Tissue Lipid Research Articles

Utilizing mechatronic agilent gas chromatography to validate therapeutic efficacy of Combretum paniculatum against oxidative stress and inflammation

The quest for novel antioxidant and anti-inflammatory medications from medicinal plants is crucial since the plants contain bioactive compounds with a better efficacy and safety profile than orthodox therapy. This study harnesses the capabilities of mechatronics-driven Agilent Gas Chromatography, deploying in vitro, in vivo, and in silico models to unravel the antioxidant and anti-inflammatory attributes within Combretum paniculatum ethanol extract (CPEE). Employing gas chromatography-mass spectroscopy (GC-MS), our analysis efficiently segregates and evaluates volatile compound mixtures, a technique renowned for identifying organic compounds, as exemplified by its success in detecting fatty acids in food and resin acids in water. Using gas chromatography-mass spectrometry (GC-MS) and GC-FID analyses, this paper ascertains the comprehensive phytochemical composition of CPEE. Also, Molecular interactions of identified compounds with cyclooxygenase (COX-2) implicated in inflammatory urpsurge is verified. GC-MS and GC-FID analyses unveil 41 phytoconstituents within CPEE. Based on the in vitro research, CPEE demonstrated potential in inhibiting thiobarbituric acid-reactive substances, nitric oxide, and phospholipase lipase A2 with inhibition rates of 2.284, 6.547, and 66.8 μg/mL respectively. In vivo experiments confirm CPEE's efficacy in inhibiting granuloma tissue formation, lipid peroxidation, and neutrophil counts compared to untreated rats. Moreover, CPEE elicited a significant (P < 0.05) increase in the activities of SOD, CAT, and GSH concentrations while decreasing C-reactive protein, signifying promising therapeutic potential. Highlighting interactions between top-scoring phytoligands (epicatechin, catechin, and kaempferol) and COX-2, the findings underscore their drug-like characteristics, favorable pharmacokinetics, and enhanced safety toxicity profiles. Results from in vitro, in vivo, and in silico studies, highlights CPEE remarkable antioxidant and anti-inflammatory potentials.

Monotropein mitigates methotrexate-induced liver injury by activating autophagy and inhibiting ferroptosis

Methotrexate (MTX) is effective for the therapy of cancer, lupus erythematosus, rheumatoid arthritis, psoriasis and other diseases. However, the hepatotoxicity of MTX often leads to withdrawal and discontinuation of drugs, and then limits its clinical application. Monotropein (MON), an iridoid glycosides distributing in many edible and medicinal plants, has been exhibited to prevent liver and kedney injury induced by chemicals and related diseases. The current study aimed to assess the potential beneficial effects of MON in mitigating MTX-induced liver injury together with delineating the implicated mechanisms. A MTX-induced liver injury model in mice and BRL 3A cells were developed to explore the hepatoprotection of MON. GEO and WGCNA analysis were conducted to predict the possible mechanism of MTX on liver injury. The results demonstrated that MON can decrease the serum levels of AST and ALT, increase the activities of antioxidant SOD and GSH, and improve the morphological alteration of liver tissue, and reduce the accumulation of lipids in hepatocytes and liver tissue of mice treated with MTX. Moreover, our results also exhibited that MON can activate autophagy as assessed by autophagosome formation, expression of protein related with autophagy, and inhibit ferroptosis as evaluated by mitochondrial integrity, Fe2+level and key protein expression changes, and CQ (inhibitor of autophagy) and RSL-3 (the activator of ferroptosis) reversed the effects of MON on autophagy and ferroptosis of hepatocytes injured by MTX. Therefore, MON attenuates liver injury of MTX by activating autophagy and inhibiting ferroptosis. These findings provide new insights into MON as a potential healthy ingredient in functional food.

GA receptor targeted chitosan oligosaccharide polymer nanoparticles improve non-alcoholic fatty liver disease by inhibiting ferroptosis

Excessive iron in the liver may exacerbate Non-alcoholic fatty liver disease (NAFLD) by increasing the risk of liver cell expansion, inflammation and fibrosis. Ferroptosis in liver cells may lead the progression of simple fatty liver degeneration to steatohepatitis (NASH). More and more studies shew that ferroptosis played a crucial role in the pathological process of NAFLD. Based on the mechanism of ferroptosis, this study first synthesized a liver targeted 18-β-Glycyrrhetinic-acid-chitosan oligosaccharide -N-acetylcysteine polymer (GCNp), and further curcumin (Cur) was used as model drug to prepare Cur loaded nanodelivery system (GCNp-Cur NPs). The particle size of GCNp-Cur NPs was 132.5 ± 9.8 nm, PDI was 0.148 ± 0.026 and the potential was 23.8 mV. GCNp-Cur NPs can regulate the GPX4/GSH pathway, inhibit lipid peroxidation, restore cellular oxidative environment, reduce free Fe2+, improve cellular lipid metabolism and iron metabolism, thereby NPs inhibited liver cell ferroptosis through multiple pathways. Additionally, GCNp-Cur NPs could also alleviate liver tissue lipid accumulation and oxidative damage, delaying disease progression, and providing a new method and theoretical basis for the treatment of NAFLD.

Dietary Milk Phospholipids Increase Body Fat and Modulate Gut Permeability, Systemic Inflammation, and Lipid Metabolism in Mice

The study aimed at how dietary milk polar lipids affect gut permeability, systemic inflammation, and lipid metabolism during diet-induced obesity (DIO). C57BL/6J mice (n = 6x3) were fed diets with 34% fat as energy for 15 weeks: (1) modified AIN-93G diet (CO); (2) CO with milk gangliosides (GG); (3) CO with milk phospholipids (MPL). Gut permeability was assessed by FITC-dextran and sugar absorption tests. Intestinal tight junction proteins were evaluated by Western blot. Plasma cytokines were measured by immunoassay. Body composition was assessed by magnetic resonance imaging. Tissue lipid profiles were obtained by thin layer chromatography. Hepatic expression of genes associated with lipid metabolism was assessed by RT-qPCR. MPL increased the efficiency of converting food into body fat and facilitated body fat accumulation compared with CO. MPL and GG did not affect fasting glucose or HOMA-IR during DIO. MPL increased while GG decreased plasma TG compared with CO. MPL decreased phospholipids subclasses in the muscle while increased those in the liver compared with CO. GG and MPL had little effect on hepatic expression of genes associated with lipid metabolism. Compared with CO, MPL decreased polar lipids content in colon mucosa. Small intestinal permeability decreased while colon permeability increased and then recovered during the feeding period. High-fat feeding increased plasma endotoxin after DIO but did not affect plasma cytokines. MPL and GG did not affect plasma endotoxin, adipokines and inflammatory cytokines. After the establishment of obesity, MPL increased gut permeability to large molecules but decreased intestinal absorption of small molecules while GG tended to have the opposite effects. MPL and GG decreased mannitol and sucralose excretions, which peaked at d 45 in the CO group. MPL decreased occludin in jejunum mucosa compared with CO. GG and MPL did not affect zonula occludens-1 in gut mucosa. In conclusion, during DIO, milk GG decreased gut permeability, and had little effect on systemic inflammation and lipid metabolism; MPL facilitated body fat accumulation, decreased gut permeability, did not affect systemic inflammation.

Биохимические показатели мышц судака из Рыбинского водохранилища и оценка риска их потребления

Fish, as a food component, is very beneficial for human health. It is rich in protein, valuable fatty acids, vitamins and minerals. However, when consuming it, there is a risk of toxic substances entering the human body that ac-cumulate in the tissues of aquatic organisms, for example, heavy metals. The purpose of the work is to determine the biochemical parameters in the muscles of pike perch from the reaches of the Rybinsk reservoir, which differ in anthropogenic load, and to assess the risks of human consumption of this species. The amount of water, dry matter, lipids, protein, minerals and carbohydrates in muscle tissue was determined using standard methods. To assess the threat to human health associated with the potential duration of exposure to heavy metals from walleye consumption, target and cumulative hazard ratios were calculated. The assessment of carcinogenic risk to human health was determined using the target and general cancer risk index. Calculated indicators were obtained based on data on the content of heavy metals in the muscles of pike perch, established earlier. In the muscles of pike perch specimens from the Sheksninsky and Volzhsky reaches, no significant differences between biochemical parameters were found. According to the ratio of protein and lipids in muscle tissue, the studied individuals belong to category A, and according to the amount of lipids – to fish with a low-fat content. The estimated dietary intakes for weekly intakes of heavy metals from pike perch meat was below the reference values. The target and total hazard coefficient turned out to be less than one, which indicates that there is no potential non-carcinogenic risk for humans when consuming pike perch meat. The target cancer risk indices for Cd, Pb, Al and Cr are within acceptable ranges. The total risk of developing cancer for these metals is more than 1 in 100,000.

Characteristics of the Fatty Acid Composition of the Vacuolar Membrane Lipids Under the Conditions of Stress Induced by Copper Ions

The effect of different concentrations of copper ions (100 and 500 µM) on the fatty acid composition of the vacuolar membrane lipids of beet root tissues (Beta vulgaris L.) was studied. Exposure to 100 μM copper led to an increase in the content of FAs by 57 μg/mg of total lipids as compared to the control. Stearoyl desaturase (SDR) activity decreased from 0.87 in the control to 0.77 at 100 μM copper. Exposure to 500 μM copper caused an increase in the SDR activity up to 0.93, but the proportion of FAs decreased by 50 μg/mg of total lipids compared with 100 μM copper. In addition, there was an increase in the saturation of tonoplast lipids to 44 and 40% at 100 and 500 μM Cu²⁺, respectively. The results suggest that FAs of tonoplast lipids are involved in the stress response mechanisms induced by excessive Cu²⁺ concentrations.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery.

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1-9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.

Deceased donor kidney function and branched chain amino acid metabolism during ex vivo normothermic perfusion

Current kidney perfusion protocols are not optimized for addressing the ex vivo physiological and metabolic needs of the kidney. Ex vivo normothermic perfusion may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. Here, we assessed the association of tissue metabolic changes with changes in a kidney injury biomarker and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12- hour ex vivo normothermic perfusion. The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean age of the deceased kidney donors was 43 years with an average cold ischemia time of 37 hours. Urine output and creatinine clearance progressively increased and peaked at six hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% confidence interval 1.5, 140) urinary neutrophil gelatinase-associated lipocalin at six hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branched chain amino acid metabolism and that their tissue levels negatively correlated with urine output among all kidneys at six hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Thus, we showed that six hours is needed for kidney function recovery during ex vivo normothermic perfusion and that branched chain amino acid metabolism may be a major determinant of organ function and resilience.

CYB5R3 overexpression exhibits sexual dimorphism: Mitochondrial and metabolic adaptations in transgenic female mice during calorie restriction

There is a pressing need to develop new strategies for enhancing health in the elderly and preventing the rise in age-related diseases. Calorie restriction without malnutrition (CR) stands among the different antiaging interventions. Lifelong CR leads to increased expression and activity of plasma membrane CYB5R3, and male mice overexpressing CYB5R3 exhibit some beneficial adaptations that are also seen with CR. However, the mechanisms involved in both interventions could be independent since key aspects of energy metabolism and tissue lipid profile do not coincide, and many of the changes induced by CR in mitochondrial abundance and dynamics in the liver and skeletal muscle could be counteracted by CYB5R3 overexpression. In this study, we sought to elucidate the impact of CR on key markers of metabolic status, mitochondrial function, and pro-oxidant/antioxidant balance in transgenic (TG) female mice overexpressing CYB5R3 compared to their WT littermates. In females fed ad libitum, CYB5R3 overexpression decreased fat mass, led to a preferred utilization of fatty acids as an energy source, upregulated key antioxidant enzymes, and boosted respiration both in skeletal muscle and liver mitochondria, supporting that CYB5R3 overexpression is phenotypic closer to CR in females than in males. Whereas some markers of mitochondrial biogenesis and dynamics were found decreased in TG females on CR, as also found for the levels of Estrogen Receptor α, mitochondrial abundance and activity were maintained both in skeletal muscle and in liver. Our results reveal overlapping metabolic adaptations resulting from the overexpression of CYB5R3 and CR in females, but a specific crosstalk occurs when both interventions are combined, differing from the adaptations observed in TG males.

The effects of high-intensity interval training/moderate-intensity continuous training on the inhibition of fat accumulation in rats fed a high-fat diet during training and detraining

BackgroundCompared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet.MethodsAfter being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting.ResultsHIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression.ConclusionsHIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation.Graphical

Complex actions of sodium glucose transporter-2 inhibitors on lipids, calcific atherosclerosis, and bone density.

Inhibitors of sodium-glucose cotransporter-2 (SGLT2) lower renal glucose reabsorption and, thus, are used to treat patients with type 2 diabetes mellitus. Clinical trials coincidentally showed that SGLT2 inhibitors also benefitted patients with heart failure. This review explores the impact of SGLT2 inhibitors on other aspects of cardiovascular disease and skeletal health. In some, but not all, clinical and preclinical studies, SGLT2 inhibitors are found to reduce serum levels of free fatty acids and triglycerides. Their effects on total and low-density lipoprotein cholesterol and cardiac function also vary. However, SGLT2 inhibitors reduce lipid accumulation in the liver, kidney, and heart, and alter expression of lipid metabolism genes. Effects on free fatty acid uptake in abdominal fat depots depend on the location of adipose tissue. In male, but not female, mice, SGLT2 inhibitors reduce the atherosclerotic lesions and aortic calcium deposition. With respect to skeletal health, recent literature has reported conflicting associations with the risks of fracture and amputation. Studies suggest that SGLT2 inhibitors reduce tissue lipid accumulation, and in a sex-dependent manner, atherosclerosis and vascular calcification. However, their effects on lipid levels and bone health are complex and remain to be established.

SIRT3/AMPK Signaling Pathway Regulates Lipid Metabolism and Improves Vulnerability to Atrial Fibrillation in Dahl Salt-Sensitive Rats.

Hypertension may result in atrial fibrillation (AF) and lipid metabolism disorders. The Sirtuins3 (SIRT3)/AMP-activated protein kinase (AMPK) signaling pathway has the capacity to regulate lipid metabolism disorders and the onset of AF. We hypothesize that the SIRT3/AMPK signaling pathway suppresses lipid metabolism disorders, thereby mitigating salt-sensitive hypertension (SSHT)-induced susceptibility to AF. The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). Then DSH group was administered either oral metformin (MET, an AMPK agonist) or intraperitoneal injection of Honokiol (HK, a SIRT3 agonist). This experimental model allowed for the measurement of Systolic blood pressure (SBP), the expression levels of lipid metabolism-related biomarkers, pathological examination of atrial fibrosis, and lipid accumulation, as well as AF inducibility and AF duration. DSH decrease SIRT3, phosphorylation-AMPK, and very long-chain acyl-CoA dehydrogenase, (VLCAD) expression, increased FASN and FABP4 expression and concentrations of free fatty acid and triglyceride, atrial fibrosis and lipid accumulation in atrial tissue, enhanced level of SBP, promoted AF induction rate and prolonged AF duration, which are blocked by MET and HK. Our results also showed that the degree of atrial fibrosis was negatively correlated with VLCAD expression, but positively correlated with the expression of FASN and FABP4. We have confirmed that a high-salt diet can result in hypertension, and associated atrial tissue lipid metabolism dysfunction. This condition is linked to the inhibition of the SIRT3/AMPK signaling pathway, which plays a significant role in the progression of susceptibility to AF in SSHT rats.

Regulation of MicroRNAs After Spinal Cord Injury in Adult Zebrafish.

Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI.

Assessment of Amphibola crenata as a bioindicator of estuarine trace element pollution using biochemical and physiological endpoints

To assess its utility as a bioindicator of estuarine contamination, Amphibola crenata, a pulmonate mud snail, was collected from 17 estuaries in New Zealand. Whole-body soft tissue trace element concentrations were measured via quadrupole inductively coupled plasma mass spectrophotometer (Q-ICP-MS) and were found to be significantly positively correlated with sediment trace element profiles for arsenic, copper and lead. Snails from polluted estuaries generally displayed higher ammonia excretion rates, elevated whole-body soft tissue catalase activity and lipid peroxidation compared to snails from reference sites. Across all sites haemolymph glucose was positively correlated with the tissue burdens of arsenic, copper, nickel and zinc, while haemolymph protein was negatively correlated with arsenic, cadmium and zinc soft tissue concentrations, indicative of altered energy metabolism associated with trace element contamination. Overall, sites were distinguishable by application of the array of measures employed. Our findings suggest that gastropods have significant value as bioindicators of estuarine health.

Hepatoprotective Effects of Aqueous Extract of Perilla fructescens against Alcohol-Induced Liver Injury in Mice

Excessive alcohol intake leads to significant physiological complications, particularly alcoholic liver diseases (ALD). The extent of liver damage caused by ethanol correlates with increased oxidative stress and accumulation of lipids in the hepatic tissue. In this study, we investigated the defense properties of the aqueous extract of Perilla frutescens Briton Var. acuta Kudo (PF) on hepatic injury in chronically ethanol-treated mice. The mice were orally administered the water extract from PF for 4 weeks with ethanol treatment (3 g/kg. P.O.). The level of malondialdehyde (MDA) in the liver tissues was determined. A substantial increase in MDA generation was detected in the livers of mice subjected to ethanol exposure, whereas the administration of PF markedly reduced MDA levels in hepatic tissues. Additionally, histological analysis of the liver tissue was performed. Histopathological investigation revealed a significant reduction in hepatocellular necrosis in the PF-treated group. This study demonstrated that the aqueous extract of Perilla frutescens Briton Var. acuta Kudo (PF) attenuated chronic ethanol-induced liver injury by augmenting the antioxidant capacity of mice. These results can be utilized for the development of high-value-added products using PF.

Tangzhiping Decoction Improves Glucose and Lipid Metabolism and Exerts Protective Effects Against White Adipose Tissue Dysfunction in Prediabetic Mice.

Prediabetes, characterized by a series of metabolic abnormalities, increases the risk of diabetes and cardiovascular diseases. Tangzhiping (TZP), a clinically validated traditional Chinese medicine formula, is used to treat impaired glucose tolerance. However, the underlying mechanism of TZP in intervening prediabetes is not fully elucidated. The current study aimed to evaluate the protective effect of TZP against prediabetes mice and explore its potential mechanism. After establishing a prediabetic animal model through 12 weeks of high-fat diet (HFD) feeding, mice were subjected to TZP for 8 weeks. Various parameters related to body weight, glucose and lipid metabolism, and insulin sensitivity were measured. Histopathological examinations observed adipose cell size and liver lipid deposition. The Sable Promethion system assessed energy metabolism activity. Transcriptomic analysis of Epididymal white adipose tissue (EWAT) identified enriched pathways and genes. The key genes in the enriched pathways were identified through RT-PCR. Our data revealed that the administration of TZP reduced body weight and fat mass in a prediabetes mouse model. TZP normalized the glucose and insulin levels, improved insulin resistance, and decreased plasma TC and FFA. The alleviation of adipose tissue hypertrophy and lipid deposition by TZP was demonstrated through pathological examination. Indirect calorimetry measurements indicated a potential increase in VO2 and EE levels with TZP. The results of EWAT transcription showed that TZP reversed pathways and genes related to inflammation and catabolic metabolism. RT-PCR demonstrated that the mRNA expression of inflammation and lipolysis, including Tlr2, Ccr5, Ccl9, Itgb2, Lipe, Pnpla2, Cdo1, Ces1d, Echs1, and Acad11, were changed by TZP treatment. TZP effectively alleviates obesity, impaired glucose and lipid metabolism, and insulin resistance. The effect of TZP might be associated with the regulation of gene expression in dysfunctional adipose tissue.

Expression of concern: “Curcumin and linseed oil co-delivered in phospholipid nanoemulsions enhances the levels of docosahexaenoic acid in serum and tissue lipids of rats”

Expression of concern: “Curcumin and linseed oil co-delivered in phospholipid nanoemulsions enhances the levels of docosahexaenoic acid in serum and tissue lipids of rats”

N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats.

Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS. The results of different studies over the past decades have established the protective effect of NAE on many pathological conditions. This study aimed to investigate the cardioprotective effects of C18:0 NAE- N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE- N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues. The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis. The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes. The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.

Structural characterization of sphingomyelins from tissue using electron-induced dissociation.

Sphingomyelins (SMs) and resulting metabolic products serve important functional and cell signaling roles and can act as potential biomarkers and therapeutic targets in many pathological disorders. SMs each contain a sphingoid base, an amide-linked fatty acyl chain, and a phosphocholine headgroup. Despite these simple building blocks, variations and modifications of both the sphingoid base and the fatty acyl chain result in a diverse array of structurally complicated SM compounds. Conventional tandem mass spectrometry (MS/MS) using the collision-induced dissociation (CID) method only provides limited structural information, necessitating other tools to unravel the structural complexity of these lipids. We utilize electron-induced dissociation (EID) and sequential CID/EID approaches to elucidate detailed structural features of SMs. Integrating the CID/EID method into an imaging MS workflow enables accurate identification of SMs directly from kidney tissue. The application of EID enables identification of SMs at the molecular species level, identifying the sphingosine base and the amide-linked fatty acyl chains. Furthermore, removal of the phosphocholine headgroup via CID followed by sequential EID in an MS3 analysis (CID/EID) enhances the structural information obtained. CID/EID provides diagnostic fragmentation patterns revealing the hydroxylation site and double bond position in both the sphingosine base and amide-linked fatty acyl chains. Detailed structural information of SMs from synthetic standards and biological tissue samples is obtained using an alternative electron-based dissociation method. Accurate characterization of SMs promises to better inform studies of tissue biochemistry, lipid metabolism, and molecular pathology.

Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity

BackgroundDiabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation. MethodsA comprehensive lipidomic analysis of different lipid groups, were performed on liver tissue and plasma samples obtained at the time of histology from a well-defined cohort of 72 MASLD participants. The lipid profiles of controls were compared to those of MASLD patients with obesity, diabetes, or a combination of both. ResultsMASLD patients without obesity or diabetes exhibited distinct changes in the lipid profile of their liver tissue. The presence of diabetes or obesity further modified these lipid profiles (e.g., ceramide 47:7;4O), with positive or negative correlation (p < 0.05). A step-wise increase (long-chain fatty acids, triglycerides, and ceramides) or decrease (ultra-long fatty acids, diglycerides, and phospholipids) for lipid groups was observed compared to control among patients with MASLD without obesity or diabetes to MASLD patients with obesity as a single risk factor, and MASLD patients with obesity and diabetes. Changes in lipids observed in the plasma did not align with their corresponding liver tissue findings. ConclusionThe changes observed in the composition of lipids are not similar in patients with obesity and diabetes among those with MASLD. This highlights the different metabolic processes at play. The presence of obesity or diabetes in patients with MASLD exacerbates these lipid derangements, underscoring the potential for targeted intervention in MASLD patients.