Decreased Plasma Lipid Research Articles

Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples

BackgroundPersistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain. ObjectiveWithin longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations. MethodsFor 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of hexachlorobenzene (HCB), dichlorodiphenyl-dichloroethylene (p,p'-DDE), dioxin-like (DL) polychlorinated biphenyl congeners (PCB-118 and PCB-156), and non-dioxin like (NDL-PCB: PCB-74, -99, -138 -153, −170, −180, −183 and PCB-187) were analyzed twice (baseline and follow-up, 9–20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p'-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n = 306). ResultsPOPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p < 0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p'-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p < 0.05 for all POPs).In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments. DiscussionThe association between POPs and T2D was confirmed, but an indication that individuals body fat history might influence POP-T2D associations weakens the epidemiological support for a causal association. It also warrants studies based on other exposure metrics than biomonitoring. In addition, we note that a cross-sectional design overestimates the ORs if T2D cases have successfully intervened on weight and/or blood lipids, as changes in these factors cause changes in POPs.

Dual‐Stimuli‐Responsive Gut Microbiota‐Targeting Berberine‐CS/PT‐NPs Improved Metabolic Status in Obese Hamsters

AbstractGut dysbiosis has been found to be involved in the pathogenesis of energy metabolic disorders and might be a new strategy for these ailments. Berberine (BBR), a botanical medicine, shows therapeutic efficacy in patients with metabolic diseases. Numerous reports have shown BBR's modulating effect on gut microbiota, opening a new avenue to understand BBR's mechanism. In this study, a colon‐specific delivery system, BBR‐CS/PT‐NP, is investigated by the assembly of pH/gut microflora dual stimuli‐responsive nanoparticles for enhancing the interaction between BBR and gut microbiota. After oral administration, the delivering system remains stable in the stomach and small intestine, followed by a burst release of BBR after reaching the colon segment rich in intestinal bacteria. The enzymes produced by bacteria degrade the nanoparticle, causing direct exposure of BBR to gut microbiota. In the high fat diet‐induced obese hamsters, BBR‐CS/PT‐NP intervention inhibits weight‐gain and fat deposition, decreases plasma lipids and glucose levels, improves inflammation condition and insulin resistance, alleviates hepatic steatosis, at a level significantly higher than the pure BBR does. The mechanisms might be attributable to the enhanced interaction between BBR and the gut flora. The results provide a novel proof‐of‐concept for drug delivery targeting gut microbiota to ameliorate metabolic disorders.

Bitter Leaves Ethanol Extract (Vernonia amygdalina) Decreases Total Cholesterol Serum Level of Hypercholesterolemic Male Wistar Rats

Hypercholesterolemia is an important risk factors of atherosclerosis. Bitter leaf is believed to have potency in decreasing plasma lipid. The aim of this study is to study the effect of bitter leaf ethanol extract in decreasing total cholesterol serum levels on hypercholesterolemic male Wistar rats. This is a true experimental laboratory study with complete randomized design. Antidyslipidemia effect was tested with HFF induction and Propiltiourasil 0,01% towards 30 rats which were divided into 6 groups: groups I as normal control (standard diet), groups II, III, and IV were given bitter leaf ethanol extract of 100 mg/kgBW, 200 mg/kgBW, and 400 mg/kgBW dose, group V as positive control group with Simvastatin, and group VI as negative with aquades. HFF were given for 14 days then the study was continued for 14 days. The percentage data of the declining total cholesterol levels before and after treatments is analyzed with ANAVA, continued with LSD test. The result between group II, III, and IV with group VI shows a significant difference p&lt;0,01. We concluded bitter leaf ethanol extract can decrease the level of total cholesterol serum of hypercholesterolmic Wistar rats.

Maternal olive oil intake enhances lipid metabolism and lipase activities in offspring of cafeteria diet-induced obese rats

It has long been established that maternal nutritional condition and fatty acid intake during pregnancy and/or lactation may influence the modifications in the individual risk for developing metabolic diseases throughout life, but little is known about the possible role of maternal nutrition before conception. The aim of this study was to investigate the effect of maternal supplementation with olive oil on offspring lipid metabolism under obesogenic conditions. Female Wistar rats were fed control or cafeteria diet which were either supplemented or not supplemented with olive oil (5%) for 2 months before and during gestation. Pregnant rats and their offspring were also fed on similar diet. After overnight fasting, offspring were sacrificed at 1 and 3 month of life. Cafeteria diet led to higher body weight, hyperglycemia and hyperlipidemia, LDL cholesterol, serum Lecithin–cholesterol acyltransferase activity and tissues lipoprotein lipase and hormone-sensitive lipase in offspring. In contrast, adult obese offspring had a lower HDL cholesterol. Olive oil rich-CAF diet decreased plasma lipids, increased HDL cholesterol and up-regulated lipolytic enzyme activities at weaning until adulthood. These data suggest that maternal olive oil may an effective strategy to improving metabolic alterations related to cafeteria diet in offspring.

THE EFFECT OF COENZYME Q10 AND/OR SILYMARIN ON RENALASE GENE EXPRESSION OF CARDIORENAL SYNDROME IN ADULT MALE ALBINO RATS

Background: Therapeutic strategies in cardiorenal syndrome (CRS) should be directed to the cardio-renal connectors like renalase. Coenzyme Q10 (CoQ10) and silymarin are natural anti-oxidant and anti-inflammatory agents. Objectives: Assessing the effect of CoQ10 and/or Silymarin on renalase gene expression in CRS induced by high fructose diet (HFD) in male rats. Patients and Methods: Fifty adult male albino rats of local strain were divided into 5 equal groups and subjected to the following regimens for 8 weeks: Group I: Supplemented orally with 1 ml of 2% aqueous solution of tween 80. Group II: Received HFD in the form of 30% fructose in drinking water. Group III: Received HFD and CoQ10 orally at a dose of 20 mg/kg/day dissolved in 2% tween-80 aqueous solution. Group IV: Received HFD and Silymarin orally at a dose of 200 mg/kg/day dissolved in 2% tween-80 aqueous solution. Group V: Received HFD and both CoQ10 and silymarin in the same regimen as described before. Results: CoQ10 and/or Silymarin significantly decreased plasma lipid profile, cardiac troponin-I, creatinine, malondialdehyde (MDA) & tumor necrosis factor alpha (TNF- α) levels when compared to HFD group. On the other hand, CoQ10 and/or silymarin caused significant increase in plasma catalase level & renalase gene expression in kidney tissue when compared to HFD group. They also improved HFD -induced cardiac and renal fibrosis. Conclusion: CoQ10 and Silymarin induced improvement in HFD-induced CRS as they possessed cardio-protective, reno-protective, hypo-lipidimic, anti-oxidant, anti-inflammatory and anti-fibrotic activities, as well as increased renalase expression.

γ-Pyrone compounds: flavonoids and maltol glucoside derivatives from Herniaria glabra L. collected in the Ternopil region of the Ukraine

The phytochemical investigation of the whole plant extracts of Herniaria glabra L. (Caryophyllaceae) led to the identification and isolation of four known flavonoids, one known and three undescribed maltol derivatives, and benzyl β-gentiobioside. The structures were established by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. For the first time in Herniaria genus, as well as in Caryophylaceae family the presence of apiorutin {quercetin 3-O-[(D-apio-β-d-furanosyl-(1 → 2)-O-[-α-l-rhamnopyranosyl-(1 → 6)]-β-d-glucopyranoside]} and licoagroside B {maltol 3-O-[6-O-(3-hydroxy-3-methylglutaroyl)]-β-d-glucopyranoside} were revealed. Additionally, antioxidant actions of apiorutin, rutin, narcissin (isorhamentin 3-O-β-d-rutinoside) and licoagroside B were assessed in human blood plasma, exposed to the peroxynitrite-induced oxidative stress in vitro. The isolates partly reduced oxidative (oxidation of thiol groups) and nitrative (tyrosine nitration) damage to blood plasma proteins, decreased plasma lipid peroxidation as well as enhanced the non-enzymatic antioxidant capacity of blood plasma. No cytotoxicity of the examined substances towards peripheral blood mononuclear cells was found.

Black Grass Jelly (Mesona Palustris Bl) Effervescent Powder has Anti-Dyslipidemia in High Cholesterol Diet-Fed Rats and Antioxidant Activity

Dyslipidemia that could be affected by hypercholesterol diet is a contributing factor in millions of deaths worldwide and a risk factor for ischemic heart disease and stroke. High soluble fiber diet is used as one of the non-pharmacological treatments to control hypercholesterolemia. Black Grass Jelly (Mesona palustris BL) also known as black cincau has a high soluble fiber content. This study aimed to investigate the effect of black cincau as effervescent powder form (BCEP) for anti-dyslipidemia and also the antioxidant activity. BCEP was orally administered to twenty male dyslipidemia Wistar rats induced with hypercholesterol diet for 3 weeks then plasma lipid profile was measured using enzymatic CHOD-PAP assay. The antioxidant activity also has been identified. Oral administration of 3 different doses of BCEP resulted in lipid profiles by decreasing plasma cholesterol (TC), triacylglycerol (TG), low-density lipoprotein (LDL), and also high-density lipoprotein (HDL) in dyslipidemia rats (α = 0.01). The increasing doses of BCEP revealed that it has a potential effect of decreasing plasma lipid.

Rice Cookie Decreases Plasma and Hepatic Lipid Levels in High-Fat Diet-fed Mice: A Comparison Study with Traditional Western Style Cookies

The lipid-lowering and antioxidant effects of the traditional Korean rice cookie (KRC), dasik, were compared with those of a western style cookie (WSC) in mice fed a high-fat diet (HFD). The KRC or WSC was supplemented to the HFD as 7% of the total calories. The experimental groups (n = 7) were the normal diet group, HFD group, HFD-KRC group, and HFD-WSC group. The plasma and hepatic triglyceride concentrations of the HFD-KRC group were found to be lower than those of the HFD-WSC group as a result of sterol regulatory element-binding protein 1 and fatty acid synthase expression downregulation, and concomitant peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase 1, and acyl-coenzyme A oxidase 1 expression upregulation (p<0.05). The hepatic reactive oxygen species and peroxynitrite levels were also diminished in the HFD-KRC group of mice, whereas their catalase and glutathione peroxidase protein expression levels were higher than those in the HFD and HFD-WSC groups (p<0.05). In conclusion, the lipid-lowering effects and antioxidant property of the KRC were greater than those of the WSC in mice fed a HFD. Thus, the choice of KRCs as a snack would be preferable to choosing WSCs.

Sex Differences in the Hormonal and Metabolic Response to Dietary Protein Dilution.

Consumption of a low-protein, high-carbohydrate diet induces a striking increase in circulating fibroblast growth factor-21 (FGF21), which is associated with improved cardiometabolic health and increased longevity. Increased lifespan during this dietary protein "dilution" has been explained by resource-mediated trade-offs between reproduction and survival, such that fecundity is optimized at a greater relative intake of proteins/carbohydrates. The magnitude of this trade-off is thought to be sex-dependent. In this study, we tested the hypothesis that metabolic responses to dietary protein dilution are likewise dependent on sex. We maintained age-matched adult male and female C57BL/6J mice on isocaloric diets containing 22% fat and differing in the ratio of protein/carbohydrate. The normal protein (NP) control diet contained 18% protein and 60% carbohydrate by kcal. The protein diluted (PD) diet contained 4% protein and 74% carbohydrate. Consistent with previous reports, PD males gained less weight and less fat than did normal protein controls and exhibited both improved glucose tolerance and decreased plasma lipids. In contrast, these metabolic benefits were absent among age-matched females maintained on the same diets. Likewise, whereas circulating FGF21 was increased up to 66-fold among PD male mice, this was substantially blunted among female counterparts. Sex differences in energy balance, glucose control, and plasma FGF21 were reversed upon ovariectomy. Collectively, our findings support that female mice are relatively less sensitive to the metabolic improvements observed following dietary protein dilution. This is accompanied by blunted circulating levels of FGF21 and requires an intact female reproductive system.

Antioxidant defense system in familial hypercholesterolemia and the effects of lipoprotein apheresis

Oxidative stress is thought to play an important role in the pathogenesis of disorders associated with atherosclerosis. Alpha-tocopherol is considered to be an effective lipophilic antioxidant, which protects lipid membranes against peroxidation and thus prevents cell damage by reaction with free radicals. However, measurement of alpha-tocopherol concentration in serum does not reflect the content of α-tocopherol in membranes whereas erythrocyte alpha-tocopherol may be good indicator of antioxidative status. Therefore a simple isocratic reversed phase HPLC method has been developed and validated for the determination of alpha-tocopherol in human erythrocytes in a clinical setting. The content of alpha-tocopherol in human erythrocyte membrane and lipoperoxidation were studied in patients with severe hypercholesterolemia treated by lipoprotein apheresis. The group of hypercholesterolemic patients (n = 14) treated by lipoprotein apheresis was compared to healthy adult normolipidemic controls. After lipoprotein apheresis, the content of in membrane alpha-tocopherol did not change significantly despite decreased tocopherol in serum and lipoprotein fractions. We observed significantly decreased lipoperoxidation as revealed by serum TBARS, representing end products of lipid peroxidation, which increased from third day afterwards and remained significantly higher in comparison to controls until the next LDL-apheresis. We conclude that aggressive lipid lowering procedure with lipoprotein apheresis was associated with favorable transient decrease of lipoperoxidation. Simultaneously the cell membrane bound antioxidative defense mechanisms as reflected by the content of alpha-tocopherol in human erythrocyte membrane where not depressed in spite of its decreased plasma lipid carrier. Another variables involved remain to be investigated.

Effects of high-intensity interval training on body composition, aerobic and anaerobic performance and plasma lipids in overweight/obese and normal-weight young men.

To examine the effects of short high-intensity interval training (HIIT) on body composition, physical performance and plasma lipids in overweight/obese compared to normal-weight young men. Nine overweight/obese and nine normal-weight men (control group) aged 17 to 20 years underwent a HIIT programme three times per week for eight weeks. Body composition, indices of aerobic [maximal aerobic velocity (MAV) and maximal oxygen uptake (VO2max)] and anaerobic [squat jump (SJ), counter-movement jump (CMJ), five-jump test (FJT), 10-m and 30-m sprint] performances, as well as fasting plasma lipids, were assessed in the two groups at PRE and POST HIIT. The HIIT programme resulted in significant reductions in body mass (-1.62%, P=0.016, ES=0.11) and fat mass (-1.59%, P=0.021, ES=0.23) in obese, but not in normal-weight subjects. MAV (+5.55%, P=0.005, ES=0.60 and +2.96%, P=0.009, ES=0.82), VO2max (+5.27%, P=0.006, ES=0.63 and +2.88%, P=0.009, ES=0.41), FJT (+3.63%, P=0.005, ES=0.28 and +2.94%, P=0.009, ES=0.52), SJ (+4.92%, P=0.009, ES=0.25 and +6.94%, P=0.009, ES=0.70) and CMJ (+6.84%, P=0.014, ES=0.30 and +6.69%, P=0.002, ES=0.64) significantly increased in overweight/obese and normal-weight groups, respectively. 30-m sprint time significantly decreased in both groups (-1.77%, P=0.038, ES=0.12 and -0.72%, P=0.030, ES=0.16). Plasma total cholesterol (-11.8%, P=0.026, ES=0.96), LDL cholesterol (-11.9%, P=0.050, ES=0.77) and triglycerides (-21.3%, P=0.023, ES=1.08) significantly decreased in the obese group, but not in the normal-weight group. The eight-week HIIT programme resulted in a slight improvement in physical fitness and a significant decrease in plasma lipids in the obese. Short duration HIIT may contribute to an improved cardiometabolic profile in the obese.

Procalcitonin (PCT) As A Promising Marker For Diagnosis and Differentiation of Bacterial Infections

Background: Bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Early identification of bacterial infection in patients with fever is important for prompt treatment. However, the available parameters such as C-reactive protein (CRP) and leukocyte counts are not very specific. This study was aimed to assess the diagnostic value of procalcitonin (PCT) and cholesterol for bacterial infection in febrile patients. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. Also a decrease in plasma lipids occurs during severe sepsis and has prognostic implications in critical illness. Methods: Review of the medical records of every patient treated between May, 2014 and May, 2015 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT, WBCs, CRP and cholesterol levels were measured at the onset of infection Results: 88 episodes of either GN bacteremia (n = 56) or GP bacteremia (n = 32) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia. TLC, CRP, PCT were significantly increased, while cholesterol was significantly decreased in cases when compared to control group. Conclusion: In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease. Low lipid levels, particularly low Cholesterol, pointed to bacterial infection Reflecting the severity of disease, plasma lipid levels may be a complementary tool in the diagnostic workup of patients with septicemia.

Creatine supplementation decreases plasma lipid peroxidation markers and enhances anaerobic performance in rats

Objective: The study was to investigate the effects of creatine (Cr) supplementation on oxidative stress markers and anaerobic performance in rats.Methods: Sixty-four rats (Wistar) were divided into two groups: C, anaerobic exercised group (n = 32) and Cr, anaerobic exercised group supplemented with creatine (n = 32). Cr supplementation consisted of the addition of 2% Cr monohydrate to the diet. After 28 days, the rats performed acute exercise (6 × 30 seconds of vertical jumps in the water with 30 seconds rest and 50% of total body weight load attached in the back). The animals were euthanized before (pre) and at 0, 2, and 6 hours (n = 8) after acute exercise.Results: Acute exercise induced an increase in plasma malondialdehyde (MDA) and advanced oxidation protein products (AOPP), as well as increased total lipid hydroperoxides and AOPP in gastrocnemius muscle. Cr supplementation inhibited the formation of MDA and lipid hydroperoxides in plasma. However, the antioxidant action of Cr was observed only against AOPP in gastrocnemius muscle. Cr supplementation also increased (P < 0.05) anaerobic performance compared to the C group.Conclusion: Cr supplementation is able to inhibit the increase in plasma lipid peroxidation markers induced by high-intensity and short-duration exercise in rats; equivalent actions, however, were not observed fully in muscle tissue.

Tribbles-1: a novel regulator of hepatic lipid metabolism in humans.

The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target.

Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non-alcoholic fatty liver disease model.

BackgroundIlex latifolia Thunb. (Da Ye Dong Qing) is used for weight loss and for its antidiabetic effects. This study aims to investigate the beneficial effects and potential mechanisms of action of crude triterpenoid saponins (CTS) from I. latifolia in a mouse model of high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD).MethodsMale C57BL/6 mice (n = 50), were arbitrarily divided into five groups (n = 10 in each group): a control group, HFD group, simvastatin group (10 mg/kg/day), and two CTS treatment groups (100 and 200 mg/kg/day). All mice except those in the control group were fed an HFD for 4 weeks. Animals in the treatment groups were orally administered simvastatin or CTS for 8 weeks. Oral glucose tolerance tests and insulin tolerance tests were performed. At the end of treatment, plasma lipid levels, and oxidative parameters in the liver were measured using commercial test kits. Western blotting was used to evaluate whether CTS induced AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase activation, and the expression of transcription factors and their target genes was evaluated in a quantitative PCR assay.ResultsCompared with the HFD group, the CTS (200 mg/kg/day) treatment group showed significantly decreased plasma lipid parameters (P < 0.001, P = 0.018, and P = 0.005 for triglycerides, total cholesterol and low-density lipoprotein cholesterol, respectively), and improved insulin resistance (P = 0.006). CTS (100 and 200 mg/kg/day) supplementation also reduced hepatic lipids and protected the liver from oxidative stress by attenuating malondialdehyde content (P < 0.001 and P < 0.001, respectively) and restoring aspartate aminotransferase levels (P < 0.001 and P < 0.001, respectively). Moreover, CTS (200 mg/kg/day) reduced lipid accumulation by enhancing AMPK phosphorylation and inhibiting expression of sterol regulatory element-binding proteins (SREBPs) and their target genes SREBP-1c, SREBP-2, fatty acid synthase, and stearoyl-CoA desaturase (P = 0.013, P = 0.007, P = 0.011, and P = 0.014, respectively).ConclusionCTS from I. latifolia improved insulin resistance and liver injury in HFD-fed mice, and attenuated NAFLD via the activation of AMPK and inhibition of the gene expression of SREBPs and some of their target molecules.

Energetics of endurance exercise in young horses determined by nuclear magnetic resonance metabolomics.

Long-term endurance exercise severely affects metabolism in both human and animal athletes resulting in serious risk of metabolic disorders during or after competition. Young horses (up to 6 years old) can compete in races up to 90 km despite limited scientific knowledge of energetic metabolism responses to long distance exercise in these animals. The hypothesis of this study was that there would be a strong effect of endurance exercise on the metabolomic profiles of young horses and that the energetic metabolism response in young horses would be different from that of more experienced horses. Metabolomic profiling is a powerful method that combines Nuclear Magnetic Resonance (NMR) spectrometry with supervised Orthogonal Projection on Latent Structure (OPLS) statistical analysis. 1H-NMR spectra were obtained from plasma samples drawn from young horses (before and after competition). The spectra obtained before and after the race from the same horse (92 samples) were compared using OPLS. The statistical parameters showed the robustness of the model (R2Y = 0.947, Q2Y = 0.856 and cros-validated ANOVA p < 0.001). For confirmation of the predictive value of the model, a test set of 104 sample spectra were projected by the model, which provided perfect predictions as the area under the receiving-operator curve was 1. The metabolomic profile determined with the OPLS model showed that glycemia after the race was lower than glycemia before the race, despite the involvement of lipid and protein catabolism. An OPLS model was calculated to compare spectra obtained on plasma taken after the race from 6-year-old horses and from experienced horses (cross-validated ANOVA p < 0.001). The comparison of metabolomic profiles in young horses to those from experienced horses showed that experienced horses maintained their glycemia with higher levels of lactate and a decrease of plasma lipids after the race.

The frog skin host-defense peptide CPF-SE1 improves glucose tolerance, insulin sensitivity and islet function and decreases plasma lipids in high-fat fed mice

The frog skin host-defense peptide CPF-SE1 has previously been shown to stimulate the in vitro release of insulin from clonal BRIN-BD11 β-cells. In this study, the in vivo effects of the peptide were investigated in male NIH Swiss mice maintained on a high-fat diet to induce obesity and insulin resistance. Insulin-secretory responses of islets isolated from treated and untreated mice and changes in islet morphology were also examined. Total body fat, plasma glucagon, triglyceride and cholesterol concentrations were measured at the end of the treatment period. Acute intraperitoneal administration of CPF-SE1 (75nmol body weight) to high-fat fed mice together with glucose (18mmol/kg body weight) improved glucose tolerance and insulin responses compared to high-fat fed controls. Long term administration of CPF-SE1 (twice-daily administration of 75nmol/kg body weight for 28 days) did not affect body weight or energy intake but decreased circulating glucose and increased insulin concentrations. Insulin sensitivity and insulin-secretory responses of islets to secretagogues were also significantly improved at 28 days in peptide-treated mice. In addition, significant decreases in plasma glucagon concentrations, pancreatic insulin and glucagon content, islet and beta cell area, body fat and plasma triglyceride levels were observed in CPF-SE1 treated with mice. In conclusion, CPF-SE1 improves beta cell function, insulin sensitivity and glycaemic control whilst reducing total body fat and circulating triglyceride levels. The peptide shows potential for development into an agent for treatment of patients with metabolic syndrome and type 2 diabetes.

Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression [S

Mammalian tribbles homolog 1 (TRIB1) is a human locus that has been shown to significantly impact plasma lipid levels across several ethnic groups. In addition, the gene has been associated with the occurrence of nonalcoholic fatty liver disease. In the present study, a yeast-two-hybrid system was used to screen for novel molecular targets of TRIB1 binding. Loci corresponding to clones that were positive for TRIB1 binding subsequently were assessed for roles in lipid metabolism in mice using adenoviral constructs to induce knockdown or overexpression. Sin3A-associated protein, 18 kDa (SAP18) was identified as a novel binding partner of TRIB1. Knockdown of the Sap18 in mouse liver decreased plasma lipid levels and increased hepatic lipid levels; SAP18 overexpression showed the opposite effects. Transcriptome analysis of the mouse liver revealed that Sap18 knockdown decreased and SAP18 overexpression increased microsomal TG transfer protein (MTTP) expression levels. Chromatin immunoprecipitation analysis showed that halo-tagged SAP18, halo-tagged TRIB1, and anti-mSin3A antibody enriched precipitates for regulatory sequences of the MTTP gene. Enforced expression of SAP18 enhanced and SAP18 knockdown conversely attenuated the enrichment of MTTP regulatory sequences seen with anti-mSin3A antibody. These studies indicated that SAP18 expression enhanced the recruitment of mSin3A in coordination with TRIB1 to MTTP regulatory elements and increased MTTP expression.

Resolution of statin-induced myalgia by correcting vitamin D deficiency: a case report

The onset of myalgia is a well-known side effect of cholesterol-lowering statins. Recent studiesa dvanced the hypothesis that reduced vitamin D levels may play a role in the onset of myalgia in statin users and potentially a vitamin D supplementation may be useful in these cases, as suggested by the present case report.A 52-year-old man with a history of smoke and successfully controlled hypertension presented with chest pain and asthenia. He was diagnosed with stable angina pectoris and discharged on atorvastatin. Due to the onset of myalgia, the dosage of atorvastatin was reduced (from 40 mg daily to 20 mg daily) and then atorvastatin was switched to rosuvastatin without symptoms improvement. Switching from rosuvastatin to ezetimibe resulted in pain improvement, but also in plasma lipids increase beyond the normal range. Ezetimibe was switched to rosuvastatin+ analgesic; in the meanwhile a high-performance liquid chromatography (HPLC) analysis showed low levels of 25-hydroxy-vitamin D and 1-25-dihydroxy-vitamin D. Therefore, vitamin D3 was added to rosuvastatin, resulting in pain improvement, decrease of plasma lipids and progressive discontinuation of analgesics. During the follow-up, rosuvastatin was switched to atorvastatin + vitamin D3, with a good control of plasma lipid levels and without the onset of myalgia.

NPC1L1 knockout protects against colitis-associated tumorigenesis in mice.

BackgroundColorectal cancer is strongly associated with lipid metabolism. NPC1L1, a sterol transporter, plays a key role in modulating lipid homeostasis in vivo. Its inhibitor, ezetimibe, began to be used clinically to lower cholesterol and this caused the great debate on its role in causing carcinogenesis. Here we explored the role of NPC1L1 in colorectal tumorigenesis.MethodsWild-type mice and NPC1L1−/− (NPC1L1 knockout) mice were treated with azoxymethane (AOM)-dextran sodium sulfate (DSS) to induce colitis-associated colorectal tumorigenesis. Mice were sacrificed 10, 15, 18 or 20 weeks after AOM treatment, respectively. Colorectal tumors were counted and analyzed. Plasma lipid concentrations were measured using enzymatic reagent kit. Protein expression level was assayed by western blot.ResultsNPC1L1−/− mice significantly had fewer tumors than wild-type. The ratio of malignant/tumor in NPC1L1−/− mice was significantly lower than in wild-type 20 weeks after AOM-DSS treatment. NPC1L1 was highly expressed in the small intestine of wild-type mice but its expression was undetectable in colorectal mucous membranes or tumors in either group. NPC1L1 knockout decreased plasma total cholesterol and phospholipid. NPC1L1−/− mice had significant lower intestinal inflammation scores and expressed inflammatory markers p-c-Jun, p-ERK and Caspase-1 p20 lower than wild-type. NPC1L1 knockout also reduced lymphadenectasis what may be caused by inflammation. NPC1L1 knockout in mice decreased β-catenin in tumors and regulated TGF-β and p-gp in adjacent colons or tumors. There was not detectable change of p53 by NPC1L1 knockout.ConclusionsOur results provide the first evidence that NPC1L1 knockout protects against colitis-associated tumorigenesis. NPC1L1 knockout decreasing plasma lipid, especially cholesterol, to reduce inflammation and decreasing β-catenin, p-c-Jun and p-ERK may be involved in the mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1230-0) contains supplementary material, which is available to authorized users.