Pharmacokinetics of soy-derived lysophosphatidylcholine compared with that of glycerophosphocholine: a randomized controlled trial.

Lysophosphatidylcholine (LPC) is present in various foods and contains a choline moiety such as in glycerophosphocholine (GPC). However, the potential of LPC as a choline source remains unclear. This study investigated the single-dose pharmacokinetics of 480 mg soy-derived LPC in 12 healthy men compared with that of either soy oil with the same lipid amount (placebo) or GPC with the same choline amount. Both LPC and GPC supplementation increased plasma choline, serum phospholipid, and serum triglyceride concentrations, but neither of them significantly elevated plasma trimethylamine N-oxide concentration. In addition, although the intake of LPC slightly increased plasma LPC16:0, LPC18:2, and total LPC concentrations, their concentrations remained within physiological ranges. No adverse events were attributed to the LPC supplementation. To the best of our knowledge, this study is the first to compare LPC and GPC pharmacokinetics in humans and shows that LPC can be a source of choline.

Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest.

OBJECTIVE: Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC-DHA), was significantly decreased in plasma post-CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC-DHA supplementation on the brain post-CA. METHODS: We first evaluated associations between the plasma level of LPC-DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC-DHA supplementation. RESULTS: We found that decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased levels of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC-DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. INTERPRETATION: The observed neuroprotection accompanied with normalized brain LPC-DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC-DHA post-CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC-DHA for brain damage after CA. ANN NEUROL 2022;91:389-403.

Ginsenosides regulation of lysophosphatidylcholine profiles underlies the mechanism of Shengmai Yin in attenuating atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) preparation, Shengmai Yin (SMY), is widely applied in cardiovascular disease treatments. However, the pharmacological mechanism of its therapeutic effects has not been fully clarified. AIM OF THIS STUDY: This study aimed to clearly define the efficacy and underlying mechanism of SMY and its active components in protecting against atherosclerosis. MATERIALS AND METHODS: The pharmacological effects of SMY and its components were evaluated upon a mouse hypercholesteremia model induced by a high cholesterol diet (HCD) for 12 weeks and Apoe-/- mice, a mouse atherosclerosis model. Pathological indicators including serum cholesterol levels, cytokines and histological changes in aortic root plaques were assessed. Untargeted metabolomic, untargeted lipidomic and targeted lipidomic changing profiles were investigated to clarify pharmacological mechanisms. RESULTS: SMY and red ginseng crude extracts (GE) significantly decreased the serum cholesterol levels in hypercholesteremia mice and reduced the aortic root plaque areas and exerted antiatherogenic efficacy in Apoe-/- mice. Moreover, total red ginseng saponin extracts (TGS) showed the most apparent improvement on maintaining lipid homeostasis, representing the effects of red ginseng in SMY on atherosclerosis treatment. Mechanically, TGS inhibited serum secreted phospholipase A2 (sPLA2) activity and lowered the serum levels of lysophosphatidylcholine (lysoPC), which is a risk factor for atherosclerosis. CONCLUSIONS: Our findings revealed that ginsenosides from SMY exerted therapeutic effects on atherosclerosis by maintaining lipid homeostasis including cholesterol and lysoPCs.

Plasma Lipidomics Reveals Insights into Anti-Obesity Effect of Chrysanthemum morifolium Ramat Leaves and Its Constituent Luteolin in High-Fat Diet-Induced Dyslipidemic Mice.

The Chrysanthemum morifolium Ramat (CM) is widely used as a traditional medicine and herbal tea by the Asian population for its health benefits related to obesity. However, compared to the flowers of CM, detailed mechanisms underlying the beneficial effects of its leaves on obesity and dyslipidemia have not yet been elucidated. Therefore, to investigate the lipidomic biomarkers responsible for the pharmacological effects of CM leaf extract (CLE) in plasma of mice fed a high-fat diet (HFD), the plasma of mice fed a normal diet (ND), HFD, HFD plus CLE 1.5% diet, and HFD plus luteolin 0.003% diet (LU) for 16 weeks were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate analysis. In our analysis, the ND, HFD, CLE, and LU groups were clearly differentiated by partial least-squares discriminant analysis (PLS-DA) score plots. The major metabolites contributing to this differentiation were cholesteryl esters (CEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), ceramides (CERs), and sphingomyelins (SMs). The levels of plasma CEs, LPCs, PCs, SMs, and CERs were significantly increased in the HFD group compared to those in the ND group, and levels of these lipids recovered to normal after administration of CLE or LU. Furthermore, changes in hepatic mRNA expression levels involved in the Kennedy pathway and sphingolipid biosynthesis were also suppressed by treatment with CLE or LU. In conclusion, this study examined the beneficial effects of CLE and LU on obesity and dyslipidemia, which were demonstrated as reduced synthesis of lipotoxic intermediates. These results may provide valuable insights towards evaluating the therapeutic effects of CLE and LU and understanding obesity-related diseases.

Ginseng-Induced Changes to Blood Vessel Dilation and the Metabolome of Rats.

Ginseng consumption has been shown to prevent and reduce many health risks, including cardiovascular disease. However, the ginseng-induced changes in biofluids and tissue metabolomes associated with blood health remain poorly understood. In this study, healthy rats were orally administered ginseng extracts or water for one month. Biofluid and tissue metabolites along with steroid hormones, plasma cytokines, and blood pressure factors were determined to elucidate the relationship between ginseng intake and blood vessel health. Moreover, the effect of ginseng extract on blood vessel tension was measured from the thoracic aorta. Ginseng intake decreased the levels of blood phospholipids, lysophosphatidylcholines and related enzymes, high blood pressure factors, and cytokines, and induced vasodilation. Moreover, ginseng intake decreased the level of renal oxidized glutathione. Overall, our findings suggest that ginseng intake can improve blood vessel health via modulation of vasodilation, oxidation stress, and pro-inflammatory cytokines. Moreover, the decrease in renal oxidized glutathione indicated that ginseng intake is positively related with the reduction in oxidative stress-induced renal dysfunction.

Impact of Treatment with RUTF on Plasma Lipid Profiles of Severely Malnourished Pakistani Children.

(1) Background: Little is known on impacts of ready-to-use therapeutic food (RUTF) treatment on lipid metabolism in children with severe acute malnutrition (SAM). (2) Methods: We analyzed glycerophospholipid fatty acids (FA) and polar lipids in plasma of 41 Pakistani children with SAM before and after 3 months of RUTF treatment using gas chromatography and flow-injection analysis tandem mass spectrometry, respectively. Statistical analysis was performed using univariate, multivariate tests and evaluated for the impact of age, sex, breastfeeding status, hemoglobin, and anthropometry. (3) Results: Essential fatty acid (EFA) depletion at baseline was corrected by RUTF treatment which increased EFA. In addition, long-chain polyunsaturated fatty acids (LC-PUFA) and the ratio of arachidonic acid (AA)/linoleic acid increased reflecting greater EFA conversion to LC-PUFA, whereas Mead acid/AA decreased. Among phospholipids, lysophosphatidylcholines (lyso.PC) were most impacted by treatment; in particular, saturated lyso.PC decreased. Higher child age and breastfeeding were associated with great decrease in total saturated FA (ΣSFA) and lesser decrease in monounsaturated FA and total phosphatidylcholines (ΣPC). Conclusions: RUTF treatment improves EFA deficiency in SAM, appears to enhance EFA conversion to biologically active LC-PUFA, and reduces lipolysis reflected in decreased ΣSFA and saturated lyso.PC. Child age and breastfeeding modify treatment-induced changes in ΣSFA and ΣPC.

Lipidomic characterization of exosomes isolated from human plasma using various mass spectrometry techniques.

Ultrahigh-performance supercritical fluid chromatography - mass spectrometry (UHPSFC/MS), ultrahigh-performance liquid chromatography - mass spectrometry (UHPLC/MS), and matrix-assisted laser desorption/ionization (MALDI) - MS techniques were used for the lipidomic characterization of exosomes isolated from human plasma. The high-throughput methods UHPSFC/MS and UHPLC/MS using a silica-based column containing sub-2 µm particles enabled the lipid class separation and the quantitation based on exogenous class internal standards in <7 minute run time. MALDI provided the complementary information on anionic lipid classes, such as sulfatides. The nontargeted analysis of 12 healthy volunteers was performed, and absolute molar concentration of 244 lipids in exosomes and 191 lipids in plasma belonging to 10 lipid classes were quantified. The statistical evaluation of data included principal component analysis, orthogonal partial least square discriminant analysis, S-plots, p-values, T-values, fold changes, false discovery rate, box plots, and correlation plots, which resulted in the information on lipid changes in exosomes in comparison to plasma. The major changes were detected in the composition of triacylglycerols, diacylglycerols, phosphatidylcholines, and lysophosphatidylcholines, whereby sphingomyelins, phosphatidylinositols, and sulfatides showed rather similar profiles in both biological matrices.

Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol.

Docosahexaenoic acid (DHA) is highly concentrated in the brain, and its deficiency is associated with several neurological disorders including Alzheimer's disease. However, the currently used supplements do not appreciably enrich brain DHA, although they enrich most other tissues. We tested the hypothesis that the ability of the dietary carrier to augment brain DHA depends upon the generation of DHA-lysophosphatidylcholine (LPC), the preferred carrier of DHA across the blood brain barrier. We compared the efficacy of DHA-triacylglycerol (TAG), di-DHA phosphatidylcholine (PC) and DHA-LPC to enrich brain DHA following their gavage to normal rats for 30 days, all at a dose of 10 mg DHA/day. The results show that DHA from TAG, which is released as free DHA or monoacylglycerol during digestion and is absorbed as TAG in chylomicrons, was incorporated preferentially into adipose tissue and heart but not into brain. In contrast, LPC-DHA increased brain DHA by up to 100% but had no effect on adipose tissue. Di-DHA PC, which generates both free DHA and LPC-DHA during the digestion, enriched DHA in brain, as well as in heart and liver. Brain-derived neurotrophic factor was increased by di-DHA PC and DHA-LPC, but not by TAG-DHA, showing that enrichment of brain DHA correlated with its functional effect. We conclude that dietary DHA from TAG or from natural PC (sn-2 position) is not suitable for brain enrichment, whereas DHA from LPC (at either sn-1 or sn-2 position) or from sn-1 position of PC efficiently enriches the brain and is functionally effective.

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients.

We examined the effect of high fat oral nutritional supplement (HFS) on the nutritional status, oral intake, and serum metabolites of postoperative pancreaticobiliary cancer patients. Pancreaticobiliary cancer patients were voluntarily recruited. The HFS group received postoperative oral high fat supplementation (80% of total calories from fat; n = 12) until discharge; the control group (non-HFS; n = 9) received none. Dietary intake, anthropometry, blood chemistry, nutritional risk index (NRI), and serum metabolites analyzed by liquid chromatography tandem mass spectrometry were evaluated. Overall, cumulative caloric supply via parental and oral/enteral routes were not different between groups. However, oral fat intake, caloric intake, and NRI scores of the HFS group were higher than those of the non-HFS group with increased oral meal consumption. Oral caloric, fat, and meal intakes correlated with NRI scores. Metabolomics analysis identified 195 serum metabolites pre-discharge. Oral fat intake was correlated with 42 metabolites relevant to the glycerophospholipid pathway. Oral high fat-specific upregulation of sphingomyelin (d18:1/24:1), a previously reported pancreatic cancer-downregulated metabolite, and lysophosphatidylcholine (16:0) were associated with NRI scores. Provision of HFS in postoperative pancreatic cancer patients may facilitate the recovery of postoperative health status by increasing oral meal intake, improving nutritional status, and modulating serum metabolites.

Gender- and dose-related metabolome alterations in rat offspring after in utero and lactational exposure to PCB 180.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that are still causing potentially harmful effects to humans and wildlife. While the adverse health effects of PCBs have been extensively studied for decades, little is known about the effects specifically caused by the less potent, yet abundant non-dioxin-like congeners (NDL-PCBs). Here a non-targeted metabolic profiling of rat offspring exposed in utero and lactationally to total doses of 0, 300 or 1000 mg/kg body weight of ultrapure PCB 180 is reported. Serum samples from 5 male, and 5 female offspring from each group taken 12 weeks after birth were analyzed using UHPLC-qTOF-MS system, and subsequent metabolite alterations were studied. Statistical analysis revealed gender and dose-dependent alterations in serum metabolite levels at doses that did not adversely influence maternal or offspring body weight development. Male rats exhibited a higher number of altered metabolites, as well as stronger dose-dependency. A total of 51 metabolites were identified based on spectral matching. Most notably, 20 of these were glycerophospholipids, mainly lysophosphocholines with systematically decreased concentrations especially in the high-dose males. Other major metabolite groups include amino acids, their derivatives and carnitines. Our findings are consistent with the earlier reported liver effects, as well as neurodevelopmental and neurobehavioral effects of PCB 180. They also emphasize the potential value of metabolomics in characterizing toxic effects and in identifying sensitive biomarkers with potential future use in health risk assessment.

Lipidomic Response to Coffee Consumption.

Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry⁻mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p < 0.05 and q < 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p < 0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.

Metabolic Regulation of Pre- and Postnatal Growth.

Growth characteristics during periods of early developmental plasticity are linked with later health outcomes and with disease risks. Infant growth is modulated by genetic and exogenous factors including nutrition. We try to explore their underlying mechanisms using targeted metabolomic profiling of small molecules in biological samples using high-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) to quantify hundreds of molecules in small biosamples, e.g., 50 µL plasma. In the large German LISA birth cohort study, cord blood lysophosphatidylcholines and fatty acids were closely associated with infant birth weight, with a nonsignificant trend towards an association with infant weight gain and later BMI. Studies in infants randomized to different protein intakes in the European CHOP Study show conventional high protein intakes to markedly increase plasma-indispensable amino acids (AA), particularly branched-chain AA (BCAA), while exceeding the infant's capacity of BCAA breakdown, and an increase in the dispensable AA tyrosine previously associated with insulin resistance. In a path model analysis of the relationship of infant plasma AA, growth factors, and infant growth, AA were generally found to induce a stronger response of insulin than IGF-I although effects of individual AA were very different. We conclude that targeted improvement in nutrient supply in pregnancy and infancy may offer large opportunities for promoting desirable child growth patterns and long-term health.

Chiroptical spectroscopy and metabolomics for blood-based sensing of pancreatic cancer.

To enable the early diagnosis of pancreatic cancer, the search for and definition of reliable biomarkers remain a subject of great interest, with the specificity and sensitivity of the currently used biomarkers being below the required values. We tested a novel diagnostic approach for pancreatic cancer based on the specific molecular signature of blood plasma components. To acquire more detailed structural information, structure-sensitive chiroptical methods (electronic circular dichroism and Raman optical activity) were supplemented by conventional Raman and infrared spectroscopies. The obtained spectra were subsequently processed by linear discriminant analysis yielding high values of specificity and sensitivity. In addition, to monitor not only large biomolecules as potential biomarkers but also those of low molecular weight, we conducted an analysis of blood plasma samples by using metabolomics. The achieved results suggest a panel of promising biomarkers for a reliable detection of pancreatic cancer.

UPLC/Q-TOF-MS-based metabolomics study of the anti-osteoporosis effects of Achyranthes bidentata polysaccharides in ovariectomized rats.

Osteoporosis is a frequent disease among the elderly especially in postmenopausal women. Achyranthes bidentata is a traditional Chinese medicine used to strengthen bones. Here, A. bidentata polysaccharides (ABPs) were confirmed to have anti-osteoporosis effects. This study discovered biomarkers by comparing normal and osteoporosis rats and evaluated the effects of ABPs on osteoporosis based on the UPLC/Q-TOF-MS-based metabolomics analysis. We could then predict the underlying mechanisms from the perspective of metabolomics. Osteoporotic rats were treated with ABPs, and serum was then sampled for metabolic analysis. Glutarylcarnitine, lysoPC (18:1) and 9-cis-retinoic acid were identified as biomarkers. The ABPs could significantly increase these biomarkers, and this indicated that ABPs curing osteoporosis regulated lipid metabolism. The UPLC/Q-TOF-MS-based metabolomics analysis offered a potential strategy to evaluate the anti-osteoporosis effects of ABPs and to explain the relative mechanisms. Furthermore, the ABPs have good potential for treating osteoporosis.

The effect of coffee intake on lysophosphatidylcholines: A targeted metabolomic approach.

BACKGROUND & AIM: Lysophosphatidylcholines (lysoPC) are known to be a pathological component of oxidized-LDL, and several studies demonstrate its pro-inflammatory properties in vitro. Nevertheless, bioactive compounds found in coffee, such as phenolic acids might inhibit LDL oxidation. The relationship between coffee consumption and lysoPC has not been described previously in humans. The aim of the present study was to assess the association between coffee intake and plasma lysoPC levels in adults. METHODS: Data was from the "Health Survey of Sao Paulo (ISA-Capital)", a cross-sectional population-based survey in Sao Paulo, among 169 individuals aged 20 years or older. This population was categorized into three groups: non-coffee consumers (0 mL/day-G1), low coffee consumers (≤100 mL/day-G2), and high coffee consumers (>100 mL/day-G3). Usual coffee intake was estimated by two 24HR and one FFQ, using Multiple Source Method. Quantification of the metabolites was performed by mass spectrometry (FIA-MS/MS and HPLC-MS/MS) and 14 lysoPC species were identified. The association between coffee intake and lysoPC was analyzed by multiple linear regression adjusted for age, sex, household per capita income, smoking, physical activity, body mass index, total energy intake, use of drugs, vegetables and fruit consumption and caffeine intake. RESULTS: LysoPC levels were significantly lower in G3 than in G1, for the lysoPC a C16:1 (ß = -0.56; p = 0.014), lysoPC a C18:1 (ß = -2.57; p = 0.018), and lysoPC a C20:4 (ß = -1.14; p = 0.037). In opposition, the ratios of C16:0/C16:1 and C18:0/18:1 was higher in G3 (ß = 5.04; p = 0.025 and ß = 0.28; p = 0.003, respectively). CONCLUSION: LysoPC profile differed according to coffee intake, showing a possible beneficial health effect of this beverage on inflammatory and oxidative processes.

Blood pressure-lowering effect of Korean red ginseng associated with decreased circulating Lp-PLA2 activity and lysophosphatidylcholines and increased dihydrobiopterin level in prehypertensive subjects.

We evaluated the effects of red ginseng consumption on blood pressure (BP) and the fasting plasma metabolome. This randomized, double-blind, placebo-controlled study included nonobese, nondiabetic, prehypertensive subjects consuming 10 capsules daily containing 5 g red ginseng (n=31) or placebo (n=31). Fasting plasma metabolome profiles were obtained using ultra performance liquid chromatography-linear trap quadrupole Orbitrap MS. After 12 weeks, participants consuming red ginseng showed reductions of 6.5 and 5.0 mm Hg in systolic and diastolic BP, respectively. Compared with controls, those consuming red ginseng showed greater reductions in changed values of systolic BP, diastolic BP and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, after adjusting for baseline values. In addition, the red ginseng group showed a greater increase in dihydrobiopterin levels and greater decrease in palmitic amide and lysophosphatidylcholines (lysoPCs). The change in diastolic BP positively correlated with changes in lysoPCs and Lp-PLA2 activity. The BP-lowering effect of red ginseng is associated with decreased Lp-PLA2 and lysoPCs and increased dihydrobiopterin levels in prehypertensive subjects (ClinicalTrials.gov: NCT02326766).

UHPLC/Q-TOFMS-based metabolomics for the characterization of cold and hot properties of Chinese materia medica.

ETHNOPHARMACOLOGICAL RELEVANCE: The cold/hot property of Chinese materia medica (CMM) and the application of its corresponding knowledge in the diagnosis, differentiation and treatment of diseases have been considered to be the extremely important part of traditional Chinese medicine (TCM). As highly abstracted TCM theory, the cold/hot property of CMMs is still not fully understood and remains to be elucidated by systems biology approach. The cold and hot properties of CMM are mainly defined by the response of the body to a given CMM. Metabolomics is a promising systems biology method to profile entire endogenous metabolites and monitor their fluctuations related to an exogenous stimulus. Thus, a metabolomics approach was applied to characterize the cold and hot properties of CMMs. MATERIAL AND METHODS: Mice were intragastrically administered three selected cold property CMMs (i.e., Rheum palmatum L., radix et rhizoma; Coptis chinensis Franch, rhizome and Scutellaria baicalensis Georgi, radix) and three hot property CMMs (i.e., Cinnamomum cassia (L.) J. Presl, cortex; Zingiber officinale Roscoe, rhizoma and Evodia rutaecarpa (Juss.) Benth., fructus) once daily for one week. The comprehensive metabolome changes in the plasma of mice after treatment with cold or hot property CMMs were characterized by ultra-high performance liquid chromatography/time of flight mass spectrometry (UHPLC/Q-TOF-MS), and the potential biomarkers related to cold and hot properties of CMM were explored. RESULTS: Metabolites perturbation in plasma occurs after treatment with cold CMMs and hot CMMs in mice, and 15 and 16 differential biomarkers were identified to be associated with the cold and hot properties of CMMs, respectively. Among them, LPC (18:0), LPC (18:1), LPC (20:4) and LPC (20:5) showed decreased trends in the cold property CMM treated groups, but increased in the hot property CMM treated groups. CONCLUSIONS: There is a strong connection between the cold/hot property of CMMs and lysophosphatidylcholines metabolism. This study offers new insight into CMM properties and their clinical application.

The metabolic change of serum lysophosphatidylcholines involved in the lipid lowering effect of triterpenes from Alismatis rhizoma on high-fat diet induced hyperlipidemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Alismatis rhizoma (AR), a Traditional Chinese Medicine with lipid-regulating properties, is usually used to treat hyperlipidemia. Lysophosphatidylcholines (Lyso PCs) play a crucial role in lipid metabolism disorders. In this study, the triterpene fraction purified from boiling water extract of AR was evaluated for its lipid lowering activity using mice with high-fat diet (HFD) induced hyperlipidemia. The metabolic changes of individual Lyso PCs treated with the triterpene fraction were detected by ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometer (UHPLC-QTRAP-MS/MS). MATERIALS AND METHODS: HFD induced hyperlipidemia mice were administrated with triterpene and non-triterpene fractions at doses of 180, 360 and 720 mg/kg body weight/day for 4 weeks, respectively. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and atherogenic Index (AI) in mice serum were measured. The chemical components in the lipid-lowering fraction were characterized by ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). The changes of Lyso PC in the serum of mice treated with the lipid-lowering fraction were quantified by UHPLC-QTRAP-MS/MS. RESULTS: A total of 18 alisol derivatives were identified in the triterpene fraction. The hyperlipidemia mice treated with the triterpene fraction showed a significant decrease in serum TC, LDL-C and AI after continuous consumption of HFD for 4 weeks. The results also showed that 27 serum Lyso PCs in mice fed with HFD were down-regulated, and 19 were up-regulated. The abnormal serum level of Lyso PCs associated with hyperlipidemia was intervened by the alisol derivatives, with increase of unsaturated Lyso PCs and decrease of saturated ones. CONCLUSIONS: The study demonstrated for the first time that triterpenes from the AR extract can lower serum lipid level in HFD induced hyperlipidemia mice. These metabolism changes of Lyso PCs could further improve our understanding of the potential mechanism of lipid lowering effect of AR.

The triglyceride-lowering effect of supplementation with dual probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032: Reduction of fasting plasma lysophosphatidylcholines in nondiabetic and hypertriglyceridemic subjects.

BACKGROUND AND AIMS: This study evaluated the triglyceride (TG)-lowering effects of consuming dual probiotic strains of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on the fasting plasma metabolome. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled study was conducted on 92 participants with hypertriglyceridemia but without diabetes. Over a 12-week testing period, the probiotic group consumed 2 g of powder containing 5 × 10(9) colony-forming units (cfu) of L. curvatus HY7601 and 5 × 10(9) cfu of L. plantarum KY1032 each day, whereas the placebo group consumed the same product without probiotics. Fasting plasma metabolomes were profiled using UPLC-LTQ-Orbitrap MS. After 12 weeks of treatment, the probiotic group displayed a 20% reduction (p = 0.001) in serum TGs and 25% increases (p=0.001) in apolipoprotein A-V (apoA-V). At the 12-week follow-up assessment, the following 11 plasma metabolites were significantly reduced in the probiotic group than the placebo group: palmitoleamide, palmitic amide, oleamide, and lysophosphatidyl choline (lysoPC) containing C14:0, C16:1, C16:0, C17:0, C18:3, C18:2, C18:1, and C20:3. In the probiotic group, changes (▵) in TG were negatively correlated with ▵ apoA-V, which was positively correlated with ▵ FFA. In addition, ▵ FFA was strongly and positively correlated with ▵ lysoPCs in the probiotic group but not the placebo group. CONCLUSIONS: The triglyceride-lowering effects of probiotic supplementation, partly through elevated apoA-V, in borderline to moderate hypertriglyceridemic subjects showed reductions in plasma metabolites, fatty acid primary amides and lysoPCs (NCT02215694; http://www.clinicaltrials.gov). Clinical trials: NCT02215694; http://www.clinicaltrials.gov.

A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome.

The major pathway by which the brain obtains essential omega-3 fatty acids from the circulation is through a sodium-dependent lysophosphatidylcholine (LPC) transporter (MFSD2A), expressed in the endothelium of the blood-brain barrier. Here we show that a homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. We show that the p.Ser339Leu alteration does not affect protein or cell surface expression but rather significantly reduces, although not completely abolishes, transporter activity. Notably, affected individuals displayed significantly increased plasma concentrations of LPCs containing mono- and polyunsaturated fatty acyl chains, indicative of reduced brain uptake, confirming the specificity of MFSD2A for LPCs having mono- and polyunsaturated fatty acyl chains. Together, these findings indicate an essential role for LPCs in human brain development and function and provide the first description of disease associated with aberrant brain LPC transport in humans.