Serum Lipid Metabolites Research Articles

Metabolomic signature of genetic potential for muscularity in beef cattle

The aim of this study was to investigate the serum and meat metabolomic changes according to the genetic potential for muscularity of non-castrated Nellore males and its association with phenotypic traits. Forty-eight non-castrated Nellore males were separated into two groups based on their genetic potential for post-weaning muscularity: high (HM) and low (LM). Selection for muscularity did not cause noticeable differences in the traits evaluated during the finishing phase and after slaughter. However, several metabolites in meat and serum, have changed according to the muscularity group. HM animals presented an over-abundance of glycerol, glutamine, choline, methylhistidine, betaine, creatinine and methionine in serum, compared with their LM counterparts. Similarly, the meat samples of HM animals were rich in glucose-6-phosphate, lactate, pyruvate, creatinine, betaine, choline, glycerol and arginine relative to LM bulls. Inosine monophosphate was the only metabolite over-abundant in LM animals. In conclusion, the genetic potential for post-weaning muscularity did not affect performance during the finishing phase, carcass traits and meat quality. However, multivariate analysis shows that the genetic potential of muscularity can be correlated with serum lipid and protein metabolites, and with energy metabolism in meat, providing a footprint of cattle muscularity metabolism.

Effect of Dietary Supplementation of Fermented Pine Needle Extract on Productive Performance, Egg Quality, and Serum Lipid Parameters in Laying Hens.

Simple SummaryIn recent decades, the use of phytogenic feed additives as natural growth promoters has been substantially increased in the poultry industry. Fermented pine (Pinus densiflora) needle drink is used as a functional beverage in Korea due to its antioxidant effects. Therefore, the aim of the current study is to determine the effects of fermented pine needle extract on laying performance, egg quality, lipid parameters, and lipid oxidation of eggs in laying hens. Supplementation of fermented pine needle extract in laying hens’ diet improved productive performance and egg quality parameters.This study aimed to investigate the supplemental effects of fermented pine (Pinus densiflora) needle extract (FPNE) in laying hen diets on productive performance, egg quality, and serum lipid metabolites. A total of 108 40-week-old Hy-line brown laying hens were randomly assigned to one of the three dietary treatment groups: (1) basal diet + 0 mL FPNE/kg diet (CON), (2) basal diet + 2.5 mL FPNE/kg diet (T1), or (3) basal diet + 5 mL FPNE/kg diet (T2) for 6 weeks. Each group consisted of four replicates of nine hens each. Feed and water provided ad libitum. Results showed that dietary supplementation of FPNE increased egg production percentage (linear, p < 0.01 and quadratic, p < 0.05), egg mass (linear, p < 0.05), and feed intake (linear, p < 0.05) during the entire experimental period. In addition, dietary inclusion of FPNE significantly increased the eggshell color (linear, p < 0.01), egg yolk color (quadratic, p < 0.01), and eggshell breaking strength (linear, p < 0.05 and quadratic, p < 0.05) while the Haugh unit decreased (quadratic, p < 0.05). However, serum lipid profile did not differ among the dietary treatments (p > 0.05). Notably, antioxidant activity of egg yolk was improved by significantly decreasing the malondialdehyde content in egg yolks after 6 weeks of storage (linear, p < 0.001 and quadratic, p < 0.05). In summary, dietary inclusion of FPNE could improve laying performance and the antioxidant capacity of eggs.

Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice.

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

Time-Restricted Feeding Reduces the Detrimental Effects of a High-Fat Diet, Possibly by Modulating the Circadian Rhythm of Hepatic Lipid Metabolism and Gut Microbiota.

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism.Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints.Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p < 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p < 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes.Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.

Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD).

Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.

Quercitrin Ameliorates Hyperlipidemia and Hepatic Steatosis in Ovariectomized Mice.

Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women.

Profile of serum lipid metabolites of one-week-old goat kids depending on the type of rearing

BackgroundWeaning of goat kids immediately after birth and feeding them on bovine or heat-treated caprine colostrum, referred to as snatching, is considered an effective control measure in some infectious diseases. The study was carried out in one-week-old goat kids to gain insight into the profile of lipid metabolites and to investigate the influence of snatching on kids’ metabolism. Fifty-two goat kids born to 23 female goats were included in the study – 22 kids were weaned immediately after birth and kept isolated from their mothers; 30 remaining kids were left with their mothers for next 3 weeks so that they could nurse on dams’ milk at will. Blood was collected at the age of 1 week and serum was obtained by centrifugation. The concentration of lipid metabolites was determined with mass spectrometry using a commercial MxP® Quant 500 kit (Biocrates Life Sciences AG, Innsbruck, Austria).ResultsConcentration of 240 lipid metabolites belonging to 10 lipid classes was above the limit of detection of the assay. These lipid metabolites were quantified and included in the analysis. Concentration of 2 lipid classes (acyl-alkyl-phosphatidylcholines and ceramides) and 31 lipid metabolites (14 triacylglycerols, 5 acyl-alkyl-phosphatidylcholines, 2 diacylphosphatidylcholines, 1 lyso-phosphatidylcholine, 5 ceramides, 2 sphingomyelins, and 2 cholesterol esters) differed significantly between the two groups of kids.ConclusionSnatching of kids results in reduction of serum concentration of lipid metabolites, however, the magnitude of this phenomenon does not seem to be sufficient to negatively affect kids’ health condition. This study is the first in which the broad set of lipid metabolites of young ruminants was quantified using the novel metabolomic assay MxP® Quant 500 kit.

Lipoprotein A, combined with alanine aminotransferase and aspartate aminotransferase, contributes to predicting the occurrence of NASH: a cross-sectional study

BackgroundNonalcoholic steatohepatitis (NASH) progresses from simple nonalcoholic fatty liver (NAFL) and has a poor prognosis. Abnormal lipid metabolism is closely related to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to study the relationships between serum lipid metabolites and NASH, and to improve the early diagnosis of NASH.MethodsThis study included 86 NAFLD patients (23 NASH and 63 NAFL), and 81 unaffected individuals as controls from West China Hospital between October 2018 and May 2019. With lipid metabolites as the focus of the study, the differences in lipid metabolites were compared between the control group, NAFL patients, and NASH patients. Logistic regression analysis was used to examine the risk factors of NASH. Finally, receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of the metabolites in NASH prediction.ResultsThe levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipoprotein A (LPA) increased with the severity of NAFLD. In NAFLD patients, LPA (OR:1.61; 95%CI: 1.03–2.52) was a potential risk factor for NASH, and ROC analysis showed that the combination of LPA, ALT, and AST had a greater predictive efficiency for NASH.ConclusionsAbnormal apolipoprotein/lipoprotein is closely related to lipid metabolism disorder in patients with NAFLD. In NAFL, the combination of LPA, ALT, and AST contributes to predicting the occurrence of NASH. LPA may be a potential biomarker and therapeutic target for diagnosing and treating NASH.

Serum Acylglyceride Metabolites are Negatively Associated with Muscle Oxidative Capacity, but Not with Physical Activity, in Severe COPD

RATIONALEChronic obstructive pulmonary disease (COPD) is associated with altered metabolism and body composition that accompany worse outcomes. Serum lipid metabolites are dysregulated in COPD (e.g. sphingolipids, polyunsaturated fatty acids, ceramides). Loss of skeletal muscle mitochondrial oxidative capacity is implicated in mediating the association between hyperlipidemia and COPD. As both oxidative capacity and physical activity are negatively associated with COPD severity, this study aimed to determine whether lipid dysregulation in COPD was associated with muscle oxidative capacity and/or physical inactivity. We hypothesized that alteration of lipid metabolites in COPD would be associated with muscle oxidative capacity, independent of pulmonary function.METHODSCurrent and former smokers with COPD (n=44, FEV1=61±4%pred) and without COPD (CON) (n=63, FEV1=93±2%pred) volunteered. Untargeted prime and lipid metabolites were measured using liquid chromatography and mass spectrometry. Medial gastrocnemius oxidative capacity was assessed at rest from the recovery rate constant (k) of muscle oxygen consumption using near‐infrared spectroscopy. Daily step count and physical activity (average vector magnitude units (VMU)/min) were measured over 7 days by waist‐worn triaxial accelerometer.RESULTSThe k value (1.12±0.05 vs. 1.68±0.06 min−1, P&lt;0.0001) and VMU/min (170±26 vs. 450±50 VMU/min, P=0.004) were lower in severe COPD (FEV1&lt;50%pred, n=14–16) compared with CON. 129 prime metabolites and 470 lipids with known identity were quantified. Using sex as a covariate, lipidomics revealed that 24 lipids (19 sphingomeylins) were differentially expressed in COPD, consequent to a diminished sex difference of sphingomeylins in COPD (FDR&lt;0.05). Total, and some individual, fatty acid concentrations were greater in severe COPD than in CON (FDR&lt;0.05). After adjusting for FEV1%pred, we observed that grouped diacylglyceride (DG; Spearman’s rho = −0.745, FDR=0.03) and triacylglyceride (TG; rho = −0.811, FDR=0.01) were negatively associated with muscle oxidative capacity, but not physical activity, in severe COPD.DISCUSSIONWe found 24 lipids, including 19 sphingomyelins, increased in COPD with sex as covariant; and that sex‐dependent differences in sphingomyelin in CON were diminished COPD. This may contribute to more rapid progression of COPD in women than in men. Strong negative associations between blood lipids and muscle oxidative capacity, but not physical activity, suggest that impaired mitochondrial function may play a role in the accumulation of serum aclyglycerides in severe COPD. These data provide a strong rationale for targeting mitochondrial deficits by exercise training, or other means, to improve outcomes in COPD.Support or Funding InformationShenzhen Technology University (RL); VA MERT I01 BX00435, R01HL111437, R01HL129727 (TKH); Swiss National Science Foundation P300P3_151705 (AA); ATS‐2014‐03, Pulmonary Education and Research Foundation (HBR); R01HL089856; R01HL089897; UL1TR000124.

Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice.

Simple SummaryMilk secreted from mammary glands is an important nutrition source for offspring after parturition. Mammary gland development and lactation ability have important effects on the growth and health of the offspring. Many studies have demonstrated that external factors, including the environment and nutrition influence the development of mammary glands. Lauric acid is a fatty acid that has many nutritional and physiological properties. In this study, we investigated the effects of dietary supplementation of lauric acid on lactation function and mammary gland development in lactating mice. We found that dietary supplementation of lauric acid during lactation might enhance the mammary development to promote the lactation function of mice. Through the study of mice, we hoped that the results could be applied to animal feed development and animal breeding production.Our previous studies demonstrated that lauric acid (LA) stimulated mammary gland development during puberty. However, the roles of LA on lactation in mice remain indeterminate. Thus, the aim of this study was to investigate the effects of dietary LA supplementation on lactation functioning and to study the potential mechanisms during lactation. in vivo, there was no effect of 1% LA dietary supplementation during lactation on the feed intake or body weight of breast-feeding mice. However, maternal LA supplementation significantly expanded the number of mammary gland alveoli of mice during lactation and the average body weight of the offspring, suggesting that LA supplementation enhanced the development and lactation function of the mammary glands. in vitro, 100 μM of LA significantly increased the content of triglycerides (TG) in the cell supernatant of induced HC11 cells, however, with no effect on the expression of the genes associated with fatty acid synthesis. LA also activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. LA dietary supplementation significantly expanded the serum levels of lipid metabolites, including sphingomyelin and other metabolites with the sn-2 position of C12 and sn-1 position of C18 in the TG of the lactating mice. Taken together, dietary supplementation of LA during lactation could promote the lactation function of mice, which might be related to increasing the development of the mammary glands and alternation of serum lipid metabolites. These findings provided more theoretical and experimental basis for the application of lauric acid in the development of mammary glands and lactation function of lactating animals.

Anti-depressive effects of Kai-Xin-San on lipid metabolism in depressed patients and CUMS rats using metabolomic analysis

Ethnopharmacological relevanceIn this study, in order to explore potential depressive biomarkers and potential regulatory targets of KXS on depression, we assessed the effects of Kai-Xin-San (KXS) on lipid metabolism in depressed patients (DPs) and rats exposed to chronic and unpredictable mild stress (CUMS). Materials and methodsSerum samples were collected from DPs, DPs with 8 weeks of KXS treatment (KXS) and healthy controls (HCs), and non-targeted lipidomics was used to analyze the effect of KXS on serum lipid metabolites in DPs. Based on UPLC-Q-TOF/MS technology, differential metabolites were validated in a large sample size. The potential regulatory network of KXS was analyzed by bioinformatic analysis, and the expressions of proteins in serum were verified using western boltting analysis. Moreover, effects of KXS on serum lipid and lipid metabolism-related hormone levels in CUMS rats were detected by enzyme-linked immunosorbent assay and enzymatic method. ResultsWe validated that the levels of six serum lipid metabolites (N-Desmethylcitalopram (HMDB14021), PC(14:1(9Z)/24:0) (HMDB07926), PC(P-18:1(11Z)/20:0) (HMDB11281), PC(O-18:0/20:4(8Z,11Z,14Z,17Z)) (HMDB13420), PC(16:0/P-18:0) (HMDB07995) and PC(16:0/P-18:1(11Z)) (HMDB07996)) between HC/DP groups and between DP/KXS groups were significantly different. Among these six metabolites, HMDB07995, HMDB07996, HMDB13420 and HMDB11281 were highly sensitive and specific for depression and KXS treatment by receiver operating characteristic (ROC) curve analysis. matrix metalloproteinases (MMPs) including MMP2 and MMP9, apolipoproteins (Apo) including APOA1 and APOC1 were up-regulated and apolipoproteins (Apo) including APOB, APOD and APOE, phospholipid transfer protein (PLTP), Paraoxonase 1 (PON1) were down-regulated in DPs, and KXS treatment could reverse these changes. In CUMS rats, KXS could increase the open-field score, sucrose preference and body weight, and reduce immobility time. Furthermore, KXS increased the serum levels of the above-mentioned six metabolites, reduced serum total cholesterol (TCH), triglyceride (TG) and free fatty acid (FFA) levels and increased the serum high-density lipoprotein cholesterol (HDL-C) level in CUMS rats. In addition, leptin and ghrelin were down-regulated by KXS. ConclusionsThe results suggested that KXS exerted antidepressant effects by regulating the signaling pathways involved in lipid metabolism disorders. The lipid metabolites might be potential biomarkers of depression and possible targets for KXS-based treatment of depression.

Lipid Catabolism in Starved Yak Is Inhibited by Intravenous Infusion of β-Hydroxybutyrate.

Simple SummaryYak, which is the predominant and semi-domesticated livestock on the Qinghai-Tibet Plateau, suffers severe starvation and body weight reduction in the cold season because of the harsh highland environment. Lipids are important energy sources to starvation animals. β-hydroxybutyrate (BHBA) that is derived from lipid decomposition as the primary ketone body is with the function not only to provide energy for animals as energy materials, but also regulate lipid metabolism as signaling molecular. However, the effects of starvation and BHBA on lipid metabolism and its mechanism are still unclear for ruminant animals. Herein, we investigated the effects of starvation and intravenous infusion of BHBA solution on Yak growth, serum biochemistry, hormones, subcutaneous adipocyte morphology, fatty acid composition, activity of enzymes related to lipid metabolism, and signal pathway. The results showed that starvation promoted lipid catabolism and BHBA infusion up-regulated the mRNA expression of receptor GPR109A in subcutaneous adipose tissue, inhibited the Cyclic adenosine monophosphate(cAMP)/Protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signaling pathway, and inhibited lipolysis. Our study was beneficial for enriching the nutrition regulation theory of yaks and improving their growth potential.Lipid is the chief energy source for starved animals. β-hydroxybutyrate (BHBA) is the main ketone body produced by lipid decomposition. In Chinese hamster ovary (CHO) cell experiment, it was found that BHBA could be used not only as an energy substance, but also as a ligand of GPR109A for regulating lipid metabolism. However, whether BHBA can regulate lipid metabolism of yaks, and its effective concentration and signal pathway are not clear. This study investigated the effects and mechanism of starvation and BHBA on the lipid metabolism of yak. Eighteen male Jiulong yaks were selected and then randomly divided into three groups: normal feeding group (NG), starvation group (SG), and starvation with BHBA infusion group (SBG). The yaks in the NG group were freely fed during the trial, while the yaks in the SG and SBG groups fasted; from 7th to 9th days of the experiment, the NG and SG were infused continuous with 0.9% normal saline and SBG was infused 1.7 mmol/L BHBA solution respectively. The blood samples were collected on the 0th, 1st, 3rd, 5th, 7th, and 9th day of experiment. The subcutaneous adipose tissue of all the yaks in this study were taken from live bodies after infusion. Serum glucose, lipid metabolites, hormone concentrations, and mRNA and protein expressions of key factors of lipid metabolism and signaling pathway in subcutaneous adipose tissue were measured. The results showed that, as compared with NG, starvation significantly reduced the body weight of yak in SG, and significantly increased the concentration of BHBA in serum and the mRNA expression of PKA and CREB1 in subcutaneous adipose tissue, while the mRNA expression of MEK, PKC, ERK1/2, the area of adipocytes, and the proportion of saturated fatty acid were decreased. Whereas, further increase of BHBA concentration through infusion promoted the mRNA expression of GPR109A receptor in the subcutaneous adipose tissue of SBG, inhibited the mRNA expression of AC and PKA, and decreased the phosphorylation protein abundance of CREB1, and significantly increased the diameter and area of adipocytes. These findings suggest that starvation led to enhanced lipid catabolism in yaks. An increasing BHBA concentration could increase the mRNA expression of GPR109A receptor in subcutaneous adipose tissue and inhibit the cAMP/PKA/CREB signaling pathway and lipid decomposition.

Regulation of serum lipidomics and amino acid profiles of rats with acute myocardial ischemia by Salvia miltiorrhiza and Panax notoginseng herb pair

BackgroundSalvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely used in traditional Chinese medicine for a long history to prevent and treat the coronary heart disease. However, its protective mechanisms against myocardial ischemia during coronary heart disease remain not well-understood. PurposeIn this study, we aimed to explore the protective mechanisms of DQ on myocardial ischemia from the perspective of serum lipidomics and amino acids (AAs). MethodsRats were orally administrated with low-dose DQ (L-DQ, 0.24 g/kg) and high-dose DQ (H-DQ, 0.96 g/kg) for two weeks and subcutaneously injected with isoproterenol (ISO, 65 mg/kg) for two consecutive days (13th and 14th days) to induce acute myocardial ischemia (AMI). Heart histopathology and serum biochemical indices were examined. The specifically altered serum lipid metabolites were profiled via lipidomics approach, while serum AA profiles were analyzed using UHPLC-TQ-MS/MS. ResultsCardiac marker enzymes (CK, CK-MB, LDH and cTn-I) were significantly upregulated in AMI rats with some of which significantly dropped to normal level in L- and H-DQ groups. Serum TC, TG, HDL, LDL, VLDL and FFA were improved in AMI rats treatment with L- and H-DQ. Further, the PCA based on lipidomics showed serum lipid metabolites in L- and H-DQ groups were closer to control group than that in model group. Compared with model group, H-DQ pretreatment significantly reduced SM (d34:1) and CE (20:4), and increased FA (20:5), PC (26:1), TG (56:9), TG (54:7), MG (17:0), Cer (d32:0) and Cer (d34:0), whereas L-DQ significantly alleviated the perturbed levels of CE (20:4), FA (20:5), MG (17:0), and SM (d34:1). Moreover, there was a significant increment for leucine, isoleucine, valine, phenylalanine, lysine and glutamate but a significant reduction for tryptophan in the serum of rats in model group as compared to control group. Intriguingly, H-DQ could significantly decrease the levels of glutamate, lysine, isoleucine, and BCAAs (the sum of leucine, isoleucine and valine) after AMI, while L-DQ had no significant effects on the above altered AAs. The Western blotting results implied that H-DQ could promote the myocardial BCAA catabolism in AMI rats by activation of BCKDHA, whereas by inhibition of BCKDHK. ConclusionThis study presents evidence for the therapeutic effects of DQ on AMI injury, in part, via co-regulating lipid and AA metabolisms.

Effects of Activated Charcoal-Herb Extractum Complex on Antioxidant Status, Lipid Metabolites and Safety of Excess Supplementation in Weaned Piglets.

Simple SummaryWeaning is the most significant event in the life of pigs and pigs must cope with the sudden disruption of social interaction with sows and litters and pressure to adapt to new environments that may impair the growth performance and health status of piglets. Weaning can induce oxidative stress and disturb the balance of lipid metabolism in pigs. In this study, we innovatively evaluated a complex of activated charcoal and Chinese herb extractum (CHC) in weaning pigs on antioxidant status, serum lipid metabolites and safety supplementation in weaning pigs. This complex combines functions of active charcoal in absorption of toxins and the Chinese medicinal herbs in antioxidant capacity. The results demonstrated a promising additive of this complex CHC in future applications. This complex may be a good nutritional supplement to use in swine production.This study was aimed at evaluating the effects of activated charcoal-herb extractum complex (CHC) on antioxidant status, serum lipid metabolites and its safety supplement in weaning piglets. In experiment 1, a total of 216 piglets (Duroc × Landrace × Large White) weaned at 28 days of age with initial body weight of 8.55 ± 1.18 kg were assigned randomly to six treatment groups. each treatment group had six pens, with six pigs per pen. Pigs were fed a corn-soybean meal-based diet supplemented with 500, 1000, 1500 or 2000 mg kg−1 of CHC over two 14-d periods. Diets supplemented with 0 and 1000 mg kg−1 of montmorillonite (MMT) were set as the negative and positive controls, respectively. In experiment 2, pigs (n = 108) weaned at 28 days of age with initial body weight of 8.58 ± 0.04 kg were randomly assigned to three treatment groups. Each treatment group had six pens, with six pigs per pen. Pigs were fed a corn-soybean meal-based diet supplemented with 0, 1000 or 10,000 mg kg−1 of CHC over two 14-d periods. In experiment 1, on day 14, supplementation with CHC significantly decreased very low-density lipoprotein (VLDL) concentration while they decreased low-density lipoprotein (LDL) concentration on d 28, CHC at 500, 1000 or 1500 mg kg−1 significantly increase high-density lipoprotein (HDL) concentration. Supplementation with 500 or 1000 mg kg−1 CHC reduced serum malondialdehyde (MDA) concentration during the entire experimental period and increased the concentration of serum total superoxide dismutase (T-SOD) on d 14. CHC at 500 or 1000 mg kg−1 significantly reduced the liver MDA concentration and increased liver T-SOD concentration. In experiment 2, increased ADG was obvious during the first 14 days and the whole period in 1000 mg kg−1 supplemented pigs, similarly F: G was lowest in the first 14 days. There was no difference in growth performance, visceral index, haematological and serum biochemical parameters and visceral organs morphology between pigs fed 10,000 mg kg−1 of CHC and control. Together, 500 to 1000 mg kg−1 CHC was confirmed to improve antioxidant status, and serum lipid metabolites in this study and excess supplementation of CHC is safe in weaning piglets.

449 – High Fat Ketogenic Diet Decreases Serum Lipid Metabolites in Healthy Dogs

449 – High Fat Ketogenic Diet Decreases Serum Lipid Metabolites in Healthy Dogs

Effects of Personal Short-Term Exposure to Ambient Ozone on Blood Pressure and Vascular Endothelial Function: A Mechanistic Study Based on DNA Methylation and Metabolomics.

Short-term exposure to ambient ozone is associated with adverse cardiovascular effects, with inconsistent evidence on the molecular mechanisms. We conducted a longitudinal panel study among 43 college students in Shanghai to explore the effects of personal ozone exposure on blood pressure (BP), vascular endothelial function, and the potential molecular mechanisms. We measured real-time personal ozone exposure levels, serum angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1), and locus-specific DNA methylation of ACE and EDN1 (coding ET-1). We used an untargeted metabolomic approach to explore potentially important metabolites. We applied linear mixed-effect models to examine the effects of ozone on the above biomarkers. An increase in 2 h-average ozone exposure was significantly associated with elevated levels of BP, ACE, and ET-1. ACE and EDN1 methylation decreased with ozone exposure, but the magnitude differed by genomic loci. Metabolomics analysis showed significant changes in serum lipid metabolites following ozone exposure that are involved in maintaining vascular endothelial function. Our findings suggested that acute exposure to ambient ozone can elevate serum levels of ACE and ET-1, decrease their DNA methylation, and alter the lipid metabolism, which may be partly responsible for the effects of ozone on BP and vascular endothelial function.

Effects of dietary supplemental bile acids on performance, carcass characteristics, serum lipid metabolites and intestinal enzyme activities of broiler chickens.

The objective of the present study was to evaluate the effect of bile acids derived from swine on the growth performance, carcass traits, serum lipid metabolites and intestinal enzyme activities in broiler chickens. Four hundred thirty-two 1-day-old Arbor Acres male broilers were randomly assigned to 4 treatments with 6 replicates of 18 chicks each for 42 d. The experimental treatments received a corn-soybean basal diet containing lard and were as follows: 0 (control), 40 mg, 60 mg, and 80 mg bile acids/kg of diet. Dietary of inclusion bile acids significantly increased average daily gain and decreased feed to gain ratio from d 21 to d 42 (P < 0.01). However, average daily feed intake was unaffected by dietary supplementation with bile acids. The dressing percentage and the percentage of thigh muscle in the carcass were notably (P < 0.01) higher for broilers fed diets supplemented with 60 and 80 mg/kg bile acids. In contrast, abdominal fat weight was reduced significantly (P < 0.01). In 42-day-old broilers, serum triglyceride, high density lipoprotein and low density lipoprotein concentrations were unaffected (P > 0.05) by bile acids supplementation. Supplementation with 60 and 80 mg/kg significantly increased the activity of duodenum lipase and lipoprotein lipase on d 21 and d 42, as well as decreased the activity of hormone sensitive lipase on d 42. Supplementation of diets with 60 and 80 mg/kg of bile acid can effectively enhance the activity of intestinal lipase and lipoprotein lipase and improve growth performance and carcass traits of broilers.

Prospective serum metabolomic profile of prostate cancer by size and extent of primary tumor.

Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1–20). LC/MS-GC/MS identified 625 known compounds, and logistic regression estimated odds ratios (ORs) associated with one-standard deviation differences in log-metabolites. N-acetyl-3-methylhistidine, 3-methylhistidine and 2′-deoxyuridine were elevated in men with T2 cancers compared to controls (ORs = 1.38–1.79; 0.0002 ≤ p ≤ 0.01). By contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl-linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and inositol 1-phosphate (ORs = 0.49–0.60; 0.000017 ≤ p ≤ 0.003). Secondary bile acid lipids, sex steroids and caffeine-related xanthine metabolites were elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit qualitatively different metabolite profiles years in advance of diagnosis that may represent etiologic factors, molecular patterns reflective of distinct primary tumors, or a combination of both.

Combined Clinical Phenotype and Lipidomic Analysis Reveals the Impact of Chronic Kidney Disease on Lipid Metabolism.

Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.

Effects of different organic acids on performance, ileal microflora, and phosphorus utilization in laying hens fed diet deficient in non-phytate phosphorus

The present study was conducted to investigate the effect of dietary supplementation of organic acids (OA) on performance and phytate phosphorus utilization in laying hens fed diets with different non-phytate phosphorus (NPP) levels. A total of 240 Hy-Line W-36 laying hens, 32-wk-old, were randomly allocated into the 8 dietary treatments with 5 cage replicates of 6 birds each. The main trial period lasted for 10 wk (34–44 wk of age), following a 2 wk adaptation period (32–34 wk of age). Dietary treatments consisted of a 4×2 factorial arrangement of treatments, including 4 supplemental OA (control, citric, butyric, or fumaric acids, 5g/kg of diet) and 2 different NPP levels (60 or 100% of Hy-Line W-36 recommended values). Results showed that dietary OA supplementation increased (P<0.05) egg production percentage, with the greatest values assigned to the hens fed citric and butyric acids-supplemented diets. Reducing dietary NPP level resulted in a marked decrease in egg production in control hens, while OA supplementation of the NPP-deficient diet could maintain egg production and egg mass, resulted in the significant (P<0.05) OA×NPP interactions. Although feed intake was not affected by dietary treatments, supplemental OA improved (P<0.05) feed conversion ratio in NPP-deficient hens (OA×NPP, P<0.05). Dietary OA supplementation increased (P<0.05) eggshell thickness; however, it had no marked impact on shell breaking strength. Serum lipid metabolites were influenced by dietary OA supplementation, so that supplemental OA decreased (P<0.01) serum cholesterol level and increased (P<0.001) serum high-density lipoproteins. Feeding the NPP-deficient diet decreased (P<0.01) tibia ash and increased (P<0.001) serum alkaline phosphatase activity. On the other hand, dietary supplementation of fumaric acid increased (P<0.01) tibial ash and Ca contents compared to the control hens. Tibia P content was lower (P<0.05) in hens fed the NPP-sufficient diet. Inclusion of citric acid into the NPP-deficient diet increased tibia P, resulted in a significant (P<0.001) OA×NPP interaction. Dietary supplementation of OA reduced (P<0.01) ileal enumeration of Salmonella, and the lowest (P<0.05) Escherichia coli count was observed for hens supplemented with butyric acid. The present findings indicate that dietary OA supplementation can increase egg production, egg mass, and eggshell thickness in hens fed the NPP-deficient diet. The beneficial impact of citric acid on tibia P content of NPP-deficient hens suggests that supplemental OA could improve P utilization even in young laying hens.