Lipid Pattern Research Articles

Postprandial dyslipidemia after a standardized high-fat meal in BMI-matched healthy individuals, and in subjects with prediabetes or type 2 diabetes

A relationship between postprandial hyperlipidemia and glucose homeostasis/cardiovascular diseases has been suggested. We investigated postprandial plasma lipid patterns after a standardized high-fat meal and their association with glucose homeostasis and subclinical atherosclerosis. Using matching by BMI, 32 healthy individuals with normal glucose tolerance (NGT), 21 subjects with impaired glucose tolerance (IGT), and 20 subjects with drug-naïve type 2 diabetes (T2D) were enrolled. Plasma concentrations of triglycerides (TGs), apolipoprotein-B (ApoB), ApoB48, ApoB100, glucose, and insulin at baseline and 1, 2, 3, 4, 5, 6, and 8h after a standardized meal (1041.03kcal with 70.99g of fat) were measured. Body composition, abdominal visceral fat area, and resting energy expenditure (REE) were measured using dual energy X-ray absorptiometry, computed tomography, and indirect calorimetry, respectively. The intima-media thickness (IMT) of the carotid artery and the ankle-brachial index (ABI) were used to detect subclinical atherosclerosis. Baseline data and area under the curve (AUC) of plasma concentrations of TGs, ApoB, and ApoB48 in the IGT and T2D groups were higher than in the NGT group. The peak TG concentrations after the meal was observed at 5h in subjects with IGT and T2D, while healthy subjects showed the highest concentrations at 4h. In multivariable analysis, high abdominal visceral fat area and low HDL-cholesterol concentrations were independently associated with the AUCTG and AUCApoB after adjusting for confounders including baseline TG and the REE. High LDL-cholesterol and high HbA1c concentrations were also associated with the AUCApoB. Furthermore, high AUCTG and AUCApoB values were independent factors for an increased carotid IMT and a low ABI after adjusting for relevant variables. Abdominal visceral obesity and low HDL-cholesterol concentrations were associated with increased post load excursions of TGs and ApoB in this series. These elevated concentrations of TGs and ApoB were linked with subclinical atherosclerosis.

MP58-12 LESS MORTALITY AND LESS MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) UNDER LONG-TERM TESTOSTERONE THERAPY (TTh): 15-YEAR DATA FROM A PROSPECTIVE CONTROLLED REGISTRY STUDY

You have accessJournal of UrologyHealth Services Research: Quality Improvement & Patient Safety IV (MP58)1 Sep 2021MP58-12 LESS MORTALITY AND LESS MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) UNDER LONG-TERM TESTOSTERONE THERAPY (TTh): 15-YEAR DATA FROM A PROSPECTIVE CONTROLLED REGISTRY STUDY Ahmad Al-Qudimat, Mustafa Alwani, Raed M. Al-Zoubi, Khalid Al-Rumaihi, Raidh Talib, Karim Haider, and Farid Saad Ahmad Al-QudimatAhmad Al-Qudimat More articles by this author , Mustafa AlwaniMustafa Alwani More articles by this author , Raed M. Al-ZoubiRaed M. Al-Zoubi More articles by this author , Khalid Al-RumaihiKhalid Al-Rumaihi More articles by this author , Raidh TalibRaidh Talib More articles by this author , Karim HaiderKarim Haider More articles by this author , and Farid SaadFarid Saad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002088.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We have previously demonstrated improvements in cardiometabolic risk factors in hypogonadal men on long-term TTh. METHODS: Cumulative registry study to investigate long-term effectiveness and safety of 3-monthly TU to treat hypogonadism was established in 2004 in a urological setting. Of 805 hypogonadal men, 412 received parenteral TU 1000 mg/12 weeks (T-group) for up to 12 years. 393 men opted against TTh and served as controls (CTRL). 10-year data are reported. Confounders including age, BMI, smoking, alcohol, total and HDL cholesterol, systolic blood pressure and type 2 diabetes were assessed and considered in statistical modelling. RESULTS: Baseline age was 57.7±7.4 in the T-group and 63.7±4.8 years in CTRL (p <0.001). The absolute follow-up time comprised approximately 6.500 patient-years. The mean Framingham risk score at baseline was 15.5 in the T-group and 15.8 in CTRL (p <0.05). The mean 10-year risk was 22.7% in the T-group and 23.5% in CTRL (p=0.11). Mean and median observation time in the T-group was 8 years. There were 16 deaths (3.9%) but no myocardial infarctions or strokes. Mean observation time in CTRL was 8, median 9 years. There were 74 deaths (18.8%), 70 MIs (17.8%) and 59 strokes (15%). All classical cardiovascular risk factors including obesity, glycaemic control, lipid pattern, and C-reactive protein improved in the T-group and worsened in CTRL. The reduction of cardiovascular events by TTh after applying a linear mixed effect model was 24.7% and 15.5% after applying a random effect longitudinal model. CONCLUSIONS: In hypogonadal men, long-term (TTh) reduces cardiovascular events and mortality. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e992-e993 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmad Al-Qudimat More articles by this author Mustafa Alwani More articles by this author Raed M. Al-Zoubi More articles by this author Khalid Al-Rumaihi More articles by this author Raidh Talib More articles by this author Karim Haider More articles by this author Farid Saad More articles by this author Expand All Advertisement PDF downloadLoading ...

Increased Hypothalamic Anti-Inflammatory Mediators in Non-Diabetic Insulin Receptor Substrate 2-Deficient Mice.

Insulin receptor substrate (IRS) 2 is a key mediator of insulin signaling and IRS-2 knockout (IRS2−/−) mice are a preclinical model to study the development of diabetes, as they develop peripheral insulin resistance and beta-cell failure. The differential inflammatory profile and insulin signaling in the hypothalamus of non-diabetic (ND) and diabetic (D) IRS2−/− mice might be implicated in the onset of diabetes. Because the lipid profile is related to changes in inflammation and insulin sensitivity, we analyzed whether ND IRS2−/− mice presented a different hypothalamic fatty acid metabolism and lipid pattern than D IRS2−/− mice and the relationship with inflammation and markers of insulin sensitivity. ND IRS2−/− mice showed elevated hypothalamic anti-inflammatory cytokines, while D IRS2−/− mice displayed a proinflammatory profile. The increased activity of enzymes related to the pentose-phosphate route and lipid anabolism and elevated polyunsaturated fatty acid levels were found in the hypothalamus of ND IRS2−/− mice. Conversely, D IRS2−/− mice have no changes in fatty acid composition, but hypothalamic energy balance and markers related to anti-inflammatory and insulin-sensitizing properties were reduced. The data suggest that the concurrence of an anti-inflammatory profile, increased insulin sensitivity and polyunsaturated fatty acids content in the hypothalamus may slow down or delay the onset of diabetes.

EVALUATION OF C-RP AND LIPID PROFILE IN COPD AS A MARKER OF SYSTEMIC INFLAMMATION AND ATHEROGENIC LIPID PATTERN.

Chronic obstructive pulmonary disease (COPD), a progressive disease of the lungs characterized by persistent airflow limitation, is one of the main causes of morbidity and mortality worldwide. Epidemiological studies reported that COPD patients have various extrapulmonary comorbidities such as coronary heart disease (CHD), metabolic syndrome, and depression. Extrapulmonary comorbidities increase the risk of hospitalisation and mortality in COPD patients. An increasing number of COPD patients die from systemic comorbidities rather than respiratory failure. Purpose of present study was to measure serum C-reactive protein (C-RP) and lipid profile in COPD patient to establish its correlation as early predictor of risk factors CHD. Aim: To investigate the levels of serum C-RP,cholesterol (TCH), triglycerides (TG), low density lipoproteins (LDL), very low density lipoproteins (VLDL), high density lipoproteins (HDL) in COPD patients and correlating FEV1 and FEV1/FVC ratio with lipid profile. Settings and Design: A prospective cross-sectional case control study. Method: 40 COPD patients 33 males (82.5%) and 7 females (17.5%) with mean age of 53.43±9.64 years, FEV1: 52±15 % pred., BMI: 29.4 ±4.5kg/m2 with stable COPD enrolled in the study. We compared lipid profile in 40 patients with COPD and control group - 40 COPD patients. Results: Mean Cholesterol concentration was (257.30±56.39) (mg/dl), TG (Triglyceride) 253.18±58.98. LDL (191.17±86.17) (mg/dl), VLDL (51.31±11.79), HDL (30.98±5.21) (mg/dl) as against control group who had concentration of 188.58±39.59 (mg/dl), 112.56±55.44, 98.74±28.30, 31.59±11.56, 42.65±6.55 respectively. Which was statistically significant (p-value < 0.001).L/H Ratio (6.59±1.52) in cases compared to control Mean 3.98±1.84.C-RP mean concentration in cases 3.26±2.0, compared to control 0.48±0.38. Conclusion: The study established that there is decreased serum HDL LEVEL and increased cholesterol, TG, LDL, VLDL,L/H, C-RP, BMI in patients with COPD suggest C-Reactive Protein (HS-CRP) is considered as a marker of systemic inflammation. Increased LDL, cholesterol levels and decreased HDL cholesterol levels are indicative of an atherogenic lipid pattern. Keywords: COPD, C-RP, Lipid Profile, Dyslipidemia, Systemic Inflammation

Untargeted UHPLC-ESI-QTOF-MS/MS analysis with targeted feature extraction at precursor and fragment level for profiling of the platelet lipidome with ex vivo thrombin-activation

Lipids play a major role in platelet signaling and activation. In this study, we analyzed the platelet lipidome in an untargeted manner by reversed-phase UHPLC for lipid species separation coupled to high-resolution QTOF-MS/MS in data-independent acquisition (DIA) mode with sequential window acquisition of all theoretical fragment ion mass spectra (SWATH) for compound detection. Lipid identification and peak picking was supported by the characteristic regular elution pattern of lipids differing in carbon and double bond numbers. It was primarily based on post-acquisition targeted feature extraction from the SWATH data. Multiple extracted ion chromatograms (EICs) from SWATH data of diagnostic ions on MS1 and MS2 level from both positive and negative ion mode allowed to distinguish between poorly resolved isomeric lipids based on their distinct fragment ions, which were used for relative quantification at a molecular lipid species level. It supports assay specificity for relative lipid quantitation via multiple quantifiably ions unlike to data-dependent acquisition methods which rely on precursor ions only. This approach was used to analyze human platelet samples. 457 lipids were annotated. Concentrations of lipids were estimated by stable isotope-labelled lipid class-specific internal standards as surrogate calibrants. Heatmaps of lipid concentrations in dependence on carbon and double bond numbers for the distinct lipid classes revealed a snapshot of the platelet lipidome in the resting state with lipid species distributions within classes supporting some functional interpretations. As expected, activation of the platelets by thrombin has led to significant alterations in the platelet lipidome as proven by univariate (volcano plot) and multivariate (PLS-DA) statistics. Several lipids were significantly up-regulated (lysophosphatidylinositols, oxylipins such as thromboxane B2 (TXB2), hydroxyheptadecatrienoic acid (HHT), hydroxyeicosatetraenoic acid (HETE), hydroxyoctadecadienoic acid (HODE), sphingoid-bases, (very) long chain saturated fatty acids) or down-regulated (lysophosphatidylethanolamines, polyunsaturated fatty acids, phosphatidylinositols). Several of them are well known as biomarkers of platelet activation while others may provide some further insights into pathways of platelet activation and platelet metabolism.

Determination of maintenance Jarlsberg® cheese dose to keep the obtained serum osteocalcin level; a response surface pathway designed de-escalation dose study with individual starting values

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Daily maximum effective dose (MED) of Jarlsberg® increased the serum osteocalcin (tOC) level, vitamin K2 and affected the lipid pattern positively. The aim of the study was to estimate and verify a daily maintenance dose.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 12 healthy female volunteers (HV) were included in a de-escalation study after a six week run-in period on the daily MED of 57 g Jarlsberg® cheese. A 3-level within-patient response surface pathway (RSP) design with individual starting values was developed. Another 12 HVs were included in a new study with a six week run-in period on MED followed with six weeks on the estimated maintenance dose. All HVs were premenopausal female between 20 and 52 years of age. The main variable in the studies was the tOC level.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; tOC, cOC and the vitamin K2 variants increases significantly (p&amp;lt;0.01) during the run-in period on daily MED of Jarlsberg® in both studies. The maintenance daily dose was estimated to 45 g (95% CI: 38-52 g/day) and used in the new study. The tOC level was reduced from 19.8 ng/ml (95% CI: 12.0-27.6) obtained in the run-in period to 18.5 ng/ml (95% CI: 11.7-25.3) during the maintenance part. This represents a reduction of 6.6%. The sum of vitamin K2 variants changed from 0.58 ng/ml on MED of Jarlsberg® to 0.59 ng/ml (95% CI: 0.37-0.82) during the maintenance period.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Daily MED of Jarlsberg® cheese increases tOC, cOC and the vitamin K2 level. The maintenance Jarlsberg® dose was estimated to 45 g/day and verified as sufficient.&lt;/p&gt;

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

Lipidomic Analysis to Assess Oxidative Stress in Acute Coronary Syndrome and Acute Stroke Patients.

Alterations in lipid metabolism mediated by oxidative stress play a key role in the process of atherosclerosis and superimposed thrombosis; these can lead to acute coronary syndrome (ACS) and acute ischemic stroke (AIS). Multiple studies have shown that the formation of atheromatous lesions is initiated by oxidation of low-density lipoproteins incorporated into the intima of the vessel wall. Here, we studied lipids in plasma samples from three cohorts: 61 patients with ACS (group A), 49 patients with AIS (group D), and 82 controls (group K). Untargeted lipidomics based on high-performance liquid chromatography coupled to mass spectrometry (UHPLC-HRMS) was employed to obtain comprehensive information on whether relationships exist between these patient categories based on lipid patterns. In addition, malondialdehyde (MDA) as a standard marker of oxidative stress was monitored. The most characteristic lipids in group K were fatty acyls of hydroxyfatty acids (FAHFAs). As expected, MDA concentrations were the lowest in group K. Our findings can better explain ongoing pathologies, both acute and chronic, with the potential for future diagnosis and treatment.

Halomonas azerica sp. nov., Isolated from Urmia Lake in Iran.

A novel moderately halophilic, Gram-staining negative and facultative aerobic bacterium, designated as TBZ9T, was isolated from water of Urmia Lake in Azerbaijan region of Iran. The cells were found to be rod-shaped and motile, growing in the form of creamy, convex and shiny colonies. The strain could grow in the presence of NaCl at concentrations 1-17% (w/v) (optimum, 3%), temperatures 10-40°C (optimum, 30°C) and pH 6.0-11.0 (optimum, pH 7.0) on marine agar. Strain TBZ9T 16S rRNA gene sequence was related to the genus Halomonas showing highest similarities to Halomonas arcis AJ282T (98.4%), Halomonas songnenensis NEAU-ST10-39T (98.0%) and Halomonas lutescens Q1UT (97.8%). In the phylogenetic trees, strain TBZ9T formed a distinct branch closely related to a subclade inside the Halomonas genus. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain TBZ9T and H. arcis AJ282T (20.0%, 74.0%) and H. songnenensis NEAU-ST10-39T (19.8%, 75.2%) indicated that TBZ9T represents a distinct species. Evaluation of fatty acid contents determined C10:0, C16:0, C12:0 3-OH, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) as major cellular fatty acids. The major quinone of strain TBZ9T was Q-9. Polar lipid patterns consisted of phosphatidylglycerol (PG), phosphatidylethanolamine (PE), two unidentified phospholipids (PL) and four unidentified polar lipids (L). The average DNA G + C content of strain TBZ9T is 55.4mol%. Results from phenotypic, chemotaxonomic and molecular analysis suggest that the strain TBZ9T represents a novel species within the genus Halomonas for which the name Halomonas azerica sp. nov. is proposed. The type strain is TBZ9T (= KACC 21783T = LMG 25775T).

Distribution of polyprenol and dolichol in oil palms from Pisifera parents and mature plants from tissue culture propagation

Abstract. Kartika EBA, Siregar LAM, Basyuni M. 2021. Distribution of polyprenol and dolichol in oil palms from Pisifera parents and mature plants from tissue culture propagation. Biodiversitas 22: 3423-3436. Oil palm tissue culture is carried out through indirect embryogenesis, which causes somaclonal diversity to occur at the in vitro propagation stage, especially in the callus growth phase. In the cells of all living organisms can be found a group of polyisoprenoid compounds. This study aims to determine variations in oil palm plants resulting from tissue culture based on the presence of polyisoprenoid compounds. Oil palm leaf samples (Elaeis guineensis Jacq.) were collected from the plantation of PT. Socfin Indonesia, North Sumatra, Indonesia. Sample extraction, saponification, isolation of polyisoprenoid compounds, and two-dimensional thin-layer chromatography analysis were carried out to obtain data related to total lipids, polyprenol and dolichol profile, and Carbon (C) chain length polyprenol and dolichol from oil palm leaves of Pisifera parents and their propagated derivatives by indirect embryogenesis. The results showed that the amount of polyisoprenoid mother S24 was 2.41 mg/g higher than that of the parentS8 at 2.17 mg/g dry weight. Total polyisoprenoid fromS8 plants in vitro ranged from 0.71 - 8.53 mg/g dry weight, with the lowest total polyisoprenoid found atS894/22 and the highest was found atS893/2. While for total polyisoprenoid from plant tissue culture of Pisifera S24 ranged from 0.73 - 8.05 mg/g dry weight, with the lowest total polyisoprenoid found at S24H14 and the highest was found at S24H16. The parent plants of Pisifera S8 and S24, as well as plants resulting from tissue culture, were categorized as having lipid pattern type II, which showed a balanced distribution of polyprenol with dolichol. The longest carbon chain was found in vitro plantsS8 93/4 ranged from C50-C110, while the shortest was found in plants produced in vitro S24H7 starting from C45-C55. There were variations in the carbon chain length of polyprenol and dolichol in the leaf samples derived from in vitro propagation of the Pisifera S8 and S24 parents.

298-OR: Lipid Pattern in Men with Hypogonadism and Type 2 Diabetes Improves during Long-Term Treatment with Testosterone Undecanoate Injections (TU) in Comparison with an Untreated Control Group: Update of Real-World Registry Data

Background: Previous studies reported inconsistent effects of testosterone therapy on the lipid profile in men with hypogonadism. Methods: Of 361 men with hypogonadism and T2DM, 183 received TU 1000 mg/12 weeks (T-group), 178 opted against treatment (CTRL). Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups. Results: Mean follow-up 8.7±3.1, baseline age: 61.8±5.3 years. Total cholesterol (mmol/L for all lipids) decreased by 2.9±0.1 (unadjusted from 8.3±1.1 to 5.2±0.3) at 12 years in T-group and increased by 1.3±0.1 (7.1±1.2 to 8.2±1.4) in CTRL. (p&amp;lt;0.0001 for both). HDL increased by 0.5±0.0 (1.0±0.4 to 1.6±0.4) in T-group and decreased by 0.3±0.0 (1.1±0.5 to 0.1±0.4) in CTRL (p&amp;lt;0.0001 for both). The total cholesterol:HDL ratio decreased by 5.6±0.3 (9.7±4.3 to 3.4±0.7) in T-group and increased by 5.5±0.3 (8.0±3.9 to 12.1±6.1) in CTRL. (p&amp;lt;0.0001 for both). LDL decreased by 1.9±0.1 (4.7±0.9 to 2.6±0.2) in T-group and increased by 1.0±0.1 (4.1±1.4 to 4.9±1.5) in CTRL (p&amp;lt;0.0001 for both). Triglyceride decreased by 1.1±0.0 (3.5±0.6 to 2.2±0.1) in T-group and increased by 0.6±0.0 (3.1±0.6 to 3.7±0.5) in CTRL (p&amp;lt;0.0001 for both). Non-HDL decreased by 3.4±0.1 (7.3±1.2 to 3.6±0.3) in T-group and increased by 1.6±0.1 (6.0±1.4 to 7.4±1.5) in CTRL (p&amp;lt;0.0001 for both). Remnant cholesterol decreased by 1.5±0.1 (2.6±1.0 to 0.9±0.3) in T-group and increased by 0.6±0.1 (2.0±1.0 to 2.4±0.7) in CTRL (p&amp;lt;0.0001 for both). The triglyceride:HDL ratio decreased by 5.3±0.4 (9.4±4.4 to 3.2±0.8) in T-group and increased by 5.7±0.4 (8.0±4.1 to 12.5±6.0) in CTRL (p&amp;lt;0.0001 for both). Conclusions: Long-term treatment with TU in men with hypogonadism and T2DM progressively improved the lipid profile, which worsened in controls. Disclosure F. Saad: Consultant; Self; Bayer AG, Stock/Shareholder; Self; AbbVie Inc., Bayer AG, Novo Nordisk. K. S. Haider: Other Relationship; Self; Bayer AG. A. Haider: Other Relationship; Self; Bayer AG. Funding Bayer AG

Effect of Katakakhadiradi Kashayam on Lipid Profile and Pancreatic Damage in Type II Diabetes Mellitus

The lipid pattern and levels in diabetic patient are the same as those for subjects with cardiovascular disease. The tactic underlying the oral hypoglycemic agent is to adjust the lipid profile; which can be achieved by herbal therapy. The use of herbs and formulations for attenuation of hyperglycemia and to aid protection against the pancreatic damage is clinically very important. This study was intended to find the efficacy of Katakakhadiradi Kashayam(KKK)on lipid profile and pancreatic tissue damage in streptozotocin-nicotinamide (SN) induced diabetic rats. The diabetic rats were treated with Katakakhadiradi Kashyam orally at doses of 100, 200 and 300 mg/kg/bw. For 28 days and compared with the standard drug Glibenclamide. After the kashayam treatment triglyceride, HDL-cholesterol and total cholesterol level were assayed and pancreatic tissue damage caused by streptozotocin was analysed by histology study.Katakakhadiradi kashayam could restore the serum lipid profile by controlling the blood glucose level and reduce the pancreatic injury in diabetic rats. Supplementation of Katakakhadiradi kashayam showed a significant improvement in the serum lipid profile thus helping in retarding the secondary complications.

Variation of salinity and nitrogen concentration affects the pentacyclic triterpenoid inventory of the haloalkaliphilic aerobic methanotrophic bacterium Methylotuvimicrobium alcaliphilum

The occurrence and activity of aerobic methanotrophs are influenced by environmental conditions, including pH, temperature, salinity, methane and oxygen concentrations, and nutrient availability. Aerobic methanotrophs synthesize a variety of lipids important for cell functions. However, culture-based experiments studying the influence of environmental parameters on lipid production by aerobic methanotrophs are scarce. Such information is crucial to interpret lipid patterns of methanotrophic bacteria in the environment. In this study, the alkaliphilic strain Methylotuvimicrobium alcaliphilum was cultivated under different salinities and different nitrate concentrations to assess the effect of changing conditions on the inventory of pentacyclic triterpenoids. The results indicate that hopanoid abundance is enhanced at lower salinity and higher nitrate concentration. The production of most pentacyclic triterpenoids was favored at low salinity, especially for aminotriol. Interestingly, 3-methyl-aminotetrol and tetrahymanol were favored at higher salinity. Bacteriohopanepolyols (BHPs), particularly aminotriol and 3-methyl-aminotriol, increased considerably at higher nitrate concentrations. Four novel N-containing BHPs—aminodiol, 3-methyl-aminodiol, and isomers of aminotriol and 3-methyl-aminotriol—were identified. This study highlights the significance of environmental factors for bacterial lipid production and documents the need for cultivation studies under variable conditions to utilize the full potential of the biomarker concept.

EFFECTIVENESS AND SAFETY OF NUTRACEUTICAL COMPOUNDS ADDED TO EZETIMIBE TREATMENT IN HYPERTENSIVE AND HYPER–CHOLESTEROLEMIC SUBJECTS WITH STATIN–INTOLERANCE

Objective: The effectiveness of statins in the primary and secondary prevention of cardiovascular (CV) diseases has been widely proven. However, the onset of adverse events associated with their use, prevents to achieve the therapeutic targets recommended by the guidelines (GL) for the management of dyslipidaemia. In the event of statin intolerance, is recommend to use bile acid sequestrants, fibrates and ezetimibe in monotherapy, but their benefits in improving lipid pattern are quite modest. This study aims at evaluating the effectiveness and safety of a nutraceutical compound (NC) associated with ezetimibe (E) on the lipid profile in statin-intolerant patients with moderate-to-high CV risk Design and method: Ninety-six statin-intolerant hypertensive and hyper-cholesterolemic subjects treated with E 10 mg daily, were randomised in open label (n = 48) to take for 3 months a NC containing Monacolin K (MK) 5 mg, Berberine Hydrochloride, t-Resveratrol, Quercetin, and Chromium, in the form of a gastro-resistant tablet that improves enteric bio-accessibility and bio-availability of these substances. The control group (n = 48), took only E in monotherapy at the same dosage; both groups followed a standardised lipid-lowering diet. The total serum cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine phosphokinase (CPK) levels were compared at the follow-up in both groups using Student's t-test. Results: TC and LDL levels reduced in both groups, but there lower in the group treated with E+ NC vs E alone (-25.9 vs -15%, p &lt; 0.05 and -38.7 vs. -21.0%, p &lt; 0.05, respectively). No changes were observed in either group regarding to a decrease in TG (-9.4 vs. -11.7%, NS) and an increase in HDLC (+ 4.2 vs. +1.1%, NS). The AST, ALT and CPK levels increased in the E + NC compared to the control group, but were still within the acceptable range. There was no difference for the lipid-lowering treatment between gender, and no patient withdrawn the study. Conclusions: In hypertensive and hyper-cholesterolemic subjects with statin-intolerance, the E + NC combination therapy is well-tolerated and effective in the short term in improving TC and LDLC levels.

The Role of Cholesterol and Fatty Acids in the Etiology and Diagnosis of Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders whose pathogenesis seems to be related to an imbalance of excitatory and inhibitory synapses, which leads to disrupted connectivity during brain development. Among the various biomarkers that have been evaluated in the last years, metabolic factors represent a bridge between genetic vulnerability and environmental aspects. In particular, cholesterol homeostasis and circulating fatty acids seem to be involved in the pathogenesis of ASDs, both through the contribute in the stabilization of cell membranes and the modulation of inflammatory factors. The purpose of the present review is to summarize the available data about the role of cholesterol and fatty acids, mainly long-chain ones, in the onset of ASDs. A bibliographic research on the main databases was performed and 36 studies were included in our review. Most of the studies document a correlation between ASDs and hypocholesterolemia, while the results concerning circulating fatty acids are less univocal. Even though further studies are necessary to confirm the available data, the metabolic biomarkers open to new treatment options such as the modulation of the lipid pattern through the diet.

Lipid responses to environmental perfluoroalkyl substance exposure in a Taiwanese Child cohort

Although recent epidemiologic studies have focused on some of the health effects of perfluoroalkyl substance (PFASs) exposure in humans, the associations between PFASs exposure and the lipidome in children are still unclear. The purpose of this study was to assess lipid changes in children to understand possible molecular events of environmental PFASs exposure and suggest potential health effects. A total of 290 Taiwanese children (8–10 years old) were included in this study. Thirteen PFASs were analyzed in their serum by high-performance liquid chromatography-tandem mass spectrometry (LC-MS). MS-based lipidomic approaches were applied to examine lipid patterns in the serum of children exposed to different levels of PFASs. LC coupling with triple quadrupole MS technology was conducted to analyze phosphorylcholine-containing lipids. Multivariate analyses, such as partial least squares analysis along with univariate analyses, including multiple linear regression, were used to analyze associations between s exposure and unique lipid patterns. Our results showed that different lipid patterns were discovered in children exposed to different levels of specific PFASs, such as PFTrDA, PFOS, and PFDA. These changes in lipid levels may be involved in hepatic lipid metabolism, metabolic disorders, and PFASs-membrane interactions. This study showed that lipidomics is a powerful approach to identify critical PFASs that cause metabolite perturbation in the serum of children and suggest possible adverse health effects of these chemicals in children.

Adaptive evolution of engineered yeast for squalene production improvement and its genome-wide analysis.

In the present study, the adaptive evolution of a metabolically engineered Saccharomyces cerevisiae strain in the presence of an enzyme inhibitor terbinafine for enhanced squalene accumulation via serial transfer leads to the development of robust strains. After adaptation for nearly 1500 h, a strain with higher squalene production efficiency was identified at a specific growth rate of 0.28 h-1 with a final squalene titer of 193 mg/L, which is 16.5-fold higher than the BY4741 and 3-fold higher over the metabolically engineered SK22 strain. Whole-genome sequencing comparison between the reference strain and the evolved variant SK23 has led to the identification of 462 single-nucleotide variants (SNVs) between both strains, with 102 SNVs affecting metabolism-related genes. It was also established that F420I mutation of ERG1 in S. cerevisiae improves squalene synthesis. Further, the effect of increased squalene on lipid droplet and neutral lipid pattern in the evolved mutant strains was investigated by fluorescent techniques proving that the neutral lipid content and clustering of lipid droplets increase with an increase in squalene.

Cerebral Insulin Bolus Revokes the Changes in Hepatic Lipid Metabolism Induced by Chronic Central Leptin Infusion.

Central actions of leptin and insulin on hepatic lipid metabolism can be opposing and the mechanism underlying this phenomenon remains unclear. Both hormones can modulate the central somatostatinergic system that has an inhibitory effect on growth hormone (GH) expression, which plays an important role in hepatic metabolism. Using a model of chronic central leptin infusion, we evaluated whether an increase in central leptin bioavailability modifies the serum lipid pattern through changes in hepatic lipid metabolism in male rats in response to an increase in central insulin and the possible involvement of the GH axis in these effects. We found a rise in serum GH in leptin plus insulin-treated rats, due to an increase in pituitary GH mRNA levels associated with lower hypothalamic somatostatin and pituitary somatostatin receptor-2 mRNA levels. An augment in hepatic lipolysis and a reduction in serum levels of non-esterified fatty acids (NEFA) and triglycerides were found in leptin-treated rats. These rats experienced a rise in lipogenic-related factors and normalization of serum levels of NEFA and triglycerides after insulin treatment. These results suggest that an increase in insulin in leptin-treated rats can act on the hepatic lipid metabolism through activation of the GH axis.

Real-time lipid patterns to classify viable and necrotic liver tumors

AbstractReal-time tissue classifiers based on molecular patterns are emerging tools for fast tumor diagnosis. Here, we used rapid evaporative ionization mass spectrometry (REIMS) and multivariate statistical analysis (principal component analysis–linear discriminant analysis) to classify tissues with subsequent comparison to gold standard histopathology. We explored whether REIMS lipid patterns can identify human liver tumors and improve the rapid characterization of their underlying metabolic features. REIMS-based classification of liver parenchyma (LP), hepatocellular carcinoma (HCC), and metastatic adenocarcinoma (MAC) reached an accuracy of 98.3%. Lipid patterns of LP were more similar to those of HCC than to those of MAC and allowed clear distinction between primary and metastatic liver tumors. HCC lipid patterns were more heterogeneous than those of MAC, which is consistent with the variation seen in the histopathological phenotype. A common ceramide pattern discriminated necrotic from viable tumor in MAC with 92.9% accuracy and in other human tumors. Targeted analysis of ceramide and related sphingolipid mass features in necrotic tissues may provide a new classification of tumor cell death based on metabolic shifts. Real-time lipid patterns may have a role in future clinical decision-making in cancer precision medicine.Real-time lipid patterns can identify liver tumors and their inter-tumor and intra-tumor heterogeneity. Ceramides and related sphingolipids are a common feature of necrotic tumors and can characterize the tumor phenotype based on metabolic shifts relevant for cell death pathways. Lipid patterns have the potential to improve clinical decision-making in the near future.

Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors

Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated β- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine.