the increasing levels of quercetin supplementation (P<0.05), while the high-density lipoprotein cholesterol concentration was increased significantly by the supplementation of quercetin (P<0.05). The significant difference of low-density lipoprotein cholesterol concentration was found only between control group and highest dietary quercetin level group (P<0.05). The levels of moisture, crude protein and crude lipid of whole fish body were significantly affected by the supplementation of quercetin (P<0.05), the ash levels of all groups were similar (P>0.05). In conclusion, we demonstrated a promotion of growth performance and the reduction of lipid levels in serum and whole fish body with the supplementation of quercetin.

Effects of Fat and Cinnamon Feeding on Adiponectin after Rat Injection with Dexamethasone

Chronically excessive numbers of glucocorticoids are known to induce insulin resistance, which is possibly involved in impairing the insulin signaling in liver, muscle, and adipose tissues. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia ,all of these features are shared by the condition of insulin resistance .Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance [7]. Fatty acid composition in the diet is another mechanism implicated in the development of insulin resistance [6]. Several environmental factors, including high-fat diet, are reported to activate the functioning of the hypothalamus-pituitary-adrenal axis [HPA]. Frequently evoked HPA-axis secretes excessive amount of cortisol [21] and elevated cortisol level is implicated in the development of entire spectrum of the metabolic syndrome, including insulin resistance, visceral obesity and dyslipidemia as well as the kinds of [21]. Cinnamon contains biologically active substances that have demonstrated insulin-mimetic properties. In vitro [3] and in vivo [1, 20] studies have shown that cinnamon enhances glucose uptake by activating insulin receptor kinase activity, autophosphorylation of the insulin receptor, and glycogen synthase activity. Other recent studies have demonstrated the ability of cinnamon to reduce lipid levels in fructose-fed rats, potentially via inhibiting hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity [2]. Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone,playing a central role in glucose and lipid metabolism [7] Furthermore, adiponectin levels are inversely associated with visceral adiposity [15]. Moreover, adiponectin has been reported to exhibit anti-atherosclerotic and anti-inflammatory effects [17,16].

Analysis of ovary-specific genes in relation to egg maturation and female nutritional condition in the mosquitoes Georgecraigius atropalpus and Aedes aegypti (Diptera: Culicidae)

Analysis of the reproductive physiology of anautogenous mosquitoes at the molecular level is complicated by the simultaneity of ovarian maturation and the digestion of a blood meal. In contrast to anautogenous mosquitoes, autogenous female mosquitoes can acquire greater nutrient stores as larvae and exhibit higher ovarian production of ecdysteroids at adult eclosion. These features essentially replace the role of a blood meal in provisioning the first batch of eggs and initiating egg development. To gain insight into the process of ovary maturation we first performed a transcript analysis of the obligatory autogenous mosquito Georgecraigius atropalpus (formerly Ochlerotatus atropalpus). We identified ESTs using suppressive subtractive hybridization (SSH) of transcripts from ovaries at critical times during oogenesis in the absence of blood digestion. Preliminary expression studies of genes such as apolipophorin III (APO) and oxysterol binding protein (OSBP) suggested these genes might be cued to female nutritional status. We then applied our findings to the medically important anautogenous mosquito Aedes aegypti. RNAi-based analyses of these genes in Ae. aegypti revealed a reduction in APO transcripts leads to reduced lipid levels in carcass and ovaries and that OSBP may play a role in overall lipid and sterol homeostasis. In addition to expanding our understanding of mosquito ovarian development, the continued use of a comparative approach between autogenous and anautogenous species may provide novel intervention points for the regulation of mosquito egg production.

Antihyperlipidemic Effect of Methanolic Extract from Opuntia joconostle Seeds in Mice Fed a Hypercholesterolemic Diet

The purpose of this study was to evaluate the hypolipidemic effect of a methanolic extract from Opuntia joconostle seeds fed to mice in a hypercholesterolemic diet. Acute toxicity of the methanolic extract was investigated by an established method. Phenolic composition and antioxidant activity were determined by high-performance liquid chromatography and DPPH, respectively. The total phenolic content of Opuntia joconostle seeds was 47.85 ± 1.29 mg gallic acid equivalents/g dry weight. The main phenolic compounds were identified as quercetin, rutin, and cafeic acid. Percent inhibition of DPPH⁺ was 49.76 ± 0.49 %. The oral LD₅₀ for the methanolic extract from the Opuntia joconostle seeds was >5,000 mg/kg BW. Mice fed a hypercholesterolemic diet for six days exhibited significantly (P ≤ 0.001) higher plasma lipid levels than mice fed a normal diet. Remarkably, supplementation with methanolic extract from Opuntia joconostle at doses of 1, 2, and 5 g/kg body weight significantly (P ≤ 0.001) prevented the increase in total cholesterol, low-density lipoprotein cholesterol, triglycerides level, and atherogenic index. Similar concentrations of the HDL cholesterol were observed in both treated and control groups. A significant dose-dependent reduction in lipid levels was noted for treated groups compared to the hypercholesterolemic group. We attribute this result to the seeds' phenolic composition. This methanolic extract has potential to be included in short-term hypercholesterolemia treatment regimens as it exhibits hypolipidemic activity with no apparent toxic manifestations.

Advagraf vs. Prograf as Immunosuppressive Therapy in De Novo Renal Transplant Immunosuppressive Therapy: A Single Centre Experience

Introduction: The prevention of allograft rejection a foremost challenge for the clinicians involved in transplant. Among the regimens aimed to suppress transplant recipient immune response against the graft, tacrolimus represents a milestone of immunosuppressive therapy. The formulation of Prograf capsules requires twice-a-day administration. Advagraf is a recently developed slow-release once-a-day oral formulation of tacrolimus, with similar efficacy and safety profile of 12-hour formulation (Prograf). It been shown that poor compliance is one relevant factor associated with graft loss: once-daily dosing can contribute to improved patient adherence. Few data are currently available on Advagraf use in clinical practice, especially as early immunosuppressive therapy in transplants. We therefore evaluated the efficacy and pharmacokinetics of single-dose formulation compared to the traditional Prograf twice-daily dosing in de novo renal transplants. Methods: During 2009-2010, 30 renal transplant recipients were recruited: 15 of them (Advagraf group), receiving single-dose tacrolimus (0.2-0.3 mg/kg/day) were compared with 15 patients (Prograft group) treated with tacrolimus in twice-a-day administration (0.2 mg/kg/day administered every 12 hours in two divided doses). In both groups, tacrolimus was associated with mycophenolate mofetil/mycophenolic acid and steroids. Tacrolimus blood levels and the adjusted dose based on tacrolimus trough whole blood concentrations were recorded at 3rd, 5th, 7th, 10th, 15th postoperative day and at discharge. Results: The groups did not differ significantly in terms of patient characteristics and drug efficacy. Drug blood levels tended to be lower in the first weeks post-transplant, particularly in Advagraf-treated patients who required higher drug doses (0.3 mg/kg/day); afterwards blood concentrations reached a stable level, with a consequent necessity to reduce Advagraf dosage (0.2-0.3 mg/kg/day after the first month). The incidence of rejection was comparable in the two groups (1 steroid-sensitive acute rejection in each group). Concerning side effects, a similar percentage of patients in the groups experienced neurological disorders (headache, tremor) (33.3% of Advagraf-treated patients vs. 26.7% of Prograf-treated patients). Likewise, the occurrence of posttransplant diabetes (according to ADA criteria) did not differ significantly between Advagraf and Prograf group (20% vs. 26.7% of the patients respectively), and the incidence of systemic infections (CMV, polyomavirus) was identical (6.7% vs. 6.7%), In both groups, arterial hypertension worsened in those patients of both groups who had a clinical history of hypertension during dialysis (33.3% vs. 33.3%), while no new-onset hypertension was found in patients without history of hypertension. In line with literature in patients receiving Advagraf displayed reduced lipid levels. Conclusions: This study suggests that in de novo kidney transplant, single-dose formulation of tacrolimus has a similar short-term efficacy compared with twice-a-day administration. The data also highlight the necessity to increase Advagraf dosage in the first week post-transplant to achieve effective therapeutic levels (11-15 ng/ml). This observation is in agreement with literature and can be explained by the once daily morning administration which inevitably leads to a lower baseline C0 value when compared with the twice-daily dosing regimen. Both formulations showed analogous efficacy as well as side effects. An emerging finding is the reduction of lipid profile with a considerable importance for cardiovascular risk.

Formulation design and evaluation of a self-microemulsifying drug delivery system of lovastatin

Self-microemulsifying drug delivery system (SMEDDS) of lovastatin was aimed at overcoming the problems of poor solubility and bioavailability. The formulation strategy included selection of oil phase based on saturated solubility studies and surfactant and co-surfactant screening on the basis of their emulsification ability. Ternary phase diagrams were constructed to identify the self-emulsifying region. Capryol 90 (20%) as oil, Cremophore RH40 (40%) as surfactant and Transcutol P (40%) as co-surfactant were concluded to be optimized components. The prepared SMEDDS was characterized through its droplet size, zeta potential, emulsification time, rheological determination and transmission electron microscopy. The optimized formulation exhibited 94% in vitro drug release, which was significantly higher than that of the drug solution. In vivo studies using the Triton-induced hyperlipidemia model in Wistar rats revealed considerable reduction in lipid levels compared to pure lovastatin. The study confirmed the potential of lovastatin SMEDDS for oral administration.

Behavioral Counseling Interventions to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults: U.S. Preventive Services Task Force Recommendation Statement

Update of the 2003 and 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statements on behavioral counseling to promote a healthful diet and physical activity in adults without preexisting cardiovascular disease (CVD) or its risk factors. The USPSTF reviewed new evidence on whether counseling interventions relevant to primary care for physical activity or a healthful diet modify self-reported behaviors; intermediate physiologic outcomes (for example, reduced lipid levels, blood pressure, weight, and body mass index and increased glucose tolerance); and cardiovascular morbidity and mortality in adults without known CVD, hypertension, hyperlipidemia, or diabetes. General adult population without a known diagnosis of hypertension, diabetes, hyperlipidemia, or CVD. Although the correlation among healthful diet, physical activity, and the incidence of CVD is strong, existing evidence indicates that the health benefit of initiating behavioral counseling in the primary care setting to promote a healthful diet and physical activity is small. Clinicians may choose to selectively counsel patients rather than incorporate counseling into the care of all adults in the general population. Issues to consider include other risk factors for CVD, a patient's readiness for change, social support and community resources that support behavioral change, and other health care and preventive service priorities. Harms may include the lost opportunity to provide other services that have a greater health effect. This is a grade C recommendation.

Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy

ObjectiveWe evaluated the long-term effects of rosuvastatin and simvastatin on insulin sensitivity and secretion in patients with well-controlled type 2 diabetes. MethodsAfter a 3 weeks run-in, 27 eligible patients were randomly assigned to receive either rosuvastatin 20 mg daily (Group 1) or simvastatin 20 mg daily (Group 2) for 6 months; thereafter they were switched to the other treatment for additional 6 months. Patients were recruited among individuals attending the outpatient service of the Diabetology Unit of the “Policlinico Tor Vergata” University Hospital, Rome, Italy. Serum lipids, glucose and insulin, glycated hemoglobin, C-reactive protein, TNF-α, leptin, adiponectin, insulin sensitivity by euglycemic–hyperinsulinemic clamp, β-cells function by HOMA-β were assessed at months 0, 6 and 12. Additionally, endothelial function was assessed by use of the brachial artery reactivity technique. ResultsBesides marked reduction in lipid levels, glycated hemoglobin significantly increased from baseline after 12 months in both Group 1 (+0.8 ± 0.2%, p < 0.001) and Group 2 (+0.9 ± 0.3%; p < 0.001). Similar trends were observed for fasting glucose in both groups. No changes in insulin sensitivity were detected throughout the study, whereas HOMA-β significantly decreased from baseline after 12 months in both Group 1 (−21.9%, p < 0.01) and Group 2 (−38.9%; p < 0.001). In addition, both treatments similarly decreased C-reactive protein and leptin, as well as improved endothelial function. No changes in anthropometric measures were observed. ConclusionsIn well-controlled type 2 diabetic patients both rosuvastatin and simvastatin significantly impaired glycemic control and insulin secretion, without affecting insulin sensitivity.

AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis

The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism.

Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging

Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that β-adrenergic receptor (β-AR) levels and β-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Here we investigated whether age-associated increases in β-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the β-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of β1- and β2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of β-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the β-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenol-mediated hepatic fat accumulation; thus β-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic β-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for β-adrenergic blockers in preventing or retarding the development of hepatic steatosis.

Alteration of lipids and the transcription of lipid-related genes in myelodysplastic syndromes via a TP53-related pathway

Myelodysplastic syndromes (MDS) are clonal stem cell diseases of the bone marrow characterized by abnormalities in maturation of hematopoietic cells of all lineages. MDS patients frequently have lower lipids and high rates of apoptosis and p53 (TP53) expression. An association between the reduced lipids in MDS and the expression of lipid-related genes was sought. We further evaluated whether 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGcoAR) and low-density lipoprotein receptor (LDL-R) are regulated by TP53 invivo and invitro. Gene expression was measured using real-time reverse transcription polymerase chain reaction on RNA extracted from bone marrow and peripheral blood from eight newly diagnosed MDS patients and eight controls and from mice livers. Serum lipid profile was measured using colorimetric enzymatic procedures. Total- and LDL cholesterol were lower in MDS patients in comparison to controls (p = 0.04 and p = 0.01, respectively). HMGcoAR messenger RNA increased in peripheral blood and bone marrow of MDS patients compared to controls (p = 0.04 and p = 0.01, respectively). LDL-R messenger RNA was higher only in the peripheral blood of MDS patients (p = 0.05). Comparable results were obtained invivo. The transcription of these genes correlates with TP53 activation as documented by p21 messenger RNA elevation, a surrogate for TP53 activation and by using TP53 temperature-sensitive cells treated with adriamycin. To conclude, an association between reduced lipids in MDS and expression of HMGcoAR and LDL-R genes was documented. The transcription of these genes can be regulated by TP53.

Regulatory effects of curcumin on lipid accumulation in monocytes/macrophages

Recent evidence suggests potential benefits from phytochemicals and micronutrients in protecting against atherosclerosis and inflammation, but the molecular mechanisms of these actions are still unclear. Here, we investigated whether the dietary polyphenol curcumin can modulate the accumulation of lipids in monocytes/macrophages. Curcumin increased the expression of two lipid transport genes, the fatty acids transporter CD36/FAT and the fatty acids binding protein 4 (FABP4/aP2; P < 0.05), leading to increased lipid levels in THP-1 and RAW264.7 monocytes and macrophages (P < 0.05). To investigate the molecular mechanisms involved, we assessed the activity of Forkhead box O3a (FOXO3a), a transcription factor centrally involved in regulating several stress resistance and lipid transport genes. Curcumin increased FOXO3a-mediated gene expression by twofold (P < 0.05), possibly as a result of influencing FOXO3a phosphorylation and nuclear translocation. The curcumin derivative, tetrahydrocurcumin (THC), with similar chemical antioxidant activity as curcumin, did not show any measurable effects. In contrast to the in vitro results, curcumin showed a trend for reduction of lipid levels in peritoneal macrophages in LDL receptor knockout mice fed a high fat diet for 4 months, suggesting additional regulatory mechanisms in vivo. Thus, the up-regulation of FOXO3a activity by curcumin could be a mechanism to protect against oxidant- and lipid-induced damage in the inflammatory cells of the vascular system.

Impact of probiotics, prebiotics and synbiotics on lipid metabolism in humans

Public health strategies for reducing the risk of coronary heart disease have focused on lowering plasma lipids, particularly cholesterol levels, with recent studies also highlighting triacylglycerol (TAG) as an important modifiable risk factor. One approach is to supplement the diet with probiotics, prebiotics or synbiotics. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Putative health benefits include improved resistance to gastrointestinal infections, reduction in lipid levels and stimulation of the immune system. Prebiotics are selectively fermented dietary components that are aimed at improving host health through selective fermentation by the gut microbiota, such as bifidobacteria and lactobacilli. Animal studies have shown prebiotics to markedly reduce circulating TAG and to a lesser extent cholesterol concentrations, with favourable but inconsistent findings with respect to changes in lipid levels in human studies. Here we provide an overview of the effects, and possible mechanisms, of probiotics, prebiotics and synbiotics (combination of a probiotic and prebiotic) on circulating lipeamia in humans.

An intervention study in obese mice with astaxanthin, a marine carotenoid – effects on insulin signaling and pro-inflammatory cytokines

Astaxanthin (ASX), a xanthophyll carotenoid from the marine algae Hematococcus pluvialis, has anti-obesity and insulin-sensitivity effects. The specific molecular mechanisms of its actions are not yet established. The present study was designed to investigate the mechanisms underlying the insulin sensitivity effects of ASX in a non-genetic insulin resistant animal model. A group of male Swiss albino mice was divided into two and fed either a starch-based control diet or a high fat-high fructose diet (HFFD). Fifteen days later, mice in each dietary group were divided into two and were treated with either ASX (6 mg kg(-1) per day) in olive oil or olive oil alone. At the end of 60 days, glucose, insulin and pro-inflammatory cytokines in plasma, lipids and oxidative stress markers in skeletal muscle and adipose tissue were assessed. Further, post-receptor insulin signaling events in skeletal muscle were analyzed. Increased body weight, hyperglycemia, hyperinsulinemia and increased plasma levels of tumor necrosis factor-α and interleukin-6 observed in HFFD-fed mice were significantly improved by ASX addition. ASX treatment also reduced lipid levels and oxidative stress in skeletal muscle and adipose tissue. ASX improved insulin signaling by enhancing the autophosphorylation of insulin receptor-β (IR-β), IRS-1 associated PI3-kinase step, phospho-Akt/Akt ratio and GLUT-4 translocation in skeletal muscle. This study demonstrates for the first time that chronic ASX administration improves insulin sensitivity by activating the post-receptor insulin signaling and by reducing oxidative stress, lipid accumulation and proinflammatory cytokines in obese mice.

Alterations In Lipid Profile Of Patients With Advanced Cervical Cancer

Background The changes in lipid profile have long been associated with cancer because lipids play key role in maintenance of cell integrity. Aims. The study evaluated alterations in plasma lipid profile in patients with advanced squamous cervical cancer. Materials And Method This hospital-based study included 30 cervical cancer patients, with 30 controls. Plasma lipids including: Total cholesterol (TC), Low Density Lipoprotein cholesterol (LDL ), High Density Lipoprotein cholesterol C (HDL ) and triglycerides (TAG) were analyzed by spectrophotometric kits. C Student's t-test was performed to compare mean values of the parameters. Results A significant decrease in plasma total cholesterol, HDLC and triglycerides was observed in cervical cancer patients as compared to the controls. The LDL lipid fraction was however higher in the cases than in the C controls. Also there was direct relationship between reduced lipid levels and cervical cancer progression, this was statistically significant. Conclusion The lower levels of plasma cholesterol and other lipid constituents in patients might be due to low levels of antioxidants which is a common finding among cancer patients, however this would have to be confirmed by evaluating the anti-oxidant levels of these patients. There is also the need to conduct a study with a much larger sample size. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in cervical cancer patients as a means of monitoring and evaluating such patients.Key Words: Lipid profile, cancer, cervix, spectophotometry, Benin City.

Administration of Rosmarinic Acid Reduces Cardiopathology and Blood Pressure Through Inhibition of p22phox NADPH Oxidase in Fructose-Fed Hypertensive Rats

Rosmarinic acid (RA), a caffeic acid ester, has insulin-sensitizing and antioxidant effects in high fructose-fed model of insulin resistance (IR). This study investigated whether RA supplementation prevents cardiac abnormalities and hypertension in fructose-fed rats (FFR). Rats fed with fructose diet (60 g/100 g) for 60 days exhibited metabolic abnormalities and rise in plasma and cardiac lipids and whole body IR. The levels of cardiac antioxidants and plasma ferric reducing antioxidant power were significantly reduced in FFR concomitant with increased levels of lipid peroxidation and protein oxidation products. A significant rise in troponin T, creatine kinase-MB, aspartate transaminase, and lactate dehydrogenase in plasma of FFR was noted. RA supplementation to FFR (10 mg/kg from the 16th day) significantly improved insulin sensitivity, reduced lipid levels, oxidative damage, and the expression of p22phox subunit of nicotinamide adenine dinucleotide phosphate reduced oxidase, and prevented cardiac hypertrophy. Fructose-induced rise in blood pressure was also lowered by RA through decrease in endothelin-1 and angiotensin-converting enzyme activity and increase in nitric oxide levels. Histology revealed a reduction in myocardial damage in RA-supplemented FFR. These findings suggest that RA acts as a vasoactive substance and a cardioprotector through its antioxidant property. Thus, RA may be useful in reducing the cardiovascular risk associated with IR.