Lipid Profile Metabolism Research Articles

Orange juice intake by obese and insulin-resistant subjects lowers specific plasma triglycerides: A randomized clinical trial.

Dyslipidaemia is usually common in obesity, insulin resistance, and type 2 diabetes mellitus. Clinical trials suggest that orange juice may have a positive impact on lipid metabolism and blood lipid profiles; however conflicting results have been reported. Here, we applied a combined untargeted/targeted lipidomic analysis of plasma to examine the impact of orange (Citrus sinensis) juice intake on the lipidome profile of obese and insulin-resistant subjects. Twenty-five participants, both sexes, aged 40-60 years, with obesity and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) index >2.71) ingested 400mL of orange juice 'Pera' (C.sinensis) for 15d. Cardiometabolic biomarkers, anthropometric parameters, blood pressure, and plasma lipidomic analysis results were assessed at the beginning and end of the intervention. After the 15-d intervention, a significant decrease was observed in the diastolic blood pressure and blood lipid profile. Among plasma lipidomes, 316 lipid molecules were identified, with the triglycerides (TGs) subclass being the most abundant (n=106). Plasma lipidome profiling revealed a major signature of the intervention; with concentrations of 37TG species decreasing after intervention. Qualitatively, oleic and linoleic acids were among the most prevalent fatty acids linked to the altered TG species, representing 50% of TG chains. Modulated TG species were positively correlated with total TG and very low-density lipoprotein levels, as well as systolic and diastolic blood pressure. A strong inter-individual trend was observed, wherein, compared with less responsive subjects, the high responsive subjects displayed the highest decrease in the concentrations of altered TG species, as as well as systolic blood pressure (decrease of 10.3±6.8mmHg) and body weight (decrease of 0.67±0.71kg). These findings suggest that orange juice has a positive impact on lipid metabolism, mainly regarding the composition of TG-specific fatty acid chains and cholesterol esters, protecting against insulin resistance. Furthermore, lipidomics may help clarify alterations at the molecular level after an intervention, contributing to improve the evaluation of the link between dyslipidaemia, insulin resistance, and nutrition.

Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia

BackgroundBerberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology.MethodsHLP hamster model was induced by high-fat diet. Hematoxylin—eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology.ResultsThe results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP.ConclusionsIn summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

The mediating role of maternal metabolites between lipids and adverse pregnancy outcomes of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and the demographics of pregnant women have changed in recent decades. GDM is a metabolic disease with short- and long-term adverse effects on both pregnant women and newborns. The metabolic changes and corresponding risk factors should be of great significance in understanding the pathological mechanism of GDM and reducing the incidence of adverse pregnancy outcomes in patients with GDM. The well-known GDM-associated lipids used in clinical tests, such as triglyceride (TG), are thought to play a major role in metabolic changes during GDM, which have a potential causal relationship with abnormal pregnancy outcomes of GDM. Therefore, this study analyzed the relationship between clinical lipid indicators, metabolic profiles, and abnormal pregnancy outcomes in GDM through mediation analysis. By constructing a metabolic atlas of 399 samples from GDM patients in different trimesters, we efficiently detected the key metabolites of adverse pregnancy outcomes and their mediating roles in bridging abnormal lipids and adverse pregnancy outcomes in patients with GDM. Our study confirmed that TG and total cholesterol were independent risk factors for adverse pregnancy outcomes in patients with GDM. Several key metabolites as mediators (e.g., gamma-linolenic acid, heptadecanoic acid, oleic acid, palmitic acid, and palmitoleic acid) have been identified as potential biomarkers for adverse pregnancy outcomes in patients with GDM. These metabolites mainly participate in the biosynthesis of unsaturated fatty acids, which may shed new light on the pathology of GDM and provide insights for further exploration of the molecular mechanisms underlying adverse pregnancy outcomes.

Abstract P3073: Altered Mitochondrial Mg 2+ Homeostasis In Liver Links Lipid Metabolism, Inflammation And Atherogenesis

Although evidences show the role of Mg 2+ in lipid metabolism and atherosclerosis, the molecular mechanism by which loss of Mg 2+ homeostasis promotes cardiovascular disease (CVD) is not known. Mg 2+ homeostasis is regulated by mitochondria and Mrs2 is the only known molecular machinery associated with mitochondrial Mg 2+ influx. To begin elucidating the importance of Mg 2+ homeostasis in lipid metabolism and CVD we made liver-specific Mrs2 KO mouse (Mrs2 Δhep ). Liver being the central hub of lipid metabolism, we asked whether loss of Mrs2 alters lipid metabolism and lipoprotein profile. Our results show increased accumulation of hepatic triacylglycerol (TG) and cholesterol in Mrs2 Δhep . Consistent with increased TG/cholesterol, plasma cholesterol and oxidized low density lipoprotein (ox-LDL) levels significantly differed between control and KO. Because ox-LDL contribute to atherosclerosis, we hypothesized altered hepatic lipid metabolism to induce inflammation, immune imbalance and accelerate lesions through modified atherogenic lipoprotein and cytokine profile. Quantification of plasma cytokines and chemokines were performed using the proteome profiler. Because T cells are critical drivers and modifiers of atherosclerosis, we quantified the lymphocyte and monocyte subsets by flow cytometry. Because T regulatory cells have anti-antherogenic roles, we studied the effect of ox-LDL on Tregs. Our results show increased and decreased levels of inflammatory and anti-inflammatory cytokines respectively in Mrs2 Δhep . In Mrs2 Δhep stimulation with ox-LDL showed an increased antigen specific proliferation of T-cells. We also observed increased and decreased population of Th17 and Tregs respectively. The decrease in Tregs population was attributed to increased apoptosis. In conclusion our observation suggests that high levels of ox-LDL in Mrs2 Δhep to induce inflammation and inflammatory cell expansion accompanied by apoptosis in Tregs. Our results conclude dysregulated Mg 2+ homeostasis to alter lipid metabolism and atherogenesis by inducing inflammation and compromised Tregs population. Our study will be the first of its kind to establish a triangular molecular link between Mg 2+ homeostasis, lipid metabolism, and atherogenesis.

Linking cellular lipid metabolism profiles to the outcomes of cholesterol-lowering therapy in a general population cohort study

Background and Aims : Alterations in cellular lipid metabolism are linked to differential treatment outcomes in familial hypercholesterolemia patients. However, whether similar effects exist in the general population is not known.

Lipid metabolism analysis for peripheral blood in patients with alcohol-induced and steroid-induced osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH), also known as vascular necrosis of the femoral head, is combined with lipid metabolism disorders in most patients. This study aims to explore the lipid metabolism profiles in different subtypes of ONFH. The subjects were divided into an alcohol-induced osteonecrosis of the femoral head (AONFH) group, a steroid-induced osteonecrosis of the femoral head (SONFH) group, and a normal control (NC) group (n=16, 29, and 32, respectively). Ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to detect the lipidomics analysis in the peripheral blood samples of subjects and identify the underlying biomarkers. The samples were preprocessed, the partial least squares discriminant analysis (PLS-DA) was adopted, and the variable importance for the projection (VIP) values were calculated to measure the expression pattern of each lipid metabolite and observe the influence and explanatory power of the expression pattern of each lipid metabolite on the classification and discrimination between the different groups. The lipid metabolites with fold change (FC)>2, P<0.05 and VIP>1 in the different groups were screened as differential lipids. Among them, the differential lipids co-existing in the AONFH group and the SONFH group were regarded as common differential lipids for ONFH, and the differential lipids that exist separately were regarded as specific differential lipids in the AONFH group or the SONFH group. Binary logistic regression was used to evaluate the diagnostic value of differential lipid metabolites on the basis of the receiver operator characteristic (ROC) curve analysis. Based on the disease stage information, the correlation between the differential lipids and the disease stage was analyzed in the AONFH group and the SONFH group. In this study, 1 358 lipid metabolites were detected in each plasma sample. Compared with the NC group, there were significant difference in the expression patterns of lipid metabolism profiles in the AONFH group and the SONFH group. A total of 62 and 64 differential lipid metabolites were screened in the AONFH and SONFH patients (FC>2, P<0.05, VIP>1) respectively, and these differential lipids were mainly up-regulated in the disease samples. Nine differential lipid metabolites were further identified, which were shared by the AONFH group and the SONFH group; the area under the curve (AUC) in 6 kinds of lipid components was greater than 0.7, including 1-myristoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, hypoxanthin, serotonin, PE (19:0/22:5), PE (19:0/22:5), and cholest-5-en-3-yl beta-D-glucopyranosiduronic acid. Fifty-three specific differential lipid metabolites were identified in the AONFH group, and 55 specific differential lipid metabolites were identified in the SONFH group. The AUC in 6 kinds of lipid components was greater than 0.9, including 1D-myo-Inositol 1,2-cyclic phosphate, L-pyroglutamic acid, DL-carnitine, 8-amino-7-oxononanoic acid, Clobetasol, and presqualene diphosphate. In the AONFH group, there were 9 differential lipid metabolites related to the disease stages, including LPG 18:1, serotonin, PC (22:4e/23:0), PC (19:2/18:5), hypoxanthin, PE (18:1/20:3), LPE 18:1, 1-stearoyl-2-arachidonoyl-sn-glycerol, and PE (16:0/18:1); with AONFH disease progresses from I/II stages to III/IV stages, the relative content of these 9 differential lipid metabolites was increased. In the SONFH group, 8 differential lipid metabolites were found to be related to the stage of the disease, including TM6076000, 4-(1,1-dimethylpropyl)phenol, D-617, asarone, phenylac-gln-OH, creatine, leu-pro, and 8-amino-7-oxononanoic acid; and with the SONFH progressed from stage I/II to stage III/IV, the content of these 8 differential lipid metabolites were gradually increased. This study analyzes the characteristics of the plasma lipid metabolism profile in the AONFH and SONFH patients, and which identifies the differential lipid metabolites related to disease diagnosis and evaluation. These results provide evidence for exploring lipid metabolism alterations and the mining of novel lipid biomarkers for the ONFH.

Adipocytokine profile in children with Kawasaki disease at a mean follow-up period of 5.5 years: A study from North India.

BACKGROUNDKawasaki disease (KD) is an acute self-limited vasculitis with a predilection for coronary arteries. Children with KD may have altered lipid metabolism and abnormal lipid profiles that may last for prolonged periods. However, there is a paucity of literature on the role of adipocytokines in KD. AIMTo estimate the levels of adipocytokines (adiponectin, leptin and resistin) during the convalescent phase of KD.METHODSTwenty children, who had KD at least three years earlier, were enrolled in this study. In addition, 20 healthy controls were also enrolled. Clinical and laboratory profiles of patients were obtained from hospital records. Serum adiponectin, leptin and resistin levels were estimated by enzyme-linked immunosorbent assay.RESULTSMean age of the patients in the study group was 10.15 ± 3 years and the male: female ratio was 1.5:1. Median serum resistin levels in patients with KD (27.77 ng/mL; [IQR: 18.66, 48.90]) were decreased compared to controls (21.20 ng/mL; [IQR: 14.80, 27.00]) (P = 0.04). Median serum leptin levels in cases and controls were 1.83 ng/mL; (IQR: 1.13, 3.80), and 1.10 ng/mL; (IQR: 0.41, 2.88), respectively (P = 0.09). Median serum adiponectin levels were similar in both cases (12.20 µg/mL; [IQR: 9.76, 17.97]) and controls (13.95 µg/mL; [IQR: 11.17, 22.58]); (P = 0.18). There was no significant difference in all 3 adipocytokines between children with (4/20) and without coronary artery abnormalities (16/20). CONCLUSIONSerum resistin levels were significantly elevated in patients with KD during the convalescent phase compared to controls. Serum leptin levels appeared to be higher in patients with KD, although the difference was not statistically significant. Adiponectin levels were similar in both cases and controls. Raised resistin and leptin levels may partially explain lipid perturbations observed during the convalescent phase of KD.

An Integrated Transcriptomics and Lipidomics Analysis Reveals That Ergosterol Is Required for Host Defense Against Bacterial Infection in Drosophila.

Animals adjust their lipid metabolism states in response to pathogens infection. However, the underlying molecular mechanisms for how lipid metabolism responds to infection remain to be elusive. In this study, we assessed the temporal changes of lipid metabolism profiles during infection by an integrated transcriptomics and lipidomics analysis. Ergosterol is identified to be required for proper host defense to pathogens. Notably, ergosterol level is increased in the hemolymph upon bacterial infection. We show that the increase of ergosterol level by food supplement or genetic depletion of Acsl, a long-chain fatty acid-CoA synthetase, promotes host survival against bacterial challenges. Together, our results suggest a critical role of lipid metabolism adaption in the process of host defense against invading pathogens.

Effect of L-carnitine on the Lipid Profile, Glycemic Control, Oxidative Stress, and Anthropometric Indices of Individuals with Type 2 Diabetes

Diabetes mellitus is one of the most prevalent metabolic diseases in existence. With more than 536.6 million cases having been diagnosed globally, its prevalence is reported to be 10.5% in 2021. In individuals with diabetes, plasma L-carnitine is low and metabolized abnormally. In this review, we aimed to assess whether L-carnitine supplementation is correlated with a reduction of the risk of cardiovascular diseases in individuals with diabetes by improving the compositions of lipid profiles, indicators of oxidative stress, glycemic control, and anthropometric indices. A literature search in major databases such as Web of Science, PubMed, Google Scholar, Scopus, and Scientific Information Database was conducted until November 2021. This was done in conjunction with a search in Elsevier and SpringerLink databases, resulting in the inclusion of relevant articles in this review. To construct the search strategy, “Carnitine” OR “glycine propionyl carnitine” OR “Acetylcarnitine” in combination with “Diabetes Mellitus” OR “Diabetes Complications” OR “Lipid Profile” and all of its components were used to search for and within the articles and databases. After screening, 10 articles published between 1998 and 2017 were identified. They evaluated the effect of L-carnitine on lipid profile metabolism, glycemic control, anthropometric indices, and oxidative stress markers in individuals with diabetes. In this systematic review, we concluded that L-carnitine had no notable effect on lipid profile as well as glycemic control and anthropometric indices. Therefore, using L-carnitine probably has no notable effect on metabolic status in individuals with diabetes. Meanwhile, some articles suggested that L-carnitine may have positive effects on some oxidative stress indicators.

Lipidomics characterization of the lipid metabolism profiles in a cystinuria rat model: Precalculus damage in the kidney of cystinuria

Cystinuria is a genetic disorder of cystine transport, including defective protein b0,+AT (encoded by SLC7A9), and/or rBAT (encoded by SLC3A1). Patients present hyperexcretion of cystine in the urine, recurrent cystine lithiasis, and progressive decline in kidney function. Moreover, heterodimer transport is defective. To date, little omics data are accessible regarding this metabolic disease caused by membrane proteins. Since membrane function is closely related to changes in the lipidome, we decided to explore the changes in kidney tissue of a self-established cystinuria rat model by performing lipidomic analysis by LC-MS/MS. Our results demonstrated that Slc7a9 deficiency changed the lipid profile of the renal cortex and induced vital modifications in the lipidome, including major alterations in ChE, LPA, and PA. Among those alterations, this lipidomic study highlights the lipid changes that participate in inflammatory responses during cystinuria. As a result, lipid research, perhaps has great potential, for it may lead to the identification of novel therapeutic targets for the prevention and treatment of cystinuria.

The Antioxidant Activity of Thymus serpyllum Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice.

Nowadays, there is an increasing interest in alternative therapies in the treatment of metabolic syndrome that combine efficacy and safety profiles. Therefore, this study aimed to evaluate the effect of an extract of Thymus serpyllum, containing rosmarinic acid, on high-fat diet (HFD)-induced obesity mice, highlighting the impact of its antioxidant activity on the inflammatory status and gut dysbiosis. The extract was administered daily (50, 100 and 150 mg/kg) in HFD-fed mice. The treatment reduced body weight gain, glucose and lipid metabolic profiles. Moreover, the extract ameliorated the inflammatory status, with the c-Jun N-terminal kinases (JUNK) pathway being involved, and showed a significant antioxidant effect by the reduction of radical scavenging activity and the mitigation of lipid peroxidation. Moreover, the extract was able to modulate the altered gut microbiota, restoring microbial richness and diversity, and augmenting the counts of short-chain fatty acid producing bacteria, which have been associated with the maintenance of gut permeability and weight regulation. In conclusion, the antioxidant activity of Thymus serpyllum extract displayed a positive impact on obesity and its metabolic alterations, also reducing systemic inflammation. These effects may be mediated by modulation of the gut microbiota.

Chilean pepper (Schinus polygamus) ameliorates the adverse effects of hyperglycaemia/dyslipidaemia in high fat diet/streptozotocin-induced type 2 diabetic rat model

Diabetes is a life-threatening metabolic disease marked by hyperglycaemia, endocrine system abnormalities, and aberrant lipid metabolic profiles. The study targeted to identify the phytochemical constituents of Schinus polygamus leaf extract (SPLE) and evaluate its ameliorative effects on the oxidative stress and metabolic abnormalities caused by high-fat diet (HFD) with low dose of streptozotocin (STZ) in male rats. The high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) analysis of SPLE revealed identification of fourteen compounds of phenolic nature, such as gallic acid, catechin, methyl gallate, pentagalloyl-O-hexoside and catechin-O-hexoside. The type-2 diabetic mellitus (T2DM) model was established by HFD and STZ (i.p; 30 mg/kg). The T2DM animals orally administrated two doses of SPLE (200 & 400 mg/kg b.w/day) or metformin (400 mg/kg/day, orally) for one month. The extract dose-dependently enhanced the body weight gain, BMI, hepatorenal toxicity markers, hyperglycaemia, homeostatic model assessment for insulin resistance (HOMA-IR), insulin level, lipid peroxidation and dyslipidaemia of diabetic rats. It also improved insulin sensitivity and antioxidant defense system. Moreover, it modulated the levels of proinflammatory adipokines (adiponectin & leptin). Further, it downregulated inducible pro-inflammatory genes (NF-ĸB & iNOS mRNA expression). The present study elicited antihyperlipidemic, antihyperglycemic, anti-insulin resistance, anti-inflammatory, antioxidant properties of S. polygamus. Thereby, it could be a new adjuvant candidate in the T2DM management.

Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat

BackgroundAcne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. Cryptotanshinone (CPT) is a potential drug for acne, but its mechanism of acne treatment has not been thoroughly studied on the microbiota. Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. PurposeThe action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. MethodsThe 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. Four key proteins of the glycolysis pathway were detected with the immunochemistry method. Antibacterial analysis was used to evaluate CPT treatment of acne. ResultsCPT significantly inhibited Staphylococcus epidermidis and Staphylococcus aureus. Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. Cer was mainly regulated by Staphylococcus and Corynebacterium, whereas TG and DG were mainly regulated by Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. The glycolysis pathway was significantly regulated by Staphylococcus on CPT treatment of acne. The energy metabolism, lipid metabolism, immune system, glycan biosynthesis, and metabolism could be reversed by CPT. ConclusionCPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms.

Effects of oral contraceptives plus orlistat in patients with polycystic ovary syndrome and overweight/obesity: A meta-analysis.

This meta-analysis was conducted to compare the effect and safety of oral contraceptive pills (OCP) plus orlistat with OCP alone in clinical, hormonal, and lipid metabolism outcomes in patients with polycystic ovary syndrome (PCOS) and overweight/obesity. Pubmed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and SinoMed were systematically reviewed. A random-effects or fixed-effects model was used to pool the estimate. Eight studies were included in this meta-analysis. Significant reductions in BMI, WHR, and waist circumference were observed in combination group as compared with OCP alone group. Regarding the hormonal outcome, T, SHBG, FAI, LH, DHEAS, FSH, and E2 levels were significantly improved in combination group compared with OCP alone group. However, the TT and FT did not change significantly between the two groups. Regarding the lipid metabolism outcomes, TC, LDL-C, and TG levels were reduced and HDL-C level was increased in the combination group. Regarding the insulin metabolism outcomes, FINS and HOMA-IR levels were reduced in combination group than in OCP group. The ovulation rate, pregnancy rate, and overall effective rate were significantly higher in combination group than in OCP alone group. Fewer complications were observed in the combination group than in OCP group, and the difference between them was significant. This combination treatment of OCP and orlistat was more effective than OCP alone in reducing the weight, hormonal, lipid, and insulin metabolism profiles, as well as improving the ovulation rate, pregnancy rate, and overall effective rate, as compared with OCP alone.

Targeted Lipidomics Reveal the Effect of Perchlorate on Lipid Profiles in Liver of High-Fat Diet Mice.

Perchlorate, commonly available in drinking water and food, acts on the iodine uptake by the thyroid affecting lipid metabolism. High-fat diets leading to various health problems continually raise public concern. In the present study, liver lipid metabolism profiles and metabolic pathways were investigated in C57BL/6J mice chronically exposed to perchlorate using targeted metabolomics. Mice were fed a high-fat diet and treated orally with perchlorate at 0.1 mg/kg bw (body weight), 1 mg/kg bw and 10 mg/kg bw daily for 12 weeks. Perchlorate induced disorders of lipid metabolism in vivo and hepatic lipid accumulation confirmed by serum biochemical parameters and histopathological examination. There were 34 kinds of lipid in liver detected by UHPLC-MS/MS and key metabolites were identified by multivariate statistical analysis evaluated with VIP > 1, p-value < 0.05, fold change > 1.2 or < 0.8. Perchlorate low, medium and high dose groups were identified with 11, 7 and 8 significantly altered lipid metabolites compared to the control group, respectively. The results of the metabolic pathway analysis revealed that the differential metabolites classified into different experimental groups contribute to the glycerophospholipid metabolic pathway. These findings provide insights into the effects of perchlorate on lipid metabolism during long-term exposure to high-fat diets and contribute to the evaluation of perchlorate liver toxic mechanisms and health effects.

119 Randel Lectureship: The Role of Maternal Nutrition in Developmental Programming Using a Sheep Model

Abstract Appropriate nutrition during gestation is critical for optimal fetal development and life-long health. Poor nutrition during gestation, defined as excess or restricted nutrition, can lead to altered growth and metabolic dysregulation in the offspring. Using a sheep model, we have demonstrated that both restricted- and over-feeding alter offspring growth, impair muscle growth, increase fat accumulation, alter circulating growth and metabolic hormones, and alter mRNA expression of genes involved in myogenesis, lipogenesis, inflammation, and glycogen metabolism. More importantly, these negative impacts of poor maternal nutrition persist through adulthood, and can be passed to subsequent generations. Using omics approaches, we have begun to elucidate the mechanisms by which maternal diet impacts developmental programming and contributes to these persistent effects. In offspring from restricted-fed mothers, fetal liver and muscle morphology demonstrated impaired growth and alterations in key metabolites in methionine, betaine, and bile salt pathways. In offspring from both restricted- and over-fed mothers, global metabolomics demonstrated altered lipid and protein metabolism profiles. These changes in metabolites likely contribute to maternal programming of offspring growth and metabolism including efficiency of energy utilization. In addition to changes in key genes involved in growth, lipid accretion, and protein synthesis, preliminary studies suggest these persistent effects may be due to changes epigenetic regulation in offspring. Using the sheep model of both restricted- and over-feeding we, and others, have demonstrated that the negative effects of poor maternal nutrition affect multiple key metabolic tissues during fetal development and that these changes persist into maturity. Therefore, the focus of our current studies is to determine the multigenerational impacts of poor maternal nutrition on offspring growth and health and elucidate the mechanisms that contribute to these persistent changes.

Black-Eyed Pea Diet Alleviates High-Density Lipoprotein Cholesterol In Menopausal Women; Randomized Clinical Trial Study

Introduction: Menopause is defined as the last menstruation cycle in women. Estrogen concentration in menopausal women was decreased and altered the lipid metabolism profiles. Menopausal women reportedly have a high risk of cardiovascular disease, arthritis, diabetes mellitus, and stroke. This study focused on the effect of the black-eyed pea diet on the lipid profiles in menopausal women.&#x0D; Material and Methods: A randomized clinical study was performed to analyzedd the effect of the black-eyed pea diet on lipid profiles. Fifty-four menopausal women were selected as respondents and classified into two groups, black-eyed pea diet and placebo. Black-eyed pea diet treatment was performed by consuming black-eyed powder containing 67.5 mg of isoflavones and were monitored in week – 0 and week – 12 after treatment. Lipid profile of black-eyed pea diet and placebo in 12 weeks monitoring showed no significant value. After 12 weeks of treatment, total cholesterol and triglyceride were higher than before treatment.&#x0D; Results: Interestingly, the black-eyed pea diet increased the HDL and lowered the LDL after 12 weeks of treatment.&#x0D; Conclusion: This study concluded that black-eyed pea improved lipid profile, especially in elevating HDL level and decreasing LDL level in 12 weeks consumption.

LPL, FNDC5 and PPAR\u03b3 gene polymorphisms related to body composition parameters and lipid metabolic profile in adolescents from Southern Italy

BackgroundPlasma lipid profile and anthropometric variables are known to be under strong genetic control and the identification of genetic variants associated with bioclinical parameters is of considerable public health importance. In this study, a young cohort of healthy individuals was genotyped for genes related to health and pathological conditions, to analyze the association of single nucleotide polymorphisms (SNPs) with different bioclinical parameters, adherence to the Mediterranean Diet (MD) and physical activity, studying the role of lifestyle and body composition parameters on biochemical metabolic profile.MethodsAssociation analysis of single variants in the genes of lipoprotein lipase (LPL), fibronectin type III domain containing protein 5 (FNDC5), and peroxisome proliferator-activated receptor-gamma (PPARγ) and haplotype analyses were performed.ResultsMultiple (n = 14) common variants in the three genes demonstrated a significant effect on plasma lipoprotein-lipid levels and/or on biochemical parameters in our sample. Specifically, SNPs were related to lipid metabolism (rs3866471, rs4922115, rs11570892, rs248, rs316, rs1059507, rs1801282) or glycemic profile (rs3208305) or anthropometric parameters (rs3480, rs726344, rs1570569) for a total of 26 significant associations (P < 0.01 and/or P < 0.05) and two haplotypes, for the first time, were strongly associated with lipid and body composition parameters. Interestingly, we identified twenty-four new variants not previously described in the literature and a novel significant association between rs80143795 and body composition.ConclusionsIn this study we confirm the association between these SNPs on lipid metabolism and body parameters also in a young cohort, indicating the important role of these genetic factors as determinants of health.

Impact of Mediterranean Diet Food Choices and Physical Activity on Serum Metabolic Profile in Healthy Adolescents: Findings from the DIMENU Project.

Adolescent nutrition and healthy dietary patterns, particularly the Mediterranean diet (MD), have been associated with improved health status and decreased risk of various chronic and metabolic diseases later in life. The aim of this study was to evaluate the impact of the Mediterranean food choices on lipid and glycemic metabolic profile in the total population and in adolescents grouped according to their physical activity (PA) levels at the time of recruitment (T0) and after six months from the administration of a personalized Mediterranean meal plan (T1). As part of the DIMENU study, 85 adolescents underwent measurements of lipid and glucose metabolic profile at T0 and T1. Using three positive items from KIDMED test related to the consumption of typical Mediterranean food (olive oil, fish, and nuts) and three negative items on dietary habits (going to fast-food, consuming biscuits, and candies), we categorized adolescents into six sets in which biochemical parameters were analyzed. In the total sample, significant reductions in serum total cholesterol, LDL, and glucose concentrations were observed for all the sets over the study period. Notably, active subjects, who had a better serum metabolic profile, showed significant improvements of glycemic control after 6 month follow up, while in sedentary adolescents and in those performing moderate PA significant reduction in glycemia, total cholesterol, and LDL was found in all sets. In conclusion, adopting the typical Mediterranean food choices led to a significant reduction in glucose and lipid profile in healthy adolescents, thus making the MD and PA a winning combination for health status.

Lipid metabolomic analysis in exosomes of osteonecrosis of the femoral head based on ultra performance liquid chromatography-tandem mass spectrometry

股骨头坏死(ONFH)是一种可导致股骨头塌陷进而需要接受全髋关节置换的疾病。外泌体作为一种细胞间交流的方式,在一系列生理和病理过程中起着至关重要的作用,已在疾病的诊断和治疗中发挥独特作用。该研究利用非靶向代谢组学方法,探讨股骨头坏死组织外泌体内的脂质代谢特征,阐释股骨头坏死时机体发生的脂质代谢变化。该研究采用超速离心的方法,对股骨头坏死组织的外泌体进行了分离富集,并使用动态光散射(DLS)、蛋白质免疫印迹和透射电子显微镜(TEM)3种方法鉴定外泌体。采用超高效液相色谱-串联质谱(UPLC-MS/MS)结合多变量统计分析识别股骨头坏死外泌体的脂质代谢谱。采用主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)对差异表达的外泌体脂质代谢物进行多变量统计分析。在外泌体中检测到18种明显改变的脂质代谢物,包括丙烯醇酯类、脂肪酸酯类、甘油酯类及其衍生物。通过代谢分析网站进行通路分析,从而确定受影响的代谢通路并进行可视化。代谢通路分析显示外泌体内的甘油磷脂代谢和鞘脂代谢改变最为明显,鞘脂和甘油磷脂之间的不平衡导致脂肪毒性损伤,这与常见代谢性疾病的病理生理学有关。同时,甘油磷脂与细胞增殖、分化和凋亡之间具有相关性,甘油磷脂比例的变化可以反映脂质代谢的紊乱。外泌体内的脂质代谢变化可能在一定程度上反映了ONFH疾病的代谢变化。ONFH外泌体脂质代谢组学分析可有助于探索坏死骨组织外泌体中的脂质代谢变化和受影响的脂质代谢通路。