The effects of exercise training programs on plasma concentrations of proenkephalin Peptide F and catecholamines

To determine if exercise training alters the pattern and magnitude of plasma concentrations of proenkephalin Peptide F and epinephrine, plasma proenkephalin [107–140] Peptide F_ir and catecholamines were examined pre-training (T-1), and after 4- (T-2), 8- (T-3), and 12-weeks (T-4) of training. 26 healthy men were matched and randomly assigned to one of three groups: heavy resistance strength training (Strength, n = 9), high intensity endurance training (Endurance, n = 8), or both training modalities combined (Combined, n = 9). Blood was collected using a syringe with a cannula inserted into a superficial arm vein with samples collected at rest, after each 7 min stage and 5 and 15 min into recovery. With training, all groups observed shifted plasma Peptide F responses to graded exercise, where significant increases were observed at lower exercise intensities. Increases in plasma epinephrine with exercise were observed in all groups. The Combined group saw increases at 25% at T-3 and for 50% at T-2, T-3, and T-4 which was higher than T-1. The Endurance group demonstrated increases for 50% at T-1, T-2, T-3 but not at T-4. The plasma epinephrine response to graded exercise was reduced in the Strength group. Increases in plasma norepinephrine above rest were observed starting at 50%

. The Strength group demonstrated a significant reduction in norepinephrine observed at 100% at T-3 and T-4. Peptide F and catecholamines responses to graded exercise can be altered by different types of physical exercise training. Simultaneous high intensity training may produce adrenal medulla exhaustion when compared to single mode training.     

ACTN3 Gene R577X Polymorphism Associated with High-Density Lipoprotein Cholesterol and Adiponectin in Rugby Players

Objective: To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes.Methods: Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype.Results: The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P<.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 μg/mL; P<.01), even after adjustments for confounders (P<.01).Conclusion: There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise.Abbreviations:ACTN3 = α-actinin-3BMI = body mass indexCVD = cardiovascular diseaseHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolR = arginine (R) at amino acid position 577 of the ACTN3 proteinTC = total cholesterolTG = triglycerideX = truncation at amino acid position 577 of the ACTN3 protein     

Lysophosphatidylcholine export by human ABCA7

The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1. Like ABCA1, ABCA7 exported choline phospholipids in the presence of apoA-I and apoE; however, unlike ABCA1, cholesterol efflux was marginal. Lipid efflux by ABCA7 was saturated by 5 μg/ml apoA-I and was not dependent on apoE isoforms, whereas efflux by ABCA1 was dependent on apoA-I up to 20 μg/ml and apoE isoforms. Liquid chromatography–tandem mass spectrometry analyses revealed that the two proteins had different preferences for phospholipid export: ABCA7 preferred phosphatidylcholine (PC) ≥ lysoPC > sphingomyelin (SM) = phosphatidylethanolamine (PE), whereas ABCA1 preferred PC > > SM > PE = lysoPC. The major difference in the pattern of lipid peaks between ABCA7 and ABCA1 was the high lysoPC/PC ratio of ABCA7. These results suggest that lysoPC is one of the major transport substrates for ABCA7 and that lysoPC export may be a physiologically important function of ABCA7 in the brain.     

High intensity interval exercise decreases IL-8 and enhances the immunomodulatory cytokine interleukin-10 in lean and overweight–obese individuals

PurposeTo compare the effects of two interval exercises with different intensities on acute inflammatory response in lean and overweight–obese subjects.MethodsTen lean (BMI < 24.9 kg/m²) and 12 overweight–obese (BMI 25 to <34.9 kg/m²) males performed two conditions in randomly assigned: (1) high intensity interval exercise (HIIE) 10 × 60 s (85–90%P_Max)/75 s (50%P_Max); (2) moderate intensity interval exercise (MIIE) 10 × 60 s (70–75%P_Max)/60 s (50%P_Max), with blood collections at pre, immediately and 30 min post each exercise bouts to evaluate total and differential leukocyte counts, serum creatine kinase (CK), lactate dehydrogenase (LDH) and systemic levels of IL-1ra, IL-6, IL-8, IL-10, IL-17a and CCL2.ResultsIn lean group, HIIE induced a significant increase in total leukocytes and monocyte, while MIIE session did not change the number of leukocytes. Overweight–obese group presented similar increase in leukocytes, monocytes and lymphocytes in both HIIE and MIIE sessions. At baseline, overweight–obese group showed high levels of CK, IL-8, IL-6 and CCL2 and lower concentrations of IL-10 compared to lean group. The MIIE did not alter the cytokine concentrations in both groups, independently of the time analysis. The HIIE induced significant decrease in IL-8 levels 30 min post session in both the groups, and a progressive elevation in IL-10 levels immediately and 30 min post in lean and overweight–obese. Regarding IL-6, overweight–obese subjects presented progressive increase either immediately and 30 min after HIIE, while lean individuals presented significant increase only 30 min after exercise.ConclusionsThe acute inflammatory response to interval exercise is intensity-dependent. Although obesity influences the basal concentrations of several cytokines, only HIIE induced important alterations in IL-8 and IL-10 levels, which may have important implications in the control of chronic low-grade inflammation in obesity.     

Regulation of plasma membrane Ca2 +-ATPase activity by acetylated tubulin: Influence of the lipid environment

We demonstrated previously that acetylated tubulin inhibits plasma membrane Ca^2 +-ATPase (PMCA) activity in plasma membrane vesicles (PMVs) of rat brain through a reversible interaction. Dissociation of the PMCA/tubulin complex leads to restoration of ATPase activity. We now report that, when the enzyme is reconstituted in phosphatidylcholine vesicles containing acidic or neutral lipids, tubulin not only loses its inhibitory effect but is also capable of activating PMCA. This alteration of the PMCA-inhibitory effect of tubulin was dependent on concentrations of both lipids and tubulin. Tubulin (300 μg/ml) in combination with acidic lipids at concentrations > 10%, increased PMCA activity up to 27-fold. The neutral lipid diacylglycerol (DAG), in combination with 50 μg/ml tubulin, increased PMCA activity > 12-fold, whereas tubulin alone at high concentration (≥ 300 μg/ml) produced only 80% increase. When DAG was generated in situ by phospholipase C incubation of PMVs pre-treated with exogenous tubulin, the inhibitory effect of tubulin on PMCA activity (ATP hydrolysis, and Ca^2 + transport within vesicles) was reversed. These findings indicate that PMCA is activated independently of surrounding lipid composition at low tubulin concentrations (< 50 μg/ml), whereas PMCA is activated mainly by reconstitution in acidic lipids at high tubulin concentrations. Regulation of PMCA activity by tubulin is thus dependent on both membrane lipid composition and tubulin concentration.     

Fucoxanthin supplementation improves plasma and hepatic lipid metabolism and blood glucose concentration in high-fat fed C57BL/6N mice

This study investigated the effects of fucoxanthin isolated from marine plant extracts on lipid metabolism and blood glucose concentration in high-fat diet fed C57BL/6N mice. The mice were divided into high-fat control (HFC; 20% fat, w/w), low-fucoxanthin (low-Fxn; HFC + 0.05% Fxn, w/w) and high-fucoxanthin (high-Fxn; HFC + 0.2% Fxn, w/w) groups. Fxn supplementation significantly lowered the concentration of plasma triglyceride with a concomitant increase of fecal lipids in comparison to the HFC group. Also, the hepatic lipid contents were significantly lowered in the Fxn supplemented groups which seemed to be due to the reduced activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase and phosphatidate phosphohydrolase and the enhanced activity of β-oxidation. Plasma high-density lipoprotein cholesterol concentrations and its percentage were markedly elevated by Fxn supplementation. Activities of two key cholesterol regulating enzymes: 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase, were significantly suppressed by Fxn regardless of the dosage. Relative mRNA expressions of acyl-coA oxidase 1, palmitoyl (ACOX1) and peroxisome proliferators activated receptor α (PPARα) and γ (PPARγ) were significantly altered by Fxn supplementation in the liver. Fxn also lowered blood glucose and HbA_1c levels along with plasma resistin and insulin concentrations. These results suggest that Fxn supplementation plays a beneficial role in not only regulating the plasma and hepatic lipids metabolism but also for blood glucose-lowering action in high-fat fed mice.     

Treadmill exercise enhances ABCA1 expression in rat liver

ATP-binding cassette transporters (ABCs) belong to a large family and include 49 mammalian transmembrane transporters that transfer a variety of substrates across the lipid bilayers in an energy-dependent manner. ABCA1 is a member of this family which plays a crucial role in plasma HDL-C remodeling. The purpose of this study was to investigate liver ABCA1 expression and plasma HDL level in response to treadmill running program in rats. Ten adult Wistar male rats (12-14weeks old, 200-220g) were used for this study. Animals were divided into control (Con, n=5) and Training (TR, n=5) groups. Training group was given exercise on a motor-driven treadmill at 25m/min (0% grade) for 90min/day, 5 days/week for 6 weeks. Rats were sacrificed 24h after the last session of exercise portion of the liver was excised, immediately washed in ice-cold saline, and frozen in liquid nitrogen for extraction of ABCA1 mRNA. Plasma was collected for HDL-C, LDL, TC, TG, and VLDL-C measurements. Liver ABCA1 mRNA expression was significantly (P<0.001) higher in trained rats compared to control rats. Plasma HDL-C, LCAT, pre-beta-HDL concentrations were significantly higher (P<0.01, P<0.001, P<0.028, respectively) in trained rats at the end of treadmill exercise. However, plasma lipids, other lipoproteins and TC/HDL and LDL/HDL ratio were unchanged. In conclusion, a treadmill running-induced elevated plasma HDL-C concentration was accompanied with a higher liver ABCA1 mRNA expression and increased in LCAT and pre-beta-HDL levels.     

Basal very low-density lipoprotein metabolism in response to exercise: Mechanisms of hypotriacylglycerolemia

Although the hypotriacylglycerolemic effect of exercise was described more than 40 years ago, the mechanisms responsible for triacylglycerol (TAG)-lowering have just recently started to be elucidated. Delayed-onset hypotriacylglycerolemia in the basal state, 1 day after a single bout of endurance exercise is due to augmented efficiency of very low-density lipoprotein (VLDL)-TAG removal from the circulation, likely mediated by the secretion of fewer but TAG-richer VLDL particles from the liver; exercise-induced changes in skeletal muscle lipoprotein lipase are more likely a contributing rather than the primary factor of TAG-lowering. This illustrates, in vivo, how changes in VLDL-apolipoprotein B-100 metabolism in the liver can effect changes in VLDL-TAG metabolism in the periphery. The exercise-induced increase in basal VLDL-TAG clearance rate plateaus at ～40%, whereas the threshold of energy that needs to be expended during endurance exercise lies near or above 500–600 kcal. Resistance exercise is more potent than endurance exercise in this respect. Exercise-induced changes in basal hepatic VLDL-TAG secretion 12–24 h after exercise are not negligible but span around zero; available data indicates that reduced hepatic VLDL-TAG secretion rate may be responsible for the persistence of hypotriacylglycerolemia at later time points (?48 h) after exercise cessation, or following training. Our understanding of the mechanisms leading to TAG-lowering after exercise has advanced considerably in recent years, but much remains to be learned.     

Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome

Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9 ± 1.2 years, BMI: 34.2 ± 1.1 kg/m²) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60 min/day for 5 days/week at ∼85% HR_max). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40 mU/m²/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75 g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P < 0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P < 0.001) and decreased HOMA-IR by 15% (P < 0.05). Training decreased plasma DPP-4 by 10% (421.8 ± 30.1 vs. 378.3 ± 32.5 ng/ml; P < 0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r = −0.59; P < 0.04), HOMA-IR (r = 0.59; P < 0.04) and fat oxidation (r = −0.54; P < 0.05). Increased fat oxidation also correlated with lower 2-h glucose levels (r = −0.64; P < 0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome.     

Serum cytokines and muscle strength after anterior cruciate ligament surgery are not modulated by high-doses of vitamins E (α- and γ-tocopherol’s) and C

The purpose of this investigation was to identify if supplemental vitamin E (consisting of α- and γ-tocopherol’s) and C modulate serum cytokine and muscle strength following an ACL injury and surgery. Subjects were randomly assigned to one of two groups: (1) placebo (n = 14) or (2) vitamins E (α-[600 mg RRR-α-tocopherol, αT] and γ-[600 mg of RRR-γT]) and C (1000 mg ascorbic acid, AA) (EC; n = 15). Supplements were taken daily starting ∼2-wk prior to and concluding 16-wk after surgery. Fasting blood samples were obtained and single-leg peak isometric force measurements were performed at baseline (prior to supplementation), before surgery (∼120-min – blood draw only), and 8-wk, 12-wk, and 16-wk after surgery. αT, γT, AA, and cytokines were measured in each blood sample, and peak isometric force was measured on the injured and non-injured legs separately at each testing session. An exercise protocol consisting of repetitive knee and hip extension and flexion contractions to exhaustion was performed on the injured limb at 16-wk. Vitamin E and C supplementation significantly (all p < 0.05) increased plasma αT (∼40%), γT (∼160%), and AA (∼50%) concentrations. Serum cytokine concentrations, peak isometric force, and time to exhaustion during the exercise protocol were not significantly different between groups. Based on these findings, we conclude that vitamin E and C supplementation increases their endogenous levels without minimizing muscular weakness or modulating serum cytokine concentrations after ACL surgery.     

The beneficial effects of rosuvastatin are independent of zinc supplementation in patients with atherosclerosis

BackgroundStatins have multiple antiatherosclerotic effects, but can reduce blood plasma concentrations of minerals, including zinc. As zinc possesses antiinflammatory and antioxidant effects, low zinc status can promote injuries or inadequate tissue repair in endothelial cells. Metallothionein (MT) expression might modulate responses induced by statins in patients with atherosclerosis. However, research regarding mineral status and the use of statins is scarce. This study evaluated the effects of zinc supplementation on zinc status and expression of the zinc-dependent MT1F and MT2A genes in patients with atherosclerosis treated with rosuvastatin.MethodsA double-blind, randomized clinical trial was performed with 54 participants treated with 10 mg rosuvastatin for 4 months with or without zinc supplementation (30 mg/day). Diet, lipid profile, high-sensitivity reactive protein C (hs-CRP), plasma and erythrocyte zinc concentrations, erythrocyte superoxide dismutase (SOD) activity, and MT1F and MT2A genes expression were analyzed before and after intervention.ResultsRosuvastatin therapy was effective in reducing low- and non-high-density lipoprotein, total cholesterol, triglycerides, and hs-CRP levels, independent of zinc supplementation. Additionally, zinc treatment had no effect on SOD enzyme activity (P = 0.201), plasma (P > 0.671) and erythrocyte (P > 0.123) zinc concentrations, or the pattern of MT1F and MT2A genes expression (P = 0.088 and P = 0.229, respectively).ConclusionsThe effectiveness of rosuvastatin treatment is independent of the effects of zinc supplementation. Moreover, rosuvastatin treatment did not have a significant impact on zinc status or MT1F and MT2A genes expression in patients with atherosclerosis.     

Structure-function relationships in reconstituted HDL: Focus on antioxidative activity and cholesterol efflux capacity

AimsHigh-density lipoprotein (HDL) contains multiple components that endow it with biological activities. Apolipoprotein A-I (apoA-I) and surface phospholipids contribute to these activities; however, structure-function relationships in HDL particles remain incompletely characterised.MethodsReconstituted HDLs (rHDLs) were prepared from apoA-I and soy phosphatidylcholine (PC) at molar ratios of 1:50, 1:100 and 1:150. Oxidative status of apoA-I was varied using controlled oxidation of Met112 residue. HDL-mediated inactivation of PC hydroperoxides (PCOOH) derived from mildly pre-oxidized low-density lipoprotein (LDL) was evaluated by HPLC with chemiluminescent detection in HDL + LDL mixtures and re-isolated LDL. Cellular cholesterol efflux was characterised in RAW264.7 macrophages.ResultsrHDL inactivated LDL-derived PCOOH in a dose- and time-dependent manner. The capacity of rHDL to both inactivate PCOOH and efflux cholesterol via ATP-binding cassette transporter A1 (ABCA1) increased with increasing apoA-I/PC ratio proportionally to the apoA-I content in rHDL. Controlled oxidation of apoA-I Met112 gradually decreased PCOOH-inactivating capacity of rHDL but increased ABCA1-mediated cellular cholesterol efflux.ConclusionsIncreasing apoA-I content in rHDL enhanced its antioxidative activity towards oxidized LDL and cholesterol efflux capacity via ABCA1, whereas oxidation of apoA-I Met112 decreased the antioxidative activity but increased the cholesterol efflux. These findings provide important considerations in the design of future HDL therapeutics.Non-standard abbreviations and acronyms: AAPH, 2,2′-azobis(-amidinopropane) dihydrochloride; ABCA1, ATP-binding cassette transporter A1; apoA-I, apolipoprotein A-I; BHT, butylated hydroxytoluene; CV, cardiovascular; EDTA, ethylenediaminetetraacetic acid; HDL-C, high-density lipoprotein cholesterol; LOOH, lipid hydroperoxides; Met(O), methionine sulfoxide; Met112, methionine 112 residue; Met86, methionine 86 residue; oxLDL, oxidized low-density lipoprotein; PBS, phosphate-buffered saline; PC, phosphatidylcholine; PL, phospholipid; PCOOH, phosphatidylcholine hydroperoxide; PLOOH, phospholipid hydroperoxide.     

Apolipoprotein A-I inhibits chemotaxis,adhesion, activation of THP-1 cells and improves the plasma HDL inflammatory index

The anti-inflammatory effects of high density lipoprotein (HDL) are well described, however, such effects of Apolipoprotein A-I (ApoA-I) are less studied. Building on our previous study, we further explored the mechanism of anti-inflammatory effects of ApoA-I, and focused especially on the interaction between monocyte and endothelial cells and plasma HDL inflammatory index in LPS-challenged rabbits. Our results show that ApoA-I significantly decreased LPS-induced MCP-1 release from THP-1 cells and ox-LDL-induced THP-1 migration ratio (P < 0.01, respectively). ApoA-I significantly decreased sL-selectin, sICAM-1 and sVCAM-1 release (P < 0.01, P < 0.01, P < 0.05, respectively) from LPS-stimulated THP-1 cells. Furthermore, ApoA-I significantly inhibited LPS-induced CD11b and VCAM-1 expression on THP-1 cells (P < 0.01, P < 0.05, respectively). ApoA-I diminished LPS-induced mCD14 expression (P < 0.01) and NFκB nuclear translocation in THP-1 cells. After single dose treatment of ApoA-I, the value of plasma HDL inflammatory index in LPS-challenged rabbits was improved significantly (P < 0.05). These results suggest that ApoA-I can inhibit chemotaxis, adhesion and activation of human monocytes and improve plasma HDL inflammatory index with presenting beneficial anti-inflammatory effects.     

Regulation of lipid metabolism in the snow alga Chlamydomonas nivalis in response to NaCl stress: An integrated analysis by cytomic and lipidomic approaches

The cultures of the snow alga Chlamydomonas nivalis in the exponential phage were stressed by NaCl (up to 1.5%) for 0～48 h, followed by Nile Red staining-based cytomic analysis (flow cytometry and confocal laser scanning microscopy). The fluorescent intensities of total lipids, and neutral and polar lipids increased to the maximum within 7 h in the NaCl stressed cells with the highest increase in total lipids by 2-fold (0.75%-NaCl for 7 h), the highest increase in neutral lipids by 68-fold (1%-NaCl for 7 h) and the highest increase in polar lipids by 10-fold (1.25%-NaCl for 5 h), respectively. Seven types and 22 kinds of polar lipid molecules were selected and identified as biomarkers by UPLC/Q-TOF-MS-based lipidomic analysis, which demonstrated differences in total lipids between the stress group (0.75%-NaCl for 7 h) and the control. The biological roles of the biomarkers in the alga under NaCl stress were discussed. The integrated approach based on “omics” technologies developed in the present work is validated as a powerful tool to successfully reveal the regulation of lipid metabolism in microalgae in response to stress stimulation.     

Colesevelam Hydrochloride Added to Background Metformin Therapy in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from 3 Clinical Studies

ObjectiveTo evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).MethodsThis post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo- controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.ResultsIn this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A_1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P < .001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P < .0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: + 12.8%; P < .0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: + 3.3%; P < .0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.ConclusionWhen added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non- HDL-C, and apo B in patients with inadequately controlled T2DM. (Endocr Pract. 2011;17:933-938)     

High levels of plasma selenium are associated with metabolic syndrome and elevated fasting plasma glucose in a Chinese population: A case-control study

BackgroundSelenium is important for human health and involved in various metabolic processes. Deficiency of selenium associates with increased risk for cancer and cardiovascular diseases. There has been an increase use of selenium supplements for the treatment of autoimmune thyroid conditions. However, the potential biological effects of selenium overload arouse the public concern. The aim of this study was to investigate the associations of plasma selenium concentrations of adults with metabolic syndrome (MS) in Chinese population.MethodsA matched case-control study including 204 metabolic syndrome patients and 204 healthy controls was conducted in 2012. The MS cases were defined according to the criteria of Chinese Diabetes Society (CDS). Healthy controls without abnormality of metabolic components were matched with cases in age, gender and region. Plasma concentrations of selenium were determined by graphite furnace atomic absorption spectrometry (GFAAS). Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were detected by automatic biochemical analyzer.ResultsThe median levels of plasma selenium in MS group were 146.3 (107.3–199.4) μg/L, which were significantly higher than that in the control group (127.4: 95.7–176.0) μg/L; Plasma levels of selenium were related to the risk of MS in dose-response manner. Risk of MS was significantly higher in subjects with plasma selenium in the highest tertile (T3: ≥176.0 μg/L) compared to those in the lowest tertile (T1: <95.7 μg/L) [odds ratio (OR) = 2.416 (95% CI: 1.289–4.526)]. The plasma levels of selenium were positively correlated with fasting plasma glucose (FPG) (r_s = 0.268, P < 0.001). Plasma selenium at the median (T2: 95.7–176.0 μg/L) or upper tertile (T3: ≥176.0 μg/L) was associated with increased risk of elevated FPG (defined by FPG ≥ 6.1 mmol/L) as compared with the lowest tertile (T1: ≤95.7 μg/L) [T2 vs. T1, OR = 3.487 (1.738–6.996); T3 vs. T1, OR = 6.245 (3.005–12.981)].ConclusionsHigher levels of plasma selenium might increase the risk of metabolic syndrome and elevated fasting plasma glucose. Selenium supplements should be used with prudence for CVD and cancer prevention.     

Antihyperlipidemic effect of chlorogenic acid and tetrahydrocurcumin in rats subjected to diabetogenic agents

Diabetes mellitus is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. The present study was carried out to evaluate the effects of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) alone and in combination on alterations in lipids, lipoproteins and enzymes involved in lipid metabolism in streptozotocin (STZ)–nicotinamide (NA)-induced type 2 diabetic rats. A significant (p < 0.05) increase in the concentrations of plasma and tissue (liver and kidney) lipids (cholesterol, triglycerides (TGs), free fatty acids (FFAs) and phospholipids (PLs)) and low density and very low-density lipoproteins (LDL and VLDL), and a decrease in the concentration of high-density lipoproteins (HDL) were noticed in STZ administered diabetic rats. In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly (p < 0.05) in the liver and kidney whereas the activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly (p < 0.05) in the plasma of diabetic rats. Combined administration of CGA (5 mg/kg b.w.) and THC (80 mg/kg b.w.) for 45 days remarkably reduced the STZ-induced changes in lipids, lipoproteins and lipid metabolising enzymes when compared to the effects of CGA or THC alone in diabetic rats. These results indicate that combination of THC and CGA can potentially ameliorate lipid abnormalities in experimental type 2 diabetes.     

Biarylether amide quinolines as liver X receptor agonists

A series of 4-(amido-biarylether)-quinolines was prepared as potential LXR agonists. Appropriate substitution with amide groups provided high affinity LXR ligands, some with excellent potency and efficacy in functional assays of LXR activity. Novel amide 4g had a binding IC₅₀ = 1.9 nM for LXRβ and EC₅₀ = 34 nM (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide substitution are potent LXR agonists     

Hybrid cooling vest for cooling between exercise bouts in the heat: Effects and practical considerations

While continuous cooling strategies may induce some ergonomic problems to occupational workers, cooling between work bouts may be an alternative for cooling them down in hot environments. The purpose of this study was to assess the effects of wearing a newly designed hybrid cooling vest (HCV) between two bouts of exercise. Inside a climatic chamber set at an air temperature of 37 °C and a relative humidity of 60%, twelve male participants underwent two bouts of intermittent exercise interspersed with a 30 min between-bout recovery session, during which HCV or a passive rest without any cooling (PAS) was administered. The results indicated that thermoregulatory, physiological, and perceptual strains were significantly lower in HCV than those in PAS during the recovery session (p≤0.022), which were accompanied with a large effect of cooling (Cohen's d=0.84–2.11). For the second exercise bout, the exercise time following HCV (22.13±12.27 min) was significantly longer than that following PAS (11.04±3.40 min, p=0.005, d=1.23) During this period, core temperature T_c was significantly lower by 0.14±0.0.15 °C in HCV than that in PAS. The heart rate drift over time was declined by 2±2 bpm min⁻¹ (p=0.001, d=1.00) and the rise in physiological strain index was reduced by 0.11±0.12 unit min⁻¹ (p=0.010, d=0.96) following the use of HCV. These findings suggested that using HCV could accelerate between-bout recovery and improve subsequent exercise performance by the enlarged body core temperature margin and blunted cardiovascular drift.