Altered Lipid Research Articles

Estimated impact of inclisiran treatment on hyperlipidemia prevalence and cardiovascular disease events in NHANES dataset

Abstract Background Inclisiran, administered subcutaneously every 6 months, will result in the reduction of LDL-cholesterol levels of approximately 50%. We estimated the eligibility of the US population for Inclisiran treatment and its impact on blood lipids and CVD events. Methods We applied ORION trial eligibility criteria to US adults aged ≥ 18 years in the US NHANES 1999-2018 to estimate the US eligible population. Blood lipid alterations in ORION 10 were applied to estimate the impact on LDL-C levels and hyperlipidemia prevalence in the ASCVD population sample. We also used the Framingham CVD risk scores to estimate 10-year CVD risks in the ASCVD high-risk population sample based on ORION 11. The difference in estimated risks with and without Inclisiran administration, multiplied by the eligible population from NHANES data, represented the potentially preventable CVD events. Results We identified 651 ASCVD persons (projected to 5.55 million) who fit ORION 10 trial eligibility criteria and 359 ASCVD high-risk persons (projected to 2.53 million) who fit ORION 11 trial eligibility criteria for our analysis. We then analyzed the changes in these populations after Inclisiran treatment. Firstly, we estimated that approximately 3.9 million (72.8%) individuals would experience ≥50% LDL-C reductions. Secondly, we estimated that among the ASCVD patients, 5.07 million (91.3%) with elevated LDL-C, 0.25 million (22.8%) with reduced HDL-C, 1.24 million (95.2%) with elevated TC, and 0.65 million (32.4%) with elevated TG would potentially achieve a more reasonable blood lipid level. Finally, among those without CVD, the estimated 10-year CVD risks were 19% before and 13.8% after Inclisiran treatment, reflecting a 5.2% absolute (and 27.4% relative) reduction in risk translating to potentially 130,000 preventable CVD events over 10 years. Conclusion Inclisiran treatment in eligible US adults may substantially reduce hyperlipidemia prevalence and CVD events.core graphics

Gestational Diabetes-like Fuels Impair Mitochondrial Function and Long-Chain Fatty Acid Uptake in Human Trophoblasts.

In the parent, gestational diabetes mellitus (GDM) causes both hyperglycemia and hyperlipidemia. Despite excess lipid availability, infants exposed to GDM are at risk for essential long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Isotope studies have confirmed less LCPUFA transfer from the parent to the fetus, but how diabetic fuels impact placental fatty acid (FA) uptake and lipid droplet partitioning is not well-understood. We evaluated the effects of high glucose conditions, high lipid conditions, and their combination on trophoblast growth, viability, mitochondrial bioenergetics, BODIPY-labeled fatty acid (FA) uptake, and lipid droplet dynamics. The addition of four carbons or one double bond to FA acyl chains dramatically affected the uptake in both BeWo and primary isolated cytotrophoblasts (CTBs). The uptake was further impacted by media exposure. The combination-exposed trophoblasts had more mitochondrial protein (p = 0.01), but impaired maximal and spare respiratory capacities (p < 0.001 and p < 0.0001), as well as lower viability (p = 0.004), due to apoptosis. The combination-exposed trophoblasts had unimpaired uptake of BODIPY C12 but had significantly less whole-cell and lipid droplet uptake of BODIPY C16, with an altered lipid droplet count, area, and subcellular localization, whereas these differences were not seen with individual high glucose or lipid exposure. These findings bring us closer to understanding how GDM perturbs active FA transport to increase the risk of adverse outcomes from placental and neonatal lipid accumulation alongside LCPUFA deficiency.

Alkaline Mineral Complex Water Attenuates Transportation-Induced Hepatic Lipid Metabolism Dysregulation by AMPKα-SREBP-1c/PPARα Pathways.

Transportation, an unavoidable process in livestock farming, causes metabolic disorders in the body, which then lead to endocrine disruption, being immunocompromised, and growth suppression. Lipid metabolism dysregulation is a critical phenotype induced by transportation. The liver is a vital organ in lipid metabolism, with a role in both lipid synthesis and lipolysis. However, the specific mechanisms by which transportation affects hepatic lipid metabolism remain unclear. This study employed rats as a model to investigate the effects of transportation on hepatic lipid metabolism. Rats subjected to transportation showed altered serum lipid profiles, including decreased serum triglyceride (TG), low-density lipoprotein cholesterol (VLDL-C), and non-esterified fatty acid (NEFA) immediately after transportation (IAT) and serum total cholesterol (TC) on day 3, and increasing serum TG, TC, and low-density lipoprotein cholesterol (LDL-C) on day 10. Meanwhile, fatty droplets in the liver were also reduced at IAT and increased on days 3 and 10. Notably, transportation also affected hepatic-lipid-metabolism-related enzyme activities and signaling pathways, such as increased AMP-activated protein kinase alpha (AMPKα) phosphorylation and modulations in key proteins and genes related to lipid metabolism, decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) activities at IAT, and increased carnitine palmitoyl transferase 1 alpha (CPT-1α) at IAT and ACC and CPT-1α activities on days 3 and 10. Supplementation with alkaline mineral complex water (AMC) before and after transportation mitigated the adverse effects on hepatic lipid metabolism by modulating the AMPKα-SREBP-1c/PPARα pathway, enhancing lipid synthesis, and reducing the oxidative catabolism of fatty acids. AMC inhibited the transportation-induced activation of AMPKα and restored the balance of lipid-metabolism-related enzymes and pathways. These findings highlight AMC's potential as a therapeutic intervention to alleviate transportation-induced lipid metabolism disorders, offering significant implications for improving animal welfare and reducing economic losses in livestock farming.

Effect of Moderate Beer Intake on the Lipid Composition of Human Red Blood Cell Membranes.

Background/Objectives: Growing evidence suggests that erythrocyte membrane lipids are subject to changes during their lifespan. Factors such as the type of dietary intake and its composition contribute to the changes in red blood cell (RBC) membranes. Due to the high antioxidant content of beer, we aimed to investigate the effect of moderate beer consumption on the lipid composition of RBCs membranes from healthy overweight individuals. Methods: We conducted a four-weeks, prospective two-arm longitudinal crossed-over study, where participants (n = 36) were randomly assigned to alcohol-free beer group or traditional beer group. The lipids of RBCs membranes were assessed at the beginning and the end of the intervention by thin-layer chromatography. Results: Four-weeks of alcohol-free beer promoted changes in fatty acids (FA), free cholesterol (FC), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (p < 0.05). Meanwhile, traditional beer intake led to changes in FA, FC, phospholipids (PL), PE and PC (p < 0.05). The observed alterations in membrane lipids were found to be independent of sex and BMI as influencing factors. Conclusions: The lipid composition of erythrocyte membranes is distinctly but mildly influenced by the consumption of both non-alcoholic and conventional beer, with no effects on RBC membrane fluidity.

EVALUATION OF LIPID PROFILE OF HYPERTENSIVE PREGNANT WOMEN ATTENDING MGBAKWU PRIMARY HEALTH CARE CENTRE, ANAMBRA STATE

Hypertension is a serious global public health problem. Serum lipid alteration is a pivotal factor that births hypertension during pregnancy and has been implicated in diverse deleterious health outcomes. Thus, the aim of this study was to evaluate the lipid profiles of hypertensive pregnant women attending Mgbaukwu Primary Health Care (PHC) Centre. A total of 70 pregnant women who had consented were recruited to participate. While thirty five (35) pregnant women were hypertensive, the other remaining 35 pregnant women were not hypertensive (normotensive) and thus, were considered the control group. Socio-demographic characteristics of the participants were generated using structured questionnaire, while lipid profiles of the participants were determined using standard procedures. Results obtained from this study shows that 80% and 34.28% of the hypertensive and normotensive pregnant women respectively were within the age range of 32-37 years old, while 68.6% and 48.57% of the hypertensive and normotensive pregnant women respectively were traders and had completed only secondary school education. The value recorded on Total Cholesterol (TC) , Very Low Density Lipoprotein (VLDL), Low Density Lipoprotein (LDL), and Triglycerol (TG) in Hypertensive Pregnant Women (HYPW) were significantly (p&lt;0.05) higher than those reported for their normotensive counterparts. In conclusion, it can be deduced from this study that pregnant women who are within 32-37 years of age are prone to hypertension during pregnancy, while social determinants of health (SDOH) can support incidence of hypertension.

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study

BackgroundBreast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.MethodsPlasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.ResultsBefore initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ2 = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15–48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.ConclusionPostmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.Trial registration The clinical trial (registration number NCT03784651) was registered on www.clinicaltrials.gov on 24 December 2018.

Normocalcemic primary hyperparathyroidism is not associated with cardiometabolic alterations.

Cardiometabolic disorders are non-classical complications of hypercalcemic primary hyperparathyroidism (HC-PHPT), but whether this risk connotes normocalcemic PHPT (NC-PHPT) remains to be elucidated. We investigated cardiometabolic alterations in both forms of PHPT, looking for their association with indices of disease activity. Patients with HC-PHPT (n = 17), NC-PHPT (n = 17), and controls (n = 34) matched for age, sex, and BMI were assessed for glucose, lipid, blood pressure alterations, and history of cardiovascular events to perform a case-control study at an ambulatory referral center for Bone Metabolism Diseases. NC-PHPT, in comparison to controls, showed similar glucose (mean ± SD, 88 ± 11 vs 95 ± 22 mg/dl), total cholesterol (199 ± 25 vs 207 ± 36 mg/dl), and systolic blood pressure levels (SBP, 132 ± 23 vs 132 ± 19 mmHg), together with a comparable frequency of glucose alterations (6% vs 9%), lipid disorders (41% vs 50%) and hypertension (53% vs 59%, p = NS for all comparisons). Conversely, all these abnormalities were more prevalent in HC-PHPT vs controls (p < 0.05). When compared to NC-PHPT, HC-PHPT showed higher glucose (113 ± 31 mg/dl), total cholesterol (238 ± 43 mg/dl), and SBP levels (147 ± 15 mmHg) as well as an increased frequency of glucose (41%) and lipid alterations (77%) and a higher number of cardiovascular events (18% vs 0%, p < 0.05 for all comparisons). Among indices of PHPT activity, calcium levels displayed a significant correlation with glucose (R = 0.46) and SBP values (R = 0.60, p < 0.05). NC-PHPT is not associated with cardiovascular alterations. The predominant pathogenetic role of hypercalcemia in the development of cardiometabolic disorders could account for the absence of such alterations in NC-PHPT.

Surgical removal of tonsils and risk of COVID-19: a nested case–control study using data from UK Biobank and AMORIS Cohort

BackgroundTo investigate the association between surgical removal of tonsils and risk of COVID-19 with different severity.MethodsThrough a nested case–control study during January 31st to December 31st 2020, including 58,888 participants of the UK Biobank, we investigated the association of tonsillectomy with the future risk of mild and severe COVID-19, using binomial logistic regression. We further examined the associations of such surgery with blood inflammatory, lipid and metabolic biomarkers to understand potential mechanisms. Finally, we replicated the analysis of severe COVID-19 in the Swedish AMORIS Cohort (n = 451,960).ResultsTonsillectomy was associated with a lower risk of mild (odds ratio [95% confidence interval]: 0.80 [0.75–0.86]) and severe (0.87 [0.77–0.98]) COVID-19 in the UK Biobank. The associations did not differ substantially by sex, age, Townsend deprivation index, or polygenic risk score for critically ill COVID-19. Levels of blood inflammatory, lipid and metabolic biomarkers did, however, not differ greatly by history of surgical removal of tonsils. An inverse association between tonsillectomy and severe COVID-19 was also observed in the AMORIS Cohort, primarily among older individuals (> 70 years) and those with ≤ 12 years of education.ConclusionsSurgical removal of tonsils may be associated with a lower risk of COVID-19. This association is unlikely attributed to alterations in common blood inflammatory, lipid and metabolic biomarkers.

Altered metabolic profiles in male offspring conceived from intracytoplasmic sperm injection

BackgroundWhile most research has focused on the association between intracytoplasmic sperm injection (ICSI) and neurodevelopmental disorders in children, relatively little attention has been given to its metabolic effects. Previous studies have reported that low serum lipid levels are associated with mental health problems. Our objective was to analyze the impact of ICSI on metabolic alterations compared to their in vitro fertilization (IVF) counterparts in male offspring, as well as its interaction with paternal overweight/obesity.MethodsWe recruited families between January 2006 and December 2017 at the Center for Reproductive Medicine, Shandong University, China. Prospective data of offspring were obtained for body mass index (BMI), blood pressure, glucose, and lipid profile in their 0–11 years old. Linear mixed models were utilized to compute the mean difference and 95% confidence intervals (CI).ResultsA total of 14,196 offspring visits were identified. In offspring aged 4–11 years, ICSI-conceived offspring exhibited significantly lower fasting glucose z-scores, total cholesterol z-scores, and low-density lipoprotein cholesterol (LDL-C) z-scores compared with their IVF counterparts (fasting glucose z-score: adjusted mean difference: − 0.13, 95% CI: − 0.23 to − 0.03; total cholesterol z-score: adjusted mean difference: − 0.13, 95% CI: − 0.23 to − 0.02; LDL-C z-score: adjusted mean difference: − 0.12, 95% CI: − 0.22 to − 0.01). Paternal overweight/obesity significantly influenced the relationship between ICSI and metabolic changes in offspring. In offspring born from fathers with overweight/obesity, ICSI-conceived offspring displayed significantly lower fasting glucose and total cholesterol z-scores than their IVF controls (fasting glucose z-score: adjusted mean difference: − 0.20, 95% CI: − 0.32 to − 0.08; total cholesterol z-score: adjusted mean difference: − 0.15, 95% CI: − 0.27 to − 0.02). In offspring born to fathers with normal weight, ICSI-conceived offspring showed significantly lower systolic blood pressure z-scores compared to those conceived via the IVF procedures (adjusted mean difference: − 0.21, 95% CI: − 0.37 to − 0.05).ConclusionsThe findings of this study suggested that ICSI was associated with altered glucose and lipid profiles compared to their IVF controls, characterized by lower fasting glucose z-scores, total cholesterol z-scores, and LDL-C z-scores. Encouraging fathers to reduce their body weight could potentially improve the metabolic health of their ICSI-conceived children.

Mass Spectrometry Imaging of Two Neocortical Areas Reveals the Histological Selectivity of Schizophrenia-Associated Lipid Alterations.

Schizophrenia is a psychiatric disorder known to affect brain structure and functionality. Structural changes in the brain at the level of gross anatomical structures have been fairly well studied, while microstructural changes, especially those associated with changes in the molecular composition of the brain, are still being investigated. Of special interest are lipids and metabolites, for which some previous studies have shown association with schizophrenia. To utilize a spatially resolved analysis of the brain lipidome composition to investigate the degree and nature of schizophrenia-associated lipidome alterations in the gray and white matter structures of two neocortical regions - the dorsolateral prefrontal cortex (Brodmann area 9, BA9) and the posterior part of the superior temporal gyrus (Brodmann area 22, posterior part, BA22p), as well compare the distribution of the changes between the two regions and tissue types. We employed Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Imaging (MALDI-MSI), supplemented by a statistical analysis, to examine the lipid composition of brain sections. A total of 24 neocortical sections from schizophrenia patients (n=2) and a healthy control group (n=2), representing the two aforementioned neocortical areas, were studied, yielding data for 131 lipid compounds measured across more than a million MALDI-MSI pixels. Our findings revealed an uneven distribution of schizophrenia-related lipid alterations across the two neocortical regions. The BA22p showed double the differences in its subcortical white matter structures compared to BA9, while less bias was detected in the gray matter layers. While the schizophrenia-associated lipid differences generally showed good agreement between brain regions at the lipid class level for both gray and white matter, there were consistently more discrepancies for white matter structures. Our study found a consistent yet differential association of schizophrenia with the brain lipidome composition of distinct neocortical areas, particularly subcortical white matter. These findings highlight the need for broader brain coverage in future schizophrenia research and underscore the potential of spatially resolved molecular analysis methods in identifying structure-specific effects.

Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment.

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition.

Insight into the outer membrane asymmetry of P. aeruginosa and the role of MlaA in modulating the lipidic composition, mechanical, biophysical, and functional membrane properties of the cell envelope.

In Gram-negative bacteria, the outer membrane (OM) is asymmetric, with lipopolysaccharides (LPS) in the outer leaflet and glycerophospholipids (GPLs) in the inner leaflet. The asymmetry is maintained by the Mla system (MlaA-MlaBCDEF), which contributes to lipid homeostasis by removing mislocalized GPLs from the outer leaflet of the OM. Here, we ascribed how Pseudomonas aeruginosa ATCC 27853 coordinately regulates pathways to provide defense against the threats posed by the deletion of mlaA. Especially, we explored (i) the effects on membrane lipid composition including LPS, GPLs, and lysophospholipids, (ii) the biophysical properties of the OM such as stiffness and fluidity, and (iii) the impact of these changes on permeability, antibiotic susceptibility, and membrane vesicles (MVs) generation. Deletion of mlaA induced an increase in total GPLs and a decrease in LPS level while also triggering alterations in lipid A structures (arabinosylation and palmitoylation), likely to be induced by a two-component system (PhoPQ-PmrAB). Altered lipid composition may serve a physiological purpose in regulating the mechanobiological and functional properties of P. aeruginosa. We demonstrated an increase in cell stiffness without alteration of turgor pressure and inner membrane (IM) fluidity in ∆mlaA. In addition, membrane vesiculation increased without any change in OM/IM permeability. An amphiphilic aminoglycoside derivative (3',6-dinonyl neamine) that targets P. aeruginosa membranes induced an opposite effect on ∆mlaA strain with a trend toward a return to the situation observed for the WT strain. Efforts dedicated to understanding the crosstalk between the OM lipid composition, and the mechanical behavior of bacterial envelope, is one needed step for designing new targets or new drugs to fight P. aeruginosa infections.IMPORTANCEPseudomonas aeruginosa is a Gram-negative bacterium responsible for severe hospital-acquired infections. The outer membrane (OM) of Gram-negative bacteria acts as an effective barrier against toxic compounds, and therefore, compromising this structure could increase sensitivity to antibiotics. The OM is asymmetric with the highly packed lipopolysaccharide monolayer at the outer leaflet and glycerophospholipids at the inner leaflet. OM asymmetry is maintained by the Mla pathway resulting in the retrograde transport of glycerophospholipids from the OM to the inner membrane. In this study, we show that deleting mlaA, the membrane component of Mla system located at the OM, affects the mechanical and functional properties of P. aeruginosa cell envelope. Our results provide insights into the role of MlaA, involved in the Mla transport pathway in P. aeruginosa.

Dietary lipid is largely deposited in skin and rapidly affects insulating properties.

Skin has been shown to be a regulatory hub for energy expenditure and metabolism: mutations of skin lipid metabolism enzymes can change the rate of thermogenesis and susceptibility to diet-induced obesity. However, little is known about the physiological basis for this function. Here we show that the thermal properties of skin are highly reactive to diet: within three days, a high fat diet reduces heat transfer through skin. In contrast, a dietary manipulation that prevents obesity accelerates energy loss through skins. We found that skin was the largest target in a mouse body for dietary fat delivery, and that dietary triglyceride was assimilated both by epidermis and by dermal white adipose tissue. Skin from mice calorie-restricted for 3 weeks did not take up circulating lipids and showed a highly depleted stratum corneum. Dietary triglyceride acyl groups persist in skin for weeks after feeding. Using multi-modal lipid profiling, we have implicated both keratinocytes and sebocytes in the altered lipids which correlate with thermal function. In response to high fat feeding, wax diesters and ceramides accumulate, and triglycerides become more saturated. In contrast, in response to the dramatic loss of adipose tissue that accompanies restriction of the branched chain amino acid isoleucine, skin becomes more heat-permeable, resisting changes induced by Western diet feeding, with a signature of depleted signaling lipids. We propose that skin should be routinely included in physiological studies of lipid metabolism, given the size of the skin lipid reservoir and its adaptable functionality.

Antidiabetic, antihyperlipidemic effects and quantification of bioactive compounds by HPLC from Crassula ovata leaves extracts on streptozotocin induced diabetic Wistar rats

Background: Crassula ovata have been recommended in ethno medicines for the treatment of diabetes. In this research the scientific claim is studied and validated. Objective: Objective of the current study has been focused to assess the traditional use of Crassula ovata to heal diabetes, hyperlipidemia and to check the presence of constituents responsible for these actions. Methods: The approved plant's ethanol, acetone, and chloroform extracts were prepared by maceration. For in vivo activity, the model of streptozotocin induced diabetes mellitus in rats was chosen, wherein antidiabetic parameters such as body weight, urine volume, blood glucose level, and lipid profile parameters were evaluated. Quantification of bioactive compounds was done by a high-performance liquid chromatographic technique using diode-array detection. Results: The ethanolic extract noticeably depleted increased blood glucose levels and has positive effects on altered lipid profile after administering a dose of 200 mg/kg orally compared with oral hypoglycemic drug metformin. HPLC analysis of ethanolic extract identified several secondary metabolites in Crassula ovata, including Gallic acid, Rutin, Luteolin, Caffeic acid, Catechin, Kaempferol and Quercetin. These compounds have been reported for their potential antidiabetic effects. The analytical data on the chemical composition supported its traditional use in diabetes management. Conclusion: From the results, it can be concluded that, Crassula ovata ethanolic extract can be ideal for the treatment of diabetes and hyperlipidemia. Further studies are required to locate the active pharmaceutical ingredient for the said actions.

Early pregnancy serum PFAS are associated with alterations in the maternal lipidome

Per- and polyfluoroalkyl substances (PFAS) have been detected in the blood of humans and animals worldwide. Exposure to some PFAS are associated with multiple adverse pregnancy outcomes. Existing literature has identified a strong association with PFAS exposure and metabolic dysfunction in humans, including modification of lipid metabolism. Using a subset of the Michigan Mother-Infant Pairs cohort (n=95), this study investigated associations between first trimester plasma levels of PFAS and maternal lipids and metabolites in the first trimester (T1), at the time of delivery (T3), and in the infant cord blood (CB) using untargeted shotgun lipidomics and metabolomics. Identifying PFAS-induced alterations in the maternal lipid- or metabolome at specific timepoints may help elucidate windows of susceptibility to adverse pregnancy outcomes. Out of 9 PFAS measured, 7 were detected in at least 20% of samples and were used for further analyses. PFOS and PFHxS were measured at the highest concentrations with medians of 5.76 ng/ml and 3.33 ng/ml, respectively. PFOA, PFNA, and PFDA had lower measured values with medians of < 1.2 ng/mL. PFHxS concentrations were positively associated with monounsaturated sphingomyelins (SMs) in T1 maternal plasma in adjusted models, determined by an adjusted p-value (q) < 0.1. PFHxS was positively associated with saturated and polyunsaturated SMs and inversely associated with saturated diacylglycerols in T1. Following metabolite-specific analysis, two mono-unsaturated diacylglycerols with carbon chain lengths of 32 and 35 were inversely associated with PFHxS in T1. In T3, only the association between PFHxS and SMs remained, but was attenuated. In addition, PFDA was associated with an increase in polyunsaturated plasmenyl-phosphatidylethanolamines in T3. No associations were identified between PFAS and infant cord blood lipids. Continued research into PFAS associated disruptions in lipid metabolism at sensitive stages of gestation may provide insight into the mechanisms that lead to adverse birth and pregnancy outcomes.

Cancer-associated foam cells hamper protective T cell immunity and favor tumor progression in human colon carcinogenesis

BackgroundColorectal cancer (CRC) remains a significant healthcare burden worldwide, characterized by a complex interplay between obesity and chronic inflammation. While the relationship between CRC, obesity and altered lipid metabolism is...

Meibomian gland lipid alterations and ocular surface sequela in Awat2 knockout murine model of meibomian gland dysfunction and evaporative dry eye disease

PurposeThere is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints. MethodsWildtype and Awat2 KO mice between 1 and 18 months of age were used. Ocular examinations and advanced imaging were performed. The lipidomic composition and in situ melting temperature of meibum were determined. qPCR was performed to define ocular surface gene and pro-inflammatory transcript expression. Dynamic contact angle goniometry was performed to assess the adherence capability of the ocular surface. ResultsAwat2 KO mice have mild, white, hyperreflective corneal opacities of the anterior stroma and significantly enlarged apical epithelial cells (P=0.0004). In Awat2 KO meibum, wax esters were 9-10 times lower than in wildtype meibum. Additionally, meibum melting temperature increased from 32° to 47°C (P<0.0001), leading to impaired meibum secretion and dilation of the central duct. Awat2 KO corneal epithelia had significantly decreased mucin expression (Muc1 and Muc4, P=0.0043) and increased interferon-γ production (P=0.0303). Awat2 KO globes have a significantly shortened time of droplet adherence to their ocular surface (P=0.0053), indicating a decreased tear film adherence capacity. Wildtype corneal epithelia does not express Awat2, indicating that the EDED phenotype is secondary to the loss of Awat2 from the meibomian glands. ConclusionsAwat2 KO mice recapitulate many of features of human MGD and EDED, representing a model to test novel therapeutics.

The Long-Term Effect of Kidney Transplantation on the Serum Fatty Acid Profile

Background: Epidemiologic evidence has demonstrated the prevalence of metabolic disorders and increased cardiovascular risk related to lipid metabolism disorders in kidney transplant recipients. Therefore, it is of great importance to understand lipid alterations and to look for ways to reduce cardiovascular risk in this patient group. Methods: Our study included 25 patients with chronic kidney disease undergoing kidney transplantation (KTx). Three blood samples were taken from each patient: before KTx, 3 months after KTx and 6–12 months after KTx. A series of biochemical blood tests and a detailed analysis of the serum fatty acid profile were performed. Results: In our previous study, the effects of kidney transplantation on serum fatty acid (FA) profile 3 months after the procedure were investigated. The current study shows the longer-term (6–12 months) effects of the procedure on the serum FA profile. We found that although n-3 polyunsaturated FA levels started to decrease 3 months after surgery, they normalized over a longer period of time (6–12 months). Furthermore, we observed a strong decrease in ultra-long-chain FAs and an increase in odd-chain FAs over a longer time after kidney transplantation. All of the above FAs may have an important impact on human health, including inflammation, cardiovascular risk or cancer risk. Conclusions: The changes in serum FA profiles after kidney transplantation are a dynamic process and that more detailed studies could provide an accurate indication for supplementation with some FAs or diet modification.

An economically viable stable isotope-enhanced multiple reaction monitoring method for total fatty acid analysis in a mouse model of non-alcoholic fatty liver disease

The complex pathological mechanisms of non-alcoholic fatty liver disease (NAFLD) are closely related to dysregulated lipid metabolism, and the therapeutic effects of the traditional Chinese medicine Zexie-Baizhu Decoction (AA) on NAFLD have been gaining increasing attention. However, research into altered lipid metabolism, especially fatty acids, in NAFLD and the intervention of AA faces technical challenges, especially in the precise quantitative analysis of fatty acids in biological samples. The high complexity of biological matrices, particularly after drug intervention, greatly increases the difficulty of detection. Therefore, this study innovatively developed a simple and economical stable isotope derivatization technique by synthesizing d6N,N-dimethylethylenediamine (d6-DMED) in the laboratory, establishing a simple and economical method for fatty acid quantification. This method employs a chemical reaction under low-temperature conditions to ensure the efficient synthesis of d6-DMED. Using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry technique (UHPLC-MS/MS), combined with optimized chromatographic separation conditions and dynamic multiple reaction monitoring mode, the study established a highly sensitive detection method for 35 fatty acid derivatives. Methodological evaluation showed that the limits of quantification ranged from 0.002 to 0.060 μM, with high linearity of R² > 0.995. Additionally, the relative recovery rates were between 93.14% and 106.63%. To further demonstrate the feasibility of this method for fatty acid quantification, it was applied to measure fatty acids in multiple tissues in a mouse NAFLD model, as well as the effects of AA intervention on fatty acid metabolism. This rapid, simple, and cost-effective detection method not only enhances the understanding of NAFLD mechanisms but also provides a new strategy for evaluating the biological complex system after drug intervention.

The unique metabolic and lipid profiles of patients with severe COVID-19 compared to severe community-acquired pneumonia: a potential prognostic and therapeutic target

ABSTRACT Background Compare the changes and differences in metabolome and lipidome profiles among severe COVID-19 and CAP patients with ARF to identify biomarkers that could be used for personalized diagnosis, prognosis, and treatment. Research design and methods Plasma samples were taken at hospital admission (baseline) and on the 5th day of hospitalization (follow-up) and examined by RP-LC-QTOF-MS and HILIC-LC-QTOF-MS. Results 127 patients, 17 with CAP and 110 with COVID-19, were included. The analysis revealed 87 altered metabolites, suggesting changes in the metabolism of arachidonic acid, glycerolipids, glycerophospholipids, linoleic acid, pyruvate, glycolysis, among others. Most of these metabolites are involved in inflammatory, hypoxic, and thrombotic processes. At baseline, the greatest differences were found in phosphatidylcholine (PC) 31:4 (p < 0.001), phosphoserine (PS) 34:3 (p < 0.001), and phosphatidylcholine (PC) 36:5 (p < 0.001), all of which were notably decreased in COVID-19 patients. At follow-up, the most dysregulated metabolites were monomethyl-phosphatidylethanolamine (PE-Nme) 40:5 (p < 0.001) and phosphatidylcholine (PC) 38:4 (p < 0.001). Conclusions Metabolic and lipidic alterations suggest inhibition of innate anti-inflammatory and anti-thrombotic mechanisms in COVID-19 patients, which might lead to increased viral proliferation, uncontrolled inflammation, and thrombi formation. Results provide novel targets for predictive biomarkers against CAP and COVID-19. Trial registration Not applicable.