Plasma Cholesterol Concentrations Research Articles

Effects of Voluntary Wheel Running on Markers of NASH During Weight‐Loss in C57Bl/6 Mice

Non‐alcoholic steatohepatitis (NASH) is a liver condition characterized as excess lipid accumulation (>7%) and chronic low‐grade inflammation. The pathogenesis of NASH is generalized as multi‐factorial; however, recent evidence proposed a unifocal model in which an imbalance in cholesterol homeostasis is a dominant cause and other co‐factors modify the disease progression. The imbalance in cholesterol homeostasis leads to an accumulation of hepatic cholesterol triggering an inflammatory state subsequently sensitizing the liver to the development of hepatic fibrosis. Central to preventing hepatic fibrosis is bone morphogenic protein and activin membrane bound inhibitor (BAMBI), which inhibits the fibrogenic cascade by serving as pseudoreceptor for the pro‐fibrotic protein, transforming growth factor‐β1 (TGF‐β1). Weight‐loss is central to the management of NASH; however, the therapeutic benefits of exercise during weight‐loss remain unclear as it relates to treating NASH. Therefore, the purpose of this study was to determine if voluntary wheel running (VWR) during weight‐loss improves markers of hepatic steatosis and steatohepatitis versus diet alone in C57Bl/6 mice. Male C57Bl/6 mice were fed a 60% high‐fat diet (HF) for 10 wks to induce obesity. To produce weight loss, HF mice were randomly assigned to a normal diet (ND) either with (WL+VWR) or without (WL) access to running wheels for 8 wks. Age‐matched lean and obese mice were fed a ND and HF, respectively, for 18 wks. At 18 wks, the addition of VWR to weight‐loss resulted in a lower body mass (30.3±0.7 vs. 26.1±0.3 g, p<0.05) than by diet alone; however, HOMA‐IR was not different between WL and WL+VWR, but was 80.5–85.3% (p<0.05) lower than HF. In comparison to HF, WL and WL+VWR had significantly (p<0.05) lower plasma cholesterol (39.8%‐48.1%) and interleukin‐1β (IL‐1β; 46.3–71.6%) concentrations. As expected, WL and WL+VWR resulted in significantly (p<0.05) lower total hepatic lipid (78.8–81.4%) and triglyceride (62.1–77.1%) when compared to HF that was associated with reduced expression of peroxisome proliferator‐activated receptor‐γ (PPARγ; 56.1–71.7%) and CD36 (73.8–80.7%). Interestingly, WL+VWR resulted in significantly (p<0.05) lower hepatic triglyceride (9.6±1.5 vs. 5.8±0.7 mg/mg tissue) and cholesterol (5.3±0.6 vs. 3.2±0.3 mg/mg tissue) when compared to WL. Despite weight‐loss, the toll like receptor 4 (TLR4) mediated intracellular inflammatory signaling cascade remained elevated in both WL and WL+VWR, which was comparable to the HF group. However, WL+VWR had significantly (p<0.05) lower hepatic expression of IL‐1β (65.0–66.3%) and IL‐6 (44.0–58.0%) compared to ND and WL. The lower IL‐1β and IL‐6 hepatic expression may be due in part to a 1.3‐ to 3.8‐fold (p<0.05) greater expression of BAMBI in WL and WL+VWR. In summary, despite significant improvements in circulating and hepatic markers for glucose and lipid metabolism, a transient inflammatory state remained following weight‐loss by diet alone. In contrast, the exercise‐induced increase in hepatic BAMBI and reductions in IL‐1β and IL‐6 during weight‐loss suggests a protective effect of exercise.Support or Funding InformationThis study was supported by the Seed Grants for Translational and Exploratory Projects (J.S.W.) and the Undergraduate Creative Arts and Research Program (K.E.P. and A.S.) at Southern Illinois University Edwardsville.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

EFFICIENCY OF USING RICE HUSKS IN FEEDING GROWING RABBITS AS ANTI-AFLATOXINS

This experiment was carried out to investigate the effect of using rice husks (RH) like anti- aflatoxins and source of fibers at 0, 3, 6, 9 and 12 % as replaced clover hay in the rations of growing rabbits. Seventy-five unsexed, weaned New Zealand White rabbits of 5 weeks old were randomly divided into five experimental groups (15 rabbits / group). The trial continued for 8 weeks. The results obtained showed that using rice husks in growing rabbits diets: low content significant of total aflatoxins in growing rabbit diets and faeces. No significant effect on productive performance (live body weight, daily body weight gains and feed conversion ratio), expect 3% RH was highly significant in feed consumption compared with control group. The control group numerically highest but not significant (P>.05) for TDN value and digestibility coefficients of dry matter, organic matter, crude protein, crude fiber and nitrogen free extract compared to RH groups. Rabbits fed 12% RH had the lowest values (P>.05) for digestibility coefficients of organic matter, crude protein, crude fiber and nitrogen free extract compared to the other groups, however, it showed significantly (P<.05) higher digestibility of ether extract than other groups. Higher dressing and weight of hot carcass percentages were recorded for rabbits fed 3% RH. Plasma total protein, albumin, globulin, A/G ratio, total lipids, cholesterol or alanine aminotransferase (ALT) concentration were not significantly affected due to including RH into rabbit diets. However aspartate aminotransferase (AST) was significantly decreased by different levels of RH. Rabbits had 6% RH in their diet showed higher economic efficiency percentage compared with other group. The results revealed that 6% RH can be used in growing rabbit diets as anti–total aflatoxins and source of fiber without any adverse effect on productive performance and carcass characteristics with high obtained economic efficiency value.

Dyslipidemia.

Dyslipidemia.

Egg consumption and risk of cardiovascular diseases, evidence from China Health and Nutrition Survey 2000–2011

ObjectiveThe morbidity and hospitalization of CVDs in China have kept increasing since 2000, outpacing the GDP growth. CVD may bring heavier burden in the coming decade to Chinese people, economically and physically. There are evidence indicating the strong relationship between high plasma concentration of cholesterol and CVDs, but the association between CVDs and dietary cholesterol intake remains unclear. We therefore conducted a longitudinal analysis with multifactor adjusting models to assess the nonfatal myocardial infarction (MI) and stroke risks of egg consumption in a sample of Chinese adults.MethodFive rounds of China Health and Nutrition Survey from 2000 to 2011 were used in this study. 5289 non‐myocardial infarction or non‐stroke subjects &gt;30y in 2000 and followed at least once in the subsequence rounds were included in the final analysis. Three consecutive 24h dietary recall was used to collect egg consumption data, and self‐reported nonfatal MI and stroke history at each follow‐up was used for the CVD diagnosis. Cox proportional hazards regression models with time‐dependent explanatory variables was conducted to compute relative risks and 95% CIs.ResultThe follow‐up time of the myocardial infarction(MI) patients was averagely 9.62 years, while that of the stroke patients was 9.59 years. In 2000, the average daily egg consumption of the whole population was 50.01±38.39g/day, while the figure slightly decreased in the year of 2011, at 46.52 ±34.18g/day. Adjusted for age, gender, education level, household income, urbanized level, geographic location, and individual behavioral factors (including drinking, smoking, physical activity level, weight status, and chronic disease history ), multivariate Cox regression analysis revealed that egg consumption was not a significant risk factor of the CVDs in this study(MI and stroke).ConclusionOur study shows no significant relation between egg consumption and CVD risks in this population of which egg consumption was mostly below 100g/day.Support or Funding InformationThe authors thank the team at National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, and the Carolina Population Center, University of North Carolina at Chapel Hill. The China Health and Nutrition Survey data collection was in part funded by research grants from the NIH (R01‐HD30880, DK056350, R24 HD050924, and R01‐HD38700) and the NIH Fogarty International Center and by the Chinese Center for Disease Control and Prevention. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views of the funders.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of Doublesynch and Estradoublesynch protocols on estrus induction, conception rate, plasma progesterone, protein, and cholesterol profile in anestrus Gir heifers.

AimThis study aimed to evaluate the efficacy of Doublesynch and Estradoublesynch protocols on estrus induction, conception rates, plasma progesterone, protein, and cholesterol profile in anestrus Gir heifers.Materials and MethodsIn this study, 50 pubertal anestrus Gir heifers were selected from the field and farm conditions. The heifers were dewormed (injection ivermectin, 100 mg, s/c) and supplemented with minerals and vitamins (injection organic phosphorus 800 mg and injection Vitamin AD3E and Biotin 10 ml i/m) and multi-mineral bolus at 1 bolus daily for 7 days. The heifers were randomly divided into three groups: Doublesynch (n=20), Estradoublesynch (n=20), and control (n=10). The animals were monitored for estrus response, estrus interval, behavioral signs, and conception rates after induced/first, second, and third cycle post-treatment. Blood samples were obtained on day 0, day 9, day 12, and on day 12 post-artificial insemination (AI) for determination of plasma progesterone, protein, and cholesterol profile.ResultsThe estrus response rate between Doublesynch and Estradoublesynch protocols was similar between treated heifers (85% and 95%). The interval from the second prostaglandin F2α (PGF2α) injection to estrus induction did not differ between the groups (63.87±4.19 vs. 58.27±3.83 h). The conception rates following induced estrus (20% vs. 30%), at the second cycle (23.07% vs. 16.66%), at the third cycle (22.22% vs. 30.00%), and the overall conception rate (45% and 55%) within 27.89±5.75 and 26.45±5.48 days were the same across the treatment groups. The mean plasma progesterone concentrations were significantly (p<0.01) higher on day 9 (second PGF2α injection) and day 12 post-AI compared to day 0 (first PGF2α injection) and the day of fixed-timed artificial insemination. The concentrations were also significantly (p<0.05) higher in conceived than non-conceived heifers on day 9 of treatment and day 12 post-AI in both the protocols. The mean plasma cholesterol concentrations were significantly higher during peak follicular and luteal phases compared to the initial anestrus phase in both the protocols. The values were also higher in non-conceived than conceived animals in both the protocols. The plasma protein profile was not influenced by the sampling days or conceived and non-conceived status.ConclusionThe results showed that both Doublesynch and Estradoublesynch protocols resulted in similar estrus induction and conception rates with modulation of plasma progesterone and cholesterol profile in anestrus Gir heifers.

Supplementation with sunflower seeds in beef cattle did not impact on oocyte and in vitro embryo production.

Supplementation with compounds rich in linoleic acid, including sunflower seed supplementation, promotes increase in conception rates in cows. We aimed to evaluate whether the sunflower seed (linoleic acid source) supplementation in beef donor females alters the plasma concentrations of cholesterol, triglycerides, HDL and LDL, increases the number and quality of oocytes, increases the cleavage rates and determines an improvement in number and quality of in vitro produced blastocysts. Thus, Nelore females were divided into two groups of 15 animals to receive supplementation with or without sunflower seed for 57days. Females underwent follicular aspiration and the oocytes were subjected to in vitro embryo production. There was no difference (p>.1) between control group and group supplemented with sunflower seed on the number of displayed follicles; number of aspired oocytes; recovery rate; cleavage rate; number of embryos; number of blastocysts; embryos number of grades I and II; plasma concentrations of total cholesterol, triglycerides; HDL and LDL. Therefore, sunflower seed supplementation in oocyte donors did not increase the number and quality of oocytes, cleavage rates and the number and quality of blastocysts produced in vitro.

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient (Ldlr-/-) mice (8-12 weeks old) that were Par2+/+ or Par2-/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2- and Cxcl1-induced monocyte infiltration.

Growth and biochemical markers of preterm newborns up to six months of corrected age

Introduction: Due to advances in recent decades in maternal-foetal and neonatal medicine, a greater survival of preterm infants with progressively smaller birth weight and gestational age is observed, increasing the risk of future morbidities on those infants. Among these morbidities, alterations in growth and metabolism are found. Objective: To analyze the evolution of the growth and the metabolic profile of preterm infants’ cohort from birth at six months of corrected age (CA).Methods: A descriptive and prospective study with a sample of 107 mothers and 115 preterm infants at birth and 72 preterm infants and 68 mothers at the end of follow-up. Growth (body weight, height, cephalic perimeter) was evaluated at six time points. Plasma concentrations of cholesterol, triglycerides, glucose and insulin of premature infants were assessed during three periods, from birth to 6 months of CA. Comparative analysis of the initial sample and the sample that finished the follow-up was used in chi-square family tests. To Evaluate the growth over the 6-month period by using repeated measurements.Results: Sociodemographic variables and maternal biochemical profile without statistical differences in the comparison of the mothers of the initial sample with those who completed the follow-up. Linear growth of preterm infants at six months of CA, however without recovery of growth. Plasma concentrations of triglycerides (birth = 48.1, 6 months = 151.1) and cholesterol (birth = 82.7, 6 months = 139.9) increased during the evaluations. Glycaemia remained stable (birth 80.4, 6 months = 83.3) and insulin decreased from 11.0 to 4.2.Conclusion: Growth of preterm infants, although linear, was lower than expected for age. Lipid profiles presented an ascending curve from birth onward. Therefore, this group is prone to delayed growth and to developing cardiovascular changes throughout life.

Retrospective evaluation of plasma cholesterol concentration in septic dogs and its association with morbidity and mortality: 51 cases (2005–2015)

To determine whether plasma cholesterol concentrations in dogs with sepsis is associated with morbidity or in-hospital mortality. Retrospective cohort study from 2005-2015. Two private referral centers. Fifty-one dogs diagnosed with sepsis. None. Dogs were classified as septic if they displayed ≥2 criteria of the systemic inflammatory response syndrome in conjunction with a documented underlying infectious cause. Dogs were excluded if they had been diagnosed previously with any concurrent illness reported to alter plasma cholesterol concentrations. Plasma cholesterol concentrations at the time of sepsis diagnosis were statistically analyzed for association with morbidity, as measured by the presence of organ dysfunction, the number of dysfunctional organs, duration of hospitalization, cost of hospitalization, and in-hospital mortality. Twenty-eight (55%) dogs survived to discharge, 15 (29%) were euthanized during hospitalization, and 8 (16%) died despite treatment. While median cholesterol concentrations were significantly different when comparing survivors to discharge versus nonsurvivors who died naturally despite treatment (P = 0.0245), they were not significantly different when comparing survivors to all nonsurvivors (P = 0.1821). Receiver operating characteristic curve analysis showed a cholesterol cutoff of 4.5 mmol/L (174 mg/dL) with a sensitivity of 75% and a specificity of 50% for predicting in-hospital mortality. For surviving dogs, plasma cholesterol concentrations were not associated with increased length of hospital stay. Number of dysfunctional organs and plasma cholesterol concentration were the 2 most significant individual predictors for survival, and when incorporated into a multivariate logistic regression model used for prediction, the model yielded a sensitivity of 94% and specificity of 63%. Plasma cholesterol concentration can provide prognostic information in dogs with sepsis. Further prospective studies investigating the role of cholesterol in sepsis are needed.

Intake of 3 Eggs per Day When Compared to a Choline Bitartrate Supplement, Downregulates Cholesterol Synthesis without Changing the LDL/HDL Ratio.

Cardiovascular disease (CVD) risk is associated with high concentrations of low-density lipoprotein cholesterol (LDL-C). The impact of dietary cholesterol on plasma lipid concentrations still remains a concern. The effects of egg intake in comparison to choline bitartrate supplement was studied in a young, healthy population. Thirty participants were enrolled for a 13-week intervention. After a 2-week run-in period, subjects were randomized to consume either 3 eggs/day or a choline bitartrate supplement (~400 mg choline for both treatments) for 4-weeks each. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records, plasma lipids, apolipoproteins (apo) concentrations, and peripheral blood mononuclear cell expression of regulatory genes for cholesterol homeostasis were assessed at the end of each intervention. Dietary intakes of saturated and monounsaturated fat were higher with the consumption of eggs compared to the choline period. In addition, higher plasma concentrations of total cholesterol (7.5%), high density lipoprotein cholesterol (HDL-C) (5%) and LDL-C (8.1%) were observed with egg consumption (p < 0.01), while no change was seen in LDL-C/HDL-C ratio, a key marker of heart disease risk. Compared to choline supplementation, intake of eggs resulted in higher concentrations of plasma apoA-I (8%) and apoE (17%) with no changes in apoB. Sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase expression were lower with egg consumption by 18% and 31%, respectively (p < 0.05), suggesting a compensation to the increased dietary cholesterol load. Therefore, dietary cholesterol from eggs appears to regulate endogenous synthesis of cholesterol in such a way that the LDL-C/HDL-C ratio is maintained.

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans.

Hypolipidemic and Antidiabetic Effects of Functional Rice Cookies in High-Fat Diet-Fed ICR Mice and db/db Mice.

We have previously reported the lipid-lowering effects of a Korean rice cookie called dasik (RCD) in comparison with a western style cookie. In this study, Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) fruit-supplemented RCD (SRCD) was added to a diet, and the hypolipidemic and antidiabetic effects of different diets were examined by using the ICR and db/db mouse models, respectively. ICR mice were fed the AIN-76 diet, or high-fat diet (HFD), or the RCD- or SRCD-supplemented HFD (10%, w/w) for 9 weeks (n = 7 per group). Compared with the RCD group, plasma and hepatic triglyceride and cholesterol concentrations were decreased in the SRCD group. Hepatic expressions for fatty acid and cholesterol synthesis were downregulated, whereas those for beta-oxidation and cholesterol export were upregulated (P < .05). The antidiabetic effects of SRCD were tested in db/db mice for 10 weeks (n = 7 per group). Glucose tolerance was improved in the SRCD group through the regulation of gluconeogenic enzymes and biomarkers related to the insulin signaling pathway (P < .05). In addition, SRCD increased the expression levels of antioxidative enzymes, and decreased those of inflammatory cytokines (P < .05). Moreover, oxidative stress, leptin, and insulin levels were lower in the SRCD group than in the other groups (P < .05). In conclusion, the lipid-lowering and antidiabetic effects of SRCD were greater than those of RCD with respect to the suppression of lipid synthesis, oxidative stress, and inflammation and the improvement of glucose metabolism.

Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia

Oxysterols (OHC) are biologically active cholesterol metabolites circulating in plasma that may be formed enzymatically (e.g. 24S-OHC, 25-OHC and 27-OHC) or by autoxidative mechanisms (e.g. 7-ketocholesterol, 7β-OHC and 25-OHC). Oxysterols are more soluble than cholesterol and are reported to exert inflammatory, cytoprotective and apoptotic effects according to concentration and species. Esterified oxysterols have been analysed in people with dementia and cardiovascular diseases although there is no consistent relationship between oxysterol esters and disease. However, oxysterol esters are held in lipoprotein core and may not relate to the concentration and activity of plasma free oxysterols. Methodological limitations have challenged the analysis of free oxysterols to date.We have developed a fast, sensitive and specific quantitative LC-MS/MS, multiple reaction monitoring (MRM) method to target five oxysterols in human plasma with analyte recoveries between 72% and 82% and sensitivities between 5 and 135 pg/ml. A novel method was used to investigate the hypothesis that simvastatin may reduce the concentrations of specific plasma free oxysterols in hypercholesterolaemia.Twenty healthy male volunteers were recruited (aged 41–63 years); ten were asymptomatic with high plasma cholesterol > 6.5 mM and ten were healthy with normal plasma cholesterol (< 6.5 mM). Simvastatin (40 mg/day) was prescribed to those with hypercholesterolaemia. Plasma samples were taken from both groups at baseline and after three months. Simvastatin reduced plasma cholesterol by ~35% (p < 0.05) at the end of three months.Oxysterols generated by autoxidation (but not enzymatically) were elevated up to 45 fold in hypercholesterolaemic midlife men. Plasma oxysterols were restored to those of healthy controls after simvastatin intervention suggesting that autoxidation is either prevented by simvastatin directly or that autoxidation is less prevalent when plasma cholesterol concentrations are within the normal range.

Fractal analysis of plaque border, a novel method for the quantification of atherosclerotic plaque contour irregularity, is associated with pro-atherogenic plasma lipid profile in subjects with non-obstructive carotid stenoses.

Background and aimsPlaque border irregularity is a known imaging characteristic of vulnerable plaques, but its evaluation heavily relies on subjective evaluation and operator expertise. Aim of the present work is to propose a novel fractal-analysis based method for the quantification of atherosclerotic plaque border irregularity and assess its relation with cardiovascular risk factors.Methods and resultsForty-two asymptomatic subjects with carotid stenosis underwent ultrasound evaluation and assessment of cardiovascular risk factors. Total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) plasma cholesterol and triglycerides concentrations were measured for each subject. Fractal analysis was performed in all the carotid segments affected by atherosclerosis, i.e. 147 segments. The resulting fractal dimension (FD) is a measure of irregularity of plaque profile on long axis view of the plaque. FD in the severest stenosis (main plaque FD,mFD) was 1.136±0.039. Average FD per patient (global FD,gFD) was 1.145±0.039. FD was independent of other plaque characteristics. mFD significantly correlated with plasma HDL (r = -0.367,p = 0.02) and triglycerides-to-HDL ratio (r = 0.480,p = 0.002).ConclusionsFractal analysis is a novel, readily available, reproducible and inexpensive technique for the quantitative measurement of plaque irregularity. The correlation between low HDL levels and plaque FD suggests a role for HDL in the acquisition of morphologic features of plaque instability. Further studies are needed to validate the prognostic value of fractal analysis in carotid plaques evaluation.

Effects of spent mushroom Cordyceps militaris supplementation on apparent digestibility, rumen fermentation, and blood metabolite parameters of goats.

The objective of this experiment was to study the effects of dried spent mushroom Cordyceps militaris (SMCM) supplementation on digestibility, rumen fermentation, and blood metabolite parameters in goats. When the mushroom production and harvesting was complete, SMCM was collected fresh from a mushroom farm. Four 18-mo-old male crossbred (Thai Native × Anglo Nubian) goats with initial BW of 26.0 ± 1.40 kg were randomly assigned according to a 4 × 4 Latin square design to receive four different levels of SMCM at 0, 100, 200, and 300 g/d. There were quadratic effects (P < 0.06) on apparent digestibility of DM, OM, CP, NDF, and ADF among treatment groups, and greater values for the goats fed SMCM at 100 g/d were observed. A quadratic effect in energy intake (ME, Mcal/kg DM) (P = 0.02), with greater values for the goats fed SMCM at 100 g/d, was also observed. Rumen temperature was similar among groups (P = 0.23), whereas feeding of SMCM linearly decreased (P = 0.001) ruminal pH with increasing SMCM supplementation. Supplementing SMCM linearly decreased plasma concentration of cholesterol (P = 0.01), and there was also a tendency of reduction in plasma concentration of triglyceride (P = 0.10), with greater values for the goats fed SMCM at 100 g/d. There were quadratic effects on plasma of total protein, HgB, and MCHC among treatment groups. However, there were quadratic effects on fecal N (P = 0.04) and nitrogen retention (P = 0.07) based on g/d/animal or percentage of nitrogen retained (P = 0.01) among treatment groups, and greater values for the goats fed SMCM at 100 g/d were observed. Based on this experiment, it could be concluded that supplementing goat diets with SMCM at 100 to 200 g/d results in improved apparent digestibility of nutrients and blood metabolites, suggesting that SMCM has positive functions as a feed additive to improve energy substance metabolism and contribute to glyconeogenesis.

Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.

Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth. As expected, we found the differences in apoA-I expression led to changes in HDL particle size and protein cargo as well as plasma cholesterol concentrations. Fetal masses correlated directly with maternal plasma cholesterol and apoA-I concentrations, but placental masses and histology did not differ between groups of mice. There was no significant difference in glucose or amino acid transport to the fetus or in expression levels of the glucose (glucose transporter 1 and 2) or amino acid (sodium-coupled neutral amino acid transporter 1 and 2) transporters in whole placentas, although there was a trend for greater uptake of both nutrients in the whole fetal unit (fetus + placenta) of mice with greater apoA-I levels; significant differences in transport rates occurred when mice without apoA-I (knockout) vs. mice with apoA-I (wild-type and transgenic) were compared. Glucose tolerance tests were improved in the mice with the highest level of apoA-I, suggesting increased insulin-induced uptake of glucose by tissues of apoA-I transgenic mice. Thus, maternal HDL is associated with fetal growth, an effect that is likely mediated by plasma cholesterol or other HDL-cargo, including apolipoproteins or complement system proteins. A direct role of enhanced glucose and/or amino acid transport cannot be excluded.-Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., Woollett, L. A. Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.

Liver metabolism traits in two rabbit lines divergently selected for intramuscular fat

Intramuscular fat (IMF) has a large effect in the sensory properties of meat because it affects tenderness, juiciness and flavour. A divergent selection experiment for IMF in longissimus dorsi (LD) muscle was performed in rabbits. Since liver is the major site of lipogenesis in rabbits, the objective of this work is to study the liver metabolism in the lines of the divergent selection experiment. Intramuscular fat content, perirenal fat weight, liver weight, liver lipogenic activities and plasma metabolites related to liver metabolism were measured in the eighth generation of selection. Direct response on IMF was 0.34 g/100 g of LD, which represented 2.7 SD of the trait, and selection showed a positive correlated response in the perirenal fat weight. High-IMF line showed greater liver size and greater liver lipogenic activities of enzymes glucose-6-phosphate dehydrogenase and malic enzyme. We did not find differences between lines for fatty acid synthase lipogenic activity. With regard to plasma metabolites, low-IMF line showed greater plasma concentration of triglycerides, cholesterol, bilirubin and alkaline phosphatase than high-IMF line, whereas high-IMF line showed greater albumin and alanine transaminase concentrations than low-IMF line. We did not observe differences between lines for glucose, total protein and plasma concentrations. Phenotypic correlations between fat (IMF and perirenal fat weight) and liver traits showed that liver lipogenesis affects fat deposition in both, muscle and carcass. However, the mechanisms whereby liver lipogenesis affected IMF content remain to be clarified.

Assessment of Hepatic Cytochrome P450 3A Activity Using Metabolic Markers in Patients with Renal Impairment.

BackgroundThe renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of 4β-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers.MethodsSixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers (6β-OH-cortisol/cortisol, 6β-OH-cortisone/cortisone, 4β-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the 4β-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test.ResultsThere was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone as well as plasma 4β-OH-cholesterol and 4β-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate.ConclusionHepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.

Relationship between the nutritional state before the breeding period and the reproductive success in alpacas (Vicugna pacos) from the Chilean Puna

A poor nutritional state may explain the low fertility rates of domestic camelids from Puna herds. The objective of this study was to determine the relationship between the nutritional state of alpacas before the breeding period and their reproductive success. The body live weight (BLW) and body condition score (BCS; scale from 1-5) of 35 non-pregnant non-lactating alpacas from the Caquena bofedal in Chile were registered previous to the breeding period. In addition, blood samples were collected (heparinised tubes) to determine the plasma concentration of cholesterol (CHOD-PAP method), triglycerides (GPO-PAP method) and NEFA (enzymatic colorimetric method). Pregnancy was determined by trans-rectal ultrasonography (7.5 MHz, Samsung Madison, Korea) at the end of the breeding period. Data from Pregnant and Non-Pregnant groups were compared using Mann-Whitney U test (SPSS programme; P < 0.05). Pregnant (n=20) and Non-pregnant groups (n=15) had similar BLW (47.1 ± 8.8 compared to 52.8 ± 11.1 kg, respectively; P = 0.9), BCS (3.0 ± 0.4 compared to 3.1 ± 0.4, respectively; P = 0.5), plasma cholesterol (1.0 ± 0.4 compared to 0.9 ± 0.3 mmol/l, respectively; P =0.7), triglycerides (0.3 ± 0.1 compared to 0.4 ± 0.1 mmol/l, respectively; P = 0.3), and NEFA (0.6 ± 0.4 compared to 0.8 ± 0.6 mmol/l, respectively; P = 0.1) before the breeding period. NEFA values of both groups showed evidence of negative energy balance. The nutritional state of alpacas before the breeding period did not explain the differences obtained in their reproductive success.

Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the major phospholipid of circulating lipoproteins, is synthesized in human liver by two biologically diverse pathways: the cytidine diphosphocholine (CDP):choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways. Here, we used ESI-MS/MS both to characterize plasma PC compositions and to quantify metabolic fluxes of both pathways using stable isotopes in patients with severe ARDS and in healthy controls. Direct incorporation of methyl-D9-choline estimated CDP:choline pathway flux, while PEMT flux was determined from incorporations of one and two methyl-D3 groups derived from methyl-D9-choline. The results of MS/MS analysis showed significant alterations in plasma PC composition in patients with ARDS versus healthy controls. In particular, the increased overall methyl-D9-PC enrichment and, most importantly, the much lower methyl-D3-PC and methyl-D6-PC enrichments suggest increased flux through the CDP:choline pathway and reduced flux through the PEMT pathway in ARDS. To our knowledge, this study is the first to demonstrate significant plasma PC molecular compositional changes combined with associated alterations in the dynamics of PC synthetic pathways in patients with ARDS.