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Transcription profiling in the liver of undernourished male rat offspring reveals altered lipid metabolism pathways and predisposition to hepatic steatosis.

Clinical and animal studies have reported an association between low birth weight and the development of nonalcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in the rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose tissue, especially on a high-fat (HF) diet. Here, using microarray-based expression profiling combined with metabolic, endocrine, biochemical, histological, and lipidomic approaches, we assessed whether FR30 procedure sensitizes adult male offspring

Empagliflozin reduces the levels of CD36 and cardiotoxic lipids while improving autophagy in the hearts of Zucker diabetic fatty rats.

The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial made evident the potentiality of pharmacological sodium-glucose cotransporter 2 (SGLT2) inhibition for treating patients with diabetes and cardiovascular disease. Since the effect of empagliflozin or other SGLT2 inhibitors on the whole cardiac metabolic profile was never analysed before, and with the purpose to contribute to elucidate the benefits at cardiac level of the use of empagliflozin, we explored the effect of the treatment with empagliflozin for six weeks on

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unr

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… Modern methods of lipidomics and metabolomics allow us to study such changes in detail [ 22 , 23 , 24 , 25 , 26 ]. … Statistical Analysis Prior to statistical analysis, metabolomic and lipidomic data were subjected to preprocessing as follows. …

A simple and reproducible method for quantification of human tear lipids with ultrahigh-performance liquid chromatography-mass spectrometry.

PURPOSE: The purpose was to select a simple and reproducible method for lipid measurements of human tears with ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS). Two sample preparation procedures were evaluated and compared: the Bligh and Dyer (BD) liquid-liquid extraction method with chloroform and methanol and protein precipitation with isopropanol (IPA). METHODS: Reproducibility and recovery efficiencies of 20 non-endogenous internal lipid standards were tested in 10-µl tear samples from healthy subjects. The lipid coverage and the simplicity of execution were also a

Cyclooxygenase 2 inhibition slows disease progression and improves the altered renal lipid mediator profile in the Pkd2WS25/- mouse model of autosomal dominant polycystic kidney disease.

BACKGROUND: Increased levels of cyclooxygenase (COX) derived oxylipins is the earliest and most consistent alteration in the renal oxylipin profile in diverse models of cystic kidney diseases. Therefore, we examined whether a COX2 inhibitor would reduce disease progression in the Pkd2WS25/- mouse model of autosomal dominant polycystic kidney disease (ADPKD). METHODS: Weanling normal and diseased male Pkd2 mice were provided diets that provided 0 or 50 mg celecoxib/kg body weight/day, for 13 weeks. Renal disease and function were assessed by histomorphometric analysis of renal cysts and measur

Rapid discrimination of pediatric brain tumors by mass spectrometry imaging.

PURPOSE: Medulloblastoma, the most common primary pediatric malignant brain tumor, originates in the posterior fossa of the brain. Pineoblastoma, which originates within the pineal gland, is a rarer malignancy that also presents in the pediatric population. Medulloblastoma and pineoblastoma exhibit overlapping clinical features and have similar histopathological characteristics. Histopathological similarities confound rapid diagnoses of these two tumor types. We have conducted a pilot feasibility study analyzing the molecular profile of archived frozen human tumor specimens using mass spectrom

Seasonal Alterations in Organic Phosphorus Metabolism Drive the Phosphorus Economy of Annual Growth in F. sylvatica Trees on P-Impoverished Soil.

Phosphorus (P) is one of the most important macronutrients limiting plant growth and development, particularly in forest ecosystems such as temperate beech (Fagus sylvatica) forests in Central Europe. Efficient tree internal P cycling during annual growth is an important strategy of beech trees to adapt to low soil-P. Organic P (Porg) is thought to play a decisive role in P cycling, but the significance of individual compounds and processes has not been elucidated. To identify processes and metabolites involved in P cycling of beech trees, polar-metabolome and lipidome profiling was performed

Hormone deprivation alters mitochondrial function and lipid profile in the hippocampus.

Mitochondrial dysfunction is a common hallmark in aging. In the female, reproductive senescence is characterized by loss of ovarian hormones, many of whose neuroprotective effects converge upon mitochondria. The functional integrity of mitochondria is dependent on membrane fatty acid and phospholipid composition, which are also affected during aging. The effect of long-term ovarian hormone deprivation upon mitochondrial function and its putative association with changes in mitochondrial membrane lipid profile in the hippocampus, an area primarily affected during aging and highly responsive to

Distinct oxylipin alterations in diverse models of cystic kidney diseases.

Cystic kidney diseases are characterized by multiple renal cysts and are the leading cause of inherited renal disease. Oxylipins are bioactive lipids derived from fatty acids formed via cyclooxygenase, lipoxygenase and cytochrome P450 activity, and are important regulators of renal health and disease. Oxylipins are altered in nephronophthisis, a type of cystic kidney disease. To further investigate and to determine whether other cystic renal diseases share these abnormalities, a targeted lipidomic analysis of renal oxylipins was performed in orthologous models of autosomal dominant polycystic

Beneficial Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients with Type 2 Diabetes Mellitus: Analysis of Responders and Non-Responders.

Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzy

Fatty acids profiling reveals potential candidate markers of semen quality.

Previous reports showed altered fatty acid content in subjects with altered sperm parameters compared to normozoospermic individuals. However, these studies focused on a limited number of fatty acids, included a short number of subjects and results varied widely. We conducted a case-control study involving 155 patients allocated into four groups, including normozoospermia (n = 33), oligoasthenoteratozoospermia (n = 32), asthenozoospermia (n = 25), and varicocoele (n = 44). Fatty acid profiling, including 30 species, was analyzed by a validated gas chromatography (GC) method on the whole semina

Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).

UNLABELLED: Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose trigly

High-resolution imaging mass spectrometry reveals detailed spatial distribution of phosphatidylinositols in human breast cancer.

High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is an emerging application for lipid research that provides a comprehensive and detailed spatial distribution of ionized molecules. Recent lipidomic approach has identified several phospholipids and phosphatidylinositols (PIs) are accumulated in breast cancer tissues and are therefore novel biomarker candidates. Because their distribution and significance remain unclear, we investigated the precise spatial distribution of PIs in human breast cancer tissues using high-resolution MALDI IMS. We evalu

Astrocyte-Associated ABCA1/APOE Responses Accompany Hippocampal Lipid Remodeling and Ectopic Neuronal Accumulation During Epileptogenesis.

Temporal lobe epilepsy (TLE) is characterized by progressive hippocampal remodeling, including reactive astrogliosis and aberrant neuronal positioning. Although lipid disturbances are implicated in epileptogenesis, how astrocyte-associated lipid responses relate to hippocampal remodeling remains poorly understood. Here, human TLE and kainic acid (KA)-treated mouse transcriptomic datasets identified ATP-binding cassette transporter A1 (ABCA1)/Abca1 as a nominal astrocyte-associated candidate, while KA- and pilocarpine-induced status epilepticus (SE) elicited astrocyte-associated ABCA1/apolipopr

Tongsai Granules Ameliorate Airway Mucus Hypersecretion in AECOPD by Remodeling LIPA-Driven Ceramide Metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongsai Granules (TSG) is a traditional Chinese medicine formula traditionally used for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm-heat obstructing lung syndrome, a condition characterized by cough, excessive sputum production, and dyspnea; however, its underlying therapeutic mechanisms remain unclear. AIM OF THE STUDY: To investigate the mechanisms by which TSG alleviates airway mucus hypersecretion in AECOPD through regulation of the LIPA/ceramide axis. MATERIALS AND METHODS: A murine AECOPD model and ai

DHA as a systems regulator of neuroinflammation: A narrative review integrating membrane organization, immunometabolism, and inflammatory resolution.

Neuroinflammation is a central feature of brain aging and a major driver of neurodegenerative and neuropsychiatric disorders. Conventional anti-inflammatory strategies have produced inconsistent clinical outcomes, reflecting the biological complexity of chronic neuroinflammation and the limited capacity of single-target interventions to modulate interconnected pathogenic pathways. This narrative review synthesizes evidence from mechanistic studies, clinical trials, and meta-analyses identified through structured searches of PubMed, Scopus, and Web of Science. Docosahexaenoic acid (DHA), the pr

KPB82 potently and selectively inhibits ACER2 and protects tumor and primary cells from doxorubicin-induced cytotoxicity.

Alkaline ceramidase 2 (ACER2) catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids, playing crucial roles in regulating various biological processes, including but not limited to cell proliferation, survival, and the DNA damage response. However, a pharmacological tool that regulates its catalytic and signaling functions remains to be developed. In this study, N-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]dodecane-1-sulfonamide (KPB82) was identified as a potent and selective ACER2 inhibitor. In vitro enzymatic assays showed that KPB82 inhibited ACER2 with an IC 50 of 190 nM,

CerS2 Overexpression Enhances Palmitoyl-CoA-Induced Cytotoxicity and Alters Ceramide Species Composition in Breast Cancer Cells.

Sphingolipid metabolism, particularly the balance between pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), has been associated with breast cancer progression. The aim of the present study was to examine whether ceramide synthase 2 (CerS2) overexpression is associated with changes in increased palmitoyl-CoA (PCA) based ceramide buildup and cell fate changes in MCF-7 breast cancer cells, a hormone receptor-positive model. CERS2 plasmid transfected cells were treated with PCA and/or the CerS inhibitor, fumonisin B1 (FB1). Cell viability, the proliferation marker proliferatin

Microplastics distinctly regulate cadmium accumulation and lipid homeostasis in maize: Mechanistic insights from membrane remodeling to gene expression.

Microplastics (MPs) derived from film mulching commonly exist in cadmium (Cd)-contaminated agricultural soil, but their impacts on Cd phytotoxicity are still controversial. Lipid remodeling is a key plant stress response, but whether conventional and biodegradable MPs differently regulate this process under Cd stress remain unclear. This study compared the effects of conventional polyethylene (PE) and biodegradable polylactic acid (PLA) MPs at two concentrations (0.1% and 1%) on Cd phytotoxicity in maize via a 35-day pot experiment, mainly focusing on the lipid homeostasis. Both individual and

Screening for high coronary plaque volume in primary prevention: integration of multi-omics and coronary calcium scoring into cardiovascular risk assessment.

BACKGROUND: Atherosclerotic plaque volume (PV) predicts future cardiovascular events. As coronary computed tomography angiography (CCTA) is unsuitable for population screening, individuals with high total (T)PV often remain undetected. OBJECTIVE: To evaluate the relative and incremental contributions of lipidomic risk score (LRS), polygenic risk score (PRS), and coronary artery calcium score (CAC) improves screening for high TPV. METHODS: Primary prevention participants in two trials underwent clinical assessment, CAC, and blood sampling for LRS and PRS. CCTA was obtained in participants wit