Effect of Baoyuan Jiedu Decoction on Interfering Serum Lipids and White Adipose Tissue Browning of Cancer Cachexia Mice / 浙江中医药大学学报

[Objective]To investigate the effect of Baoyuan Jiedu Decoction(BJD)on serum lipids and white adipose tissue browning in cancer cachexia mice.[Methods]The specific pathogen free C57BL/6 mice were divided into normal group,model group,BJD group and megestrol acetate(MA)group.After 21 days of intervention,the changes of body weight,food intake,water consumption and tumor volume of the mice were observed,multidimensional mass spectrometry-based shotgun lipidomics(MDMS-SL)was used to determine the content of serum lipid of mice,white adipose tissue morphology and lipid droplet area were detected by hematoxylin-eosin(HE)staining,the expressions of white adipose tissue browning related genes were detected by Real-time quantitative polymerase chain reaction(Real-time PCR);and the protein expression of uncoupling protein 1(UCP1)was detected by Western blot and immunohistochemistry(IHC)staining.[Results]Compared with model group,the mice in BJD group were generally in good condition,and their food intake,water consumption and weight were increased significantly(P＜0.05),and the volumes of tumors were significantly suppressed(P＜0.05).Compared with normal group,there were 61 kinds of abnormal lipids in the serum of model group,while 30 kinds of lipids were influenced by BJD treatment(P＜0.05).Compared with model group,BJD alleviated the mass loss and lipid droplets(P＜0.05),inhibited the mRNA expression of UCP1,Cidea,Prdm16(P＜0.05)and the protein expression of UCP1(P＜0.05)in epididymal white adipose tissue(eWAT)and inguinal white adipose tissue(iWAT)of cancer cachexia mice.[Conclusion]BJD can inhibit weight loss,relieve the disorder of serum lipid,and inhibit the white adipose tissue browning of iWAT and eWAT of cancer cachexia mice.

Clinical features and serum lipidomic profile of patients with nonalcoholic fatty liver disease and healthy individuals in the overweight population / 临床肝胆病杂志

objectiveTo investigate the differences in clinical indices and lipid metabolism between the patients with nonalcoholic fatty liver disease （NAFLD） and healthy individuals in the overweight population. MethodsIn this study， body mass index （BMI）>23 kg/m2 was defined as overweight. A total of 62 overweight patients with NAFLD who were admitted to Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to April 2021 were enrolled as overweight NAFLD group， and 50 overweight individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical information and blood biochemical parameters were recorded for all subjects. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze serum lipidomic profile， and principal component analysis and orthogonal partial least squares-discriminant analysis were used to perform the multivariate statistical analysis of lipidomic data. The chi-square test was used for comparison of categorical data between two groups， and the independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups. ResultsThe overweight NAFLD group had a significantly higher BMI than the overweight control group （Z=-2.365， P=0.018）. As for serological markers， compared with the overweight control group， the overweight NAFLD group had significantly higher levels of red blood cells， hemoglobin， hematocrit， uric acid， total protein， globulin， alkaline phosphatase， gamma-glutamyl transpeptidase， alanine aminotransferase， aspartate aminotransferase， cholinesterase， low-density lipoprotein， total cholesterol， triglyceride， apolipoprotein B， and blood glucose （all P<0.05）. The lipidomic analysis showed that there was a significant difference in lipid metabolism between the two groups， and a total of 493 differentially expressed lipids were identified （VIP value>1， P<0.05）， among which 143 lipids were significantly upregulated and 350 lipids were significantly downregulated in the overweight NAFLD group. The mean total fatty acid content in the overweight NAFLD group was 3.6 times that in the overweight control group. Compared with the overweight control group， the overweight NAFLD group had a significant reduction in the content of triglyceride with>3 unsaturated bonds （P<0.001） and a significant increase in the content of triglyceride with ≤3 unsaturated bonds （P<0.001）. ConclusionCompared with healthy overweight individuals， overweight NAFLD patients tend to have significant abnormalities in some biochemical parameters and lipid metabolites， with significant increases in the content of fatty acid in blood and the types of saturated fat chains in triglycerides.

Hepatic lipidomics study in chronic cadmium-exposed mice / 局解手术学杂志

Objective To study the change of lipidomics in chronic cadmium-exposed mice,thereby screening out lipid subclasses,lipid molecules and enriched metabolic pathways with significant differences.Methods Twelve SPF male C57BL/6J mice(8 weeks old)were randomly divided into the control group(normal water feeding)and the experimental group[cadmium water(0.6 mg/L of CdCl2)feeding],with 6 mice in each group.Mice were sacrificed after 6 months of cadmium exposure,and fresh liver tissues were collected immediately.Lipid oil red O staining and lipidomics analysis were performed on liver tissue.Results Compared with the control group,the liver tissue of mice in the experimental group did not appear red after lipid oil red O staining.Seventeen lipid subclasses with significant differences and 144 lipid molecules with significant differences were screened out by lipidomics.These lipid molecules with significant differences were enriched in glycerophospholipid metabolism,linoleic acid metabolism,alpha-linolenic acid metabolism,glycosylphosphati-dylinositol biosynthesis,glycerolipid metabolism and arachidonic acid metabolism by KEGG.Conclusion This study reveals that chronic cadmium exposure can induce the disorder of lipid subclasses and lipid metabolites in the liver of mice,which provides a basis for understanding the non-alcoholic fatty liver disease caused by chronic cadmium exposure.

Study on lipidomics of CD4+T cells in mice with diabetic kidney disease / 中国免疫学杂志

Objective:To investigate the lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.

The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis

Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

Metabolomics analysis of serum lipids in patients with acne vulgaris / 中国热带医学

@#Abstract: Objective To analyze and compare the differences in serum lipid metabolomics between patients with moderate to severe acne and healthy controls to understand the characteristics of serum lipid metabolism in acne patients. Methods Serum samples were collected from 30 patients with moderate to severe acne and 30 healthy controls matched for age, gender and body mass index in the Department of Dermatology, the Affiliated Hospital of Southwest Medical University from May 2019 to Apr. 2020. Serum lipid metabolomics was analyzed by liquid chromatography-tandem mass spectrometry. Partial least squares discriminant analysis (PLS-DA) was used for multivariate statistical analysis of differentially expressed lipid metabolites. The metabolic pathways with significant differences between the two groups were screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Using Mann-Whitney U test to calculate differential metabolites. Spearman correlation analysis was used to analyze the correlation between serum PC (18: 2e/20: 2) concentration and acne severity. Results The PLS-DA results showed that the composition of serum lipid metabolites in acne patients was significantly separated from that in healthy controls. Of the top 30 lipid metabolites with the most significant differences, four kinds of triglycerides (TG), two kinds of diglycerides (DG), six kinds of phosphatidylcholine (PC), one kind of MePC, two kinds of sphingomyelin (SM), two kinds of phosphatidylinositol (PI), two kinds of ceramide (monohexosyl ceramide, Hex1Cer;dihexosyl ceramide, Hex2Cer), two cardiolipin (CL) were found to be increased in the acne group (P<0.05). The levels of one kind of DG, two kinds of lysophosphatidyl ethanolamines (LPE), one kind of dimethylphosphatidyl ethanolamine (dMePE), one kind of bismethyl phosphatidic acid (BisMePA), three kinds of phosphatidyl ethanolamine (PE) and one kind of ceramide were found to be decreased in the acne group (P<0.05), and most of them belonged to phospholipid metabolites. Spearman correlation analysis showed that serum PC (18:2e/20:2) concentration was positively correlated with acne severity (r=0.456, P=0.004). KEGG enrichment function analysis revealed that the differential lipid metabolites were primarily enriched in metabolic pathways such as sphingolipid signaling pathway, cholesterol metabolism, insulin resistance, glycerophospholipid metabolism, among which the sphingolipid signaling pathway may play an important role. Conclusion There are significant differences in serum lipid metabolism between acne patients and healthy controls. Lipid metabolism disorders may be related to the pathogenesis of acne, but it’s molecular mechanism still needs further experimental exploration.

Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics / 中国中药杂志

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid β-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid β-oxidation, thereby improving rat obesity and dyslipidemia.

Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris / 中国实验方剂学杂志

ObjectiveThrough the targeted lipidomics， we explored the intervention mechanism of Kaixuan Bushen method on psoriasis vulgaris （PV） from the perspective of lipid metabolism， providing reference for the diagnosis and treatment of PV. MethodTwenty-six patients with PV admitting the outpatient clinic of the Department of Dermatology， Guang'anmen Hospital， China Academy of Chinese Medical Sciences from September 2019 to November 2020 were selected as the research object （observation group）， and 26 sex- and age-matched healthy volunteers in the same period were recruited as control group. Venous blood was collected for lipid index and targeted lipidomics detection in the control and observation groups at inclusion. After 12 weeks of continuous treatment of Kaixuan Bushen method， the psoriasis area and severity index （PASI） was measured and compared before and after treatment to assess the clinical efficacy， while venous blood was collected again in the observation group to compare the blood lipid level and lipid metabolism of patients before and after treatment. Targeted lipidomics analysis was performed by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS） on an ACQUITY UPLC BEH C8 column （2.1 mm×100 mm， 1.7 μm） with mobile phase of 5 mmol∙L-1 ammonium formate in acetonitrile-water （6∶4， A）-5 mmol∙L-1 ammonium formate in acetonitrile-isopropanol （1∶9， B） for gradient elution and flow rate of 0.26 mL∙min-1. Conditions of MS were electrospray ionization （ESI）， positive and negative ion modes， and scanning range of m/z 50-1 200. Then principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA） models were developed to screen differential metabolites， and the differential metabolites were identified and the pathways were enriched. ResultAfter 12 weeks of treatment with Kaixuan Bushen method， PASI score decreased by more than 50% in a total of 22 out of 26 patients with PV， suggesting the total effective rate was 84.62%. The serum triglyceride level of patients with PV was significantly higher than that of healthy individuals （P<0.05）， and the triglyceride level was significantly reduced after treatment （P<0.05）. Targeted lipidomics analysis screened a total of 43 potential biomarkers for PV， of which 42 were up-regulated and 1 was down-regulated， involving 7 signaling pathways such as linoleic acid metabolism， glycerophospholipid metabolism and unsaturated fatty acid biosynthesis. Moreover， there were 14 response makers for clinical efficacy of Kaixuan Bushen method on PV， of which 6 were up-regulated and 8 were down-regulated， involving five signaling pathways such as linoleic acid metabolism， glycerophospholipid metabolism and sphingolipids metabolism. In a comparison between healthy individuals and patients with PV and PV before and after treatment， the common differential metabolites were screened as phosphatidylcholine （PC） 38∶0 and ceramide （Cer） 42∶1， and the common pathways were linoleic acid and glycerophospholipid metabolic pathways. ConclusionThe disorder of lipid metabolism in PV are largely due to abnormal sphingolipid， glycerophospholipid and linoleic acid metabolic pathways， of which Kaixuan Bushen method can regulate the glycerophospholipid and linoleic acid metabolism， thereby improving psoriatic lesions.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice / 中西医结合学报

OBJECTIVE@#Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.@*METHODS@#To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity.@*RESULTS@#Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.@*CONCLUSION@#Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

The Effects of Rhubarb on Reproduction and Embryonic Development of Pregnant Rats Based on Amniotic Fluid Lipomics / 世界科学技术-中医药现代化

Objective To observe the metabolomic changes of amniotic fluid in control group and administration group,and to explore the toxicity of aqueous extract of rhubarb on reproduction and embryonic development of pregnant rats.Methods Pregnant rats in teratogenic sensitive period were given rhubarb aqueous extract by gavage for 10 days.The toxicity of rhubarb to maternal rats and the abnormal conditions of dead fetus and absorbed fetus were observed.The amniotic fluid samples were detected by liquid chromatography-mass spectrometry(LC-MS),the amniotic fluid metabolic profiles were compared by principal component analysis(PCA)and partial least squares(OPLS-DA),and the differential lipids were analyzed by metaboanalyst 5.0.Results Rhubarb administration in the teratogenic sensitive period can significantly reduce the number of live fetuses,and lead to adverse phenomena such as absorption of fetuses and premature death of fetuses.The preliminary results of lipomics showed that rhubarb could cause the metabolic disorder of amniotic fluid in pregnant rats,and there were metabolic abnormalities in lipids in amniotic fluid such as PI,PC and LPC.Conclusion Under the equivalent dose of the maximum dose recommended by the clinic,the aqueous extract of rhubarb has certain reproductive and embryonic toxicity to rats;Rhubarb may affect the normal development of rat embryos by causing the disorder of lipid metabolism in amniotic fluid.

Lipid-lowering effect of drug pair Scutellariae Radix-Coptidis Rhizoma based on lipomics / 中国中药杂志

This study investigated the mechanism of action of Scutellariae Radix-Coptidis Rhizoma(SR-CR) in intervening in non-alcoholic fatty liver disease(NAFLD) in rats based on lipidomics. Thirty-six SD rats were divided into a control group, a model group, SR-CR groups of different doses, and a simvastatin group, with six rats in each group. Rats in the control group were fed on a normal diet, while those in the remaining groups were fed on a high-lipid diet. After four weeks of feeding, drug treatment was carried out and rats were sacrificed after 12 weeks. Serum liver function and lipid indexes were detected using kits, and the pathomorphology of liver tissues was evaluated by hematoxylin-eosin(HE) staining and oil red O staining. Changes in lipid levels in rats were detected using the LC-MS technique. Differential lipid metabolites were screened by multivariate statistical analysis, and lipid metabolic pathways were plotted. The changes in lipid-related protein levels were further verified by Western blot. The results showed that compared with the control group, the model group showed increased levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.01), and decreased levels of γ-glutamyl transferase(γ-GT) and high-density lipoprotein cholesterol(HDL-c)(P<0.01), which were significantly recovered by the intervention of SR-CR. HE staining and oil red O staining showed that different doses of SR-CR could reverse the steatosis in the rat liver in a dose-dependent manner. After lipidomics analysis, there were significant differences in lipid metabolism between the model group and the control group, with 54 lipids significantly altered, mainly including glycerolipids, phosphatidylcholine, and sphingolipids. After administration, 44 differential lipids tended to normal levels, which indicated that SR-CR groups of different doses significantly improved the lipid metabolism level in NAFLD rats. Western blot showed that SR-CR significantly decreased TG-synthesis enzyme 1(DGAT1), recombinant lipin 1(LPIN1), fatty acid synthase(FASN), acetyl-CoA carboxylase 1(ACC1), and increased the phosphorylation level of ACC1. These changes significantly decreased the synthesis of TG and increased the rate of its decomposition, which enhanced the level of lipid metabolism in the body and finally achieved the lipid-lowering effect. SR-CR can improve NAFLD by inhibiting the synthesis of fatty acids and TG.

Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics,network pharmacology and pharmacokinetics / 药物分析学报

Nonalcoholic fatty liver disease(NAFLD)has developed into the most common chronic liver disease and can lead to liver cancer.Our laboratory previously developed a novel prescription for NAFLD,"Eight Zhes Decoction"(EZD),which has shown good curative effects in clinical practice.However,the pharmaco-dynamic material basis and mechanism have not yet been revealed.A strategy integrating lipidomics,network pharmacology and pharmacokinetics was used to reveal the active components and mecha-nisms of EZD against NAFLD.The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice.Furthermore,glycerophospholipid metabolism,arachidonic acid metabolism,glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA(PLA2G4A)and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid,12(S)-hydroxyeicosatetraenoic acid,leukotriene B4,prostaglandin E2,phosphatidylcholines(PCs)and triacylglycerols(TGs)as the main lipids were found to be involved in the treatment of NAFLD by EZD.Importantly,naringenin,artemetin,canadine,and bicuculline were iden-tified as the active ingredients of EZD against NAFLD;in particular,naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver.This research provides valuable data and theoretical support for the application of EZD against NAFLD.

Effects of passion fruit (Passiflora tenuifila Killip) intake on eutrophic and obese subjects: Lipidomic approach

Obesity and overweight result in metabolic changes that build up as risk factors for the development of the main non-communicable diseases. Among these alterations, dyslipidemia is an important risk factor for cardiovascular diseases (CDV) and is expressed in elevated plasma levels of triacylglycerols, cholesterol, and low-density-lipoprotein (LDL, VLDL) and decreased plasma levels of high-density lipoprotein (HDL). Passiflora tenuifila Killip is a native passion fruit species of the Brazilian Midwest region and is a good source of proanthocyanidins and dietary fibers. Proanthocyanidins are a class of phenolic compounds that are attributed with improving lipoprotein profile properties, translated as improved LDL/HDL ratio. Fibers are fermented by the gut microbiota and produce short-chain fatty acids (SCFA), also involved in the regulation of energetic metabolism.. A 30-consecutive-day-long intervention with lyophilized P. tenuifila flour was performed in eutrophic and obese subjects. Passion fruit ingestion increased fecal production of acetate, key SCFA in the modulation of lipid metabolism; reduced body fat percentage in all subjects; and reduced total cholesterol (TC) of subjects who presented basal CT > 130 mg/dL. After the intervention, plasma lipidomic analysis detected 44 statistically significant lipids, regardless of BMI. Considering the study population with altered TC, reduced levels of glycerophospholipids were observed, a lipid class studied for their involvement in CVD. The intake of P. tenuifila contributed to the improvement in cardiovascular risk markers and acts on lipid metabolism. These effects may be due to synergic action between the bioactive compounds in the fruit. Still, other studies are necessary to identify mechanisms related to the action of bioactives of P. tenuifila, which can be better directed by this lipidomic approach

A obesidade e o sobrepeso são preocupações resultam em alterações metabólicas que se acumulam como fatores de risco para o desenvolvimento a longo prazo das principais doenças crônicas não transmissíveis. Dentre essas alterações, a dislipidemia um importante fator de risco para doenças cardiovasculares (DCV), expressa em níveis plasmáticos elevados de triacilgliceróis, colesterol e das lipoproteínas de baixa densidade (VLDL, LDL), e níveis diminuídos da lipoproteína de alta densidade (HDL). Passiflora tenuifila Killip é uma espécie de maracujá nativa da região Centro-Oeste brasileira, e é uma boa fonte de proantocianidinas e fibras alimentares. As proantocianidinas são compostos fenólicos com reportados efeitos na melhora do perfil de lipoproteínas, traduzida como a relação LDL/HDL. As fibras são fermentadas pela microbiota intestinal e produzem ácidos graxos de cadeia curta (AGCC), metabólitos também envolvidos na regulação do metabolismo energético.. Assim, a lipidômica não-target é aplicada como ferramenta exploratória neste estudo: uma intervenção de 30 dias consecutivos de ingestão de P. tenuifila na forma de farinha liofilizada em indivíduos eutróficos e obesos. O consumo do maracujá promoveu aumento da produção fecal de acetato, AGCC importante na modulação do metabolismo lipídico; a redução do percentual de gordura corporal em todos os indivíduos; e redução do colesterol total (CT) para os indivíduos com CT > 130 mg/dL. A análise lipidômica do plasma detectou 44 lipídios estatisticamente relevantes, independentemente do IMC, após a intervenção. Considerando a população do estudo com CT alterado, foi observada uma redução de glicerofosfolipídios, classe de lipídios estudada pelo seu envolvimento em DCV. Assim, a ingestão de P. tenuifila contribui para a melhora nos marcadores de risco cardiovascular e atua no metabolismo lipídico. Estes efeitos podem ser decorrentes de sinergia entre os diversos compostos bioativos do fruto. Ainda, outros estudos são necessários para identificar mecanismos relacionados a ação dos bioativos da P. tenuifila e estes podem ser mais bem direcionados pela lipidômica

Screening of radiation sensitive lipids in rat plasma at early stage after total body irradiation with 60Co γ-rays / 中华放射医学与防护杂志

Objective:To explore the characteristics of lipid metabolism in rat plasma after total body irradiation(TBI) in order to provide scientific evidence of radiation biomarkers.Methods:For the non-targeted lipidomics study, 50 SD rats were divided into 6 groups and irradiated with 0, 1, 2, 3, 5 or 8 Gy 60Co γ-rays, respectively. For the targeted lipidomics study, 25 rats were divided into 5 groups and irradiated with 0, 0.5, 2.5, 4 or 6 Gy. Venous blood samples were collected and plasma were separated 4 h after TBI. Radiation-sensitive lipids were screened and their concentrations were determined. Receiver operating characteristic curve (ROC) and dose-response were analyzed. Results:A total of 15 radiation differential lipids were screened out based on non-targeted lipidomics study and 7 of them were identified as radiosensitive lipids by targeted lipidomics analysis. The ROC of radiosensitive lipids distinguished area under curve (AUC) of samples in 0 Gy group and > 0 Gy group, < 2 Gy group and ≥ 2 Gy group were all > 0.75. The AUC values were increased to 0.96 and 0.94 after the panel of radiation sensitive lipids ROC analysis. The concentrations of LysoPC(18: 2), LysoPC(22: 0), PC(18: 0/18: 2), PE(18: 2/16: 0) and PE(18: 2/18: 0) decreased with irradiation dose within 0-6 Gy.Conclusions:A total of 7 plasma radiosensitive lipids in rat plasma were identified 4 h after TBI, and the panel of them could be used for specific dose classification. Five of the lipids had good dose-response relationship.

Lipid markers and targets of coronary artery disease based on lipidomics / 药学学报

Coronary artery disease is the leading cause of death worldwide, the coronary artery stenosis or occlusion caused by atherosclerosis leads to myocardial ischemia, hypoxia, or necrosis, that is main histopathological features of coronary artery disease. Atherosclerosis relates closely to abnormal lipid regulation, chronic inflammation, and endothelial dysfunction. Cardiac enzymes and high, low-density lipoprotein are currently used to diagnose a variety of coronary artery diseases, but the evidence is inadequate. Thus, new cardioprotective therapies are required to explore sensitive molecular markers for the prediction of cardiovascular events. Lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Lipidomics is a newly emerged discipline that studies lipids on a large scale. Recent advancements in lipidomics on coronary artery disease have shown that certain lipids, such as ceramide, sphingosine, lysophosphatidic acid, oxidized lipids, and so on, are associated with the clinical classification and characteristics of coronary artery disease. In addition, recent studies of lipid profiles of the cardiac, fat, liver, and other tissue samples in animal models also have provided a novel viewpoint. Given the increasing application of lipidomics techniques for coronary artery disease, we provide a review of lipidomics technology, sensitive lipid markers, recent studies of therapeutic targets, and drug discovery for coronary artery disease.

Screening of lipid biomarkers in septic patients with different survival outcome / 中国综合临床

Objective:To screen lipid biomarker in sepsis patients with different survival outcome based on ultra high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS) technique.Methods:From September 2019 to April 2020, 30 septic patients admitted in Department of Intensive Care Unit and 30 cases of physical examination at the same time in Shanxi Bethune Hospital were studied. Lipid metabolite in serum were detected by UHPLC-MS/MS technique. According to the 28 day survival outcome of sepsis patients, they were divided into survival group (21 cases) and death group (9 cases). The baseline data of case group and control group, survival group and death group were compared respectively. Independent sample t-test and orthogonal partial least squares discriminant analysis (OPLS-DA) were further performed to identify lipid biomarkers related to sepsis survival outcome. Receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of differential lipids on the survival outcome of biomarker sepsis patients. Results:There were 32 lipid subclasses and 1 437 differential lipid molecules in the sepsis group compared with the control group. 196 differential lipid molecules in the sepsis survival group and the death group were screened according to the OPLS-DA model (variable weight of projection (VIP)>1), which were glycerophosphingolipids (129), sphingolipids (52), glycerides (14), and sterols (1).All the original data were statistically analyzed by univariate independent sample t-test. There were statistically significant differences in 15 lipid molecules between the two groups. Combined with VIP > 1 and P < 0.01, three lipid molecules were finally screened, which were sphingomyelin (SM) lipid molecules, SM (d30∶1), SM (d32∶2), SM (d32∶1). ROC curve analysis showed that the areas under curves of the above three lipid molecular were 0.915, 0.892, 0.898, respectively. The sensitivity was 77.27%, 95.45%,72.73%. The specificity was 100.0%, 87.5%,100.0%. Further Z-test showed that there was no significant difference in the area under the ROC curve ( Z(SM (d30∶1) and SM (d32∶1)) =0.36, P=0.722; Z(SM (d30∶1) and SM (d32∶2))=0.34, P=0.732; Z(SM (d32∶1) and SM (d32∶1))=0.07, P=0.942). Conclusions:Sphingomyelin may be involved in the formation of different clinical outcomes of sepsis, and has a good predictive effect on the survival outcome of sepsis.

Regulatory effect of Flos Abelmoschus manihot in mice with inflammatory bowel disease based on gut microbiota sequencing and untargeted lipidomics / 药学学报

In this study, the ameliorative effects of Flos Abelmoschus manihot on mice with chronic inflammatory bowel disease (IBD) were investigated and its effects on the structure of the intestinal flora as well as the lipid profile in feces of IBD mice were analyzed. All animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese medicine. A mouse model with chronic IBD induced by dextran sulfate sodium (DSS) was used to evaluate changes in body weight, disease activity index (DAI), colonic histopathological damage as well as gene expression levels of inflammatory factors in the colon. Fecal samples from mice in each group were collected and subjected to Illumina high-throughput sequencing to detect the abundance of intestinal flora; samples were analyzed by UHPLC-Q-Exactive® HF Quadrupole-Orbitrap® of untargeted lipidomics, which detects lipid content in feces. Administration of Flos Abelmoschus manihot could significantly restore the body weight and ameliorate colonic histopathological damage in IBD mice. Sequencing of the gut microbiota revealed that the species diversity and richness of the gut microbiota in IBD mice were decreased, with a significant increase in the abundance of Verrucomicrobia and a significant decrease in the abundance of Bacteroidetes; Flos Abelmoschus manihot significantly increased the richness and diversity of intestinal microbiota in IBD mice, increased the number of taxa species at each level, and restored the abundance of bacteria in the phylum Bacteroidetes. Analysis of fecal lipid profiles identified the most significant changes in sphingolipid and glycerophospholipid metabolic pathways in IBD mice, with Flos Abelmoschus manihot inhibiting ceramide and sphingomyelin synthesis in sphingolipid metabolism. In summary, Flos Abelmoschus manihot can effectively improve the disease condition of mice with chronic IBD, and it has the effect of regulating intestinal flora homeostasis and lipid metabolism, but the related mechanism between the two still needs to be deeply explored.

Nontargeted lipidomic analysis of sera from sepsis patients based on ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry / 中华危重病急救医学

Objective:To analyze the changes of serum lipidomics in patients with sepsis and healthy controls, search for the differences of lipid metabolites, and reveal the changes of lipidomics in the process of sepsis.Methods:A prospective observational study was conducted. From September 2019 to April 2020, morning blood samples of upper extremity superficial veins were collected from 30 patients with definite sepsis diagnosed in intensive care unit (ICU) of Shanxi Bethune Hospital and 30 age-matched healthy subjects during the same period. Serum lipid metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and the quality control samples were analyzed by base peak spectroscopy (BPC) and verified experimental repetition. Student t-test and fold change (FC) were used for screening significant differences in lipid metabolites and determining their expression changes. Principal component analysis (PCA) and orthogonal projectionto latent structure discriminant analysis (OPLS-DA) were used to determine the entire allocation of experimental groups apiece, access the quality of being near to the true value of model, and screen the differential lipid metabolites with variable importance of projection (VIP). Finally, Metabo Analyst platform database was used to analyze lipid molecular metabolic pathways. Results:BPC results showed that the experimental repeatability was good and the experimental data was reliable. The main parameter model interpretation rate of PCA model R 2X = 0.511, indicating that the model was reliable. The main parameter model interpretation rate of OPLS-DA model R 2Y = 0.954, Q 2 = 0.913, indicating that the model was stable and reliable. With FC > 2.0 or FC < 0.5, P < 0.05, a total of 72 differential lipid metabolites were obtained based on VIP > 1. Based on Metabo Analyst 5.0, 24 distinguishable lipid metabolites were identified including 8 phosphatidylethanolamine (PE), 7 lysophosphatidylcholine (LPC), 6 phosphatidylcholine (PC), 2 lysophosphatidylethanolamine (LPE) and 1 phosphatidylserine (PS). Compared with healthy volunteers, the lipid molecules expression proved down-regulated in most sepsis patients, including PC, LPC, LPE, and some PE, while some PE and PS were up-regulated, which was mainly related to the PE (18∶0p/20∶4), PC (16∶0/16∶0) and LPC (18∶1) metabolic pathways in glycerophospholipids. Conclusions:There are significant differences in lipid metabolites between the sera of sepsis patients and healthy volunteers. PE (18∶0p/20∶4), PC (16∶0/16∶0) and LPC (18∶1) may be new targets for sepsis prediction and intervention.

Caenorhabditis elegans deep lipidome profiling by using integrative mass spectrometry acquisitions reveals significantly altered lipid networks / 药物分析学报

Lipidomics coverage improvement is essential for functional lipid and pathway construction.A powerful approach to discovering organism lipidome is to combine various data acquisitions,such as full scan mass spectrometry(full MS),data-dependent acquisition(DDA),and data-independent acquisition(DIA).Caenorhabditis elegans(C.elegans)is a useful model for discovering toxic-induced metabolism,high-throughput drug screening,and a variety of human disease pathways.To determine the lipidome of C.elegans and investigate lipid disruption from the molecular level to the system biology level,we used integrative data acquisition.The methyl-tert-butyl ether method was used to extract L4 stage C.elegans after exposure to triclosan(TCS),perfluorooctanoic acid,and nanopolystyrene(nPS).Full MS,DDA,and DIA integrations were performed to comprehensively profile the C.elegans lipidome by Q-Exactive Plus MS.All annotated lipids were then analyzed using lipid ontology and pathway analysis.We annotated up to 940 lipids from 20 lipid classes involved in various functions and pathways.The biological in-vestigations revealed that when C.elegans were exposed to nPS,lipid droplets were disrupted,whereas plasma membrane-functionalized lipids were likely to be changed in the TCS treatment group.The nPS treatment caused a significant disruption in lipid storage.Triacylglycerol,glycerophospholipid,and ether class lipids were those primarily hindered by toxicants.Finally,toxicant exposure frequently involved numerous lipid-related pathways,including the phosphoinositide 3-kinase/protein kinase B pathway.In conclusion,an integrative data acquisition strategy was used to characterize the C elegans lipidome,providing valuable biological insights into hypothesis generation and validation.

Lipidomics reveals carnitine palrnitoyltransferase 1C protects cancer cells from lipotoxicity and senescence / 药物分析学报

Lipotoxicity,caused by intracellular lipid accumulation,accelerates the degenerative process of cellular senescence,which has implications in cancer development and therapy.Previously,camitine palmi-toyltransferase 1C (CPT1C),a mitochondrial enzyme that catalyzes carnitinylation of fatty acids,was found to be a critical regulator of cancer cell senescence.However,whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown.An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231,HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C.Cellular lipotoxicity was further confirmed by lipotoxicity assays.Significant changes were found in the lipidome of CPT1 C-depleted cells,including major alterations in fatty acid,diacylglycerol,triacylglycerol,oxidative lipids,cardiolipin,phosphatidylglycerol,phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin.This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialde-hyde and reactive oxygen species,signatures of lipid peroxidation and oxidative stress.Reduction of ATP synthesis,loss of mitochondrial transmembrane potential and down-regulation of expression of mito-chondriogenesis gene mRNAs indicated mitochondrial dysfunction induced by lipotoxicity,which could further result in cellular senescence.Taken together,this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence,suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.