Search Results (56)

Background/Objectives: Altered lipid metabolism is a key feature of type 2 diabetes mellitus (T2DM), yet its impact on early spinal cord involvement remains poorly understood. Distinguishing between pathological lipid accumulation and adaptive metabolic responses is essential for interpreting initial stages of neural alteration in T2DM. This study aimed to characterize spinal cord lipid composition and ATPase activities in a rat model of T2DM. Methods: Zucker diabetic fatty (ZDF) rats were used as a model of T2DM and divided into diabetic and obese groups, with lean Zucker rats as controls. ATPase activities in spinal cord tissue were measured spectrophotometrically, and lipid profiling was performed using gas chromatography with flame-ionization detection. Indices of stearoyl-CoA desaturase-1 (SCD1) and delta-5 desaturase activity (D5D) were calculated from specific fatty acid ratios as estimates of enzyme-related activity. Results: Diabetic rats exhibited significantly higher levels of free monounsaturated fatty acids (MUFAs) compared with controls, while the obese group showed a moderate increase. Elevated SCD1 indices were indicative of increased estimated MUFA synthesis. Levels of free polyunsaturated fatty acids (PUFAs), including those crucial for myelin stability, as well as ATPase activities, remained unchanged, suggesting preserved basal membrane-associated enzyme function. Conclusions: This study identifies lipid alterations in the spinal cord preceding overt neurodegenerative changes in T2DM, characterized by increased free MUFA abundance, without evidence of altered ATPase activities. These findings support the interpretation that lipid changes observed at this stage are more consistent with adaptive metabolic remodeling than with overt structural or functional neural impairment. Full article

Obesity is among the top contributing factors for non-communicable chronic disease development and has attained menacing global proportions, affecting approximately one of eight adults. Phytochemicals that support energy metabolism and prevent obesity development have been the subject of intense research endeavors over the past several decades. Cycloastragenol is a natural triterpenoid compound and aglycon of astragaloside IV, known for activating telomerase and mitigating cellular aging. Here, we aim to characterize the effect of cycloastragenol on lipid metabolism in a glucose-induced obesity model in Caenorhabditis elegans. We assessed the changes in the body length, width, and area in C. elegans maintained under elevated glucose through automated WormLab system. Lipid accumulation in the presence of either cycloastragenol (100 μM) or orlistat (12 μM), used as a positive anti-obesity control drug, was quantified through Nile Red fluorescent staining. Furthermore, we evaluated the changes in key energy metabolism molecular players in GFP-reporter transgenic strains. Our results revealed that cycloastragenol treatment decreased mean body area and reduced lipid accumulation in the C. elegans glucose-induced model. The mechanistic data indicated that cycloastragenol suppresses the nuclear hormone receptor family member NHR-49 and the delta(9)-fatty-acid desaturase 7 (FAT-7) enzyme, and activates the 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AAK-2) and the protein skinhead 1 (SKN-1) signaling. Collectively, our findings highlight that cycloastragenol reprograms lipid metabolism by down-regulating the insulin-like receptor (daf-2)/phosphatidylinositol 3-kinase (age-1)/NHR-49 signaling while simultaneously enhancing the activity of the AAK-2/NAD-dependent protein deacetylase (SIR-2.1) pathway. The anti-obesogenic potential of cycloastragenol rationalizes further validation in the context of metabolic diseases and obesity management. Full article

Fatty acid desaturase 12 (FAD12) is a key enzyme in fatty acid biosynthesis, responsible for converting oleic acid to linoleic acid through desaturase activity. Euglena gracilis (Euglena) is an emerging platform for the industrial production of various metabolites, including lipids. However, a comprehensive understanding of Euglena’s fatty acid biosynthesis pathways remains incomplete, posing a significant barrier to the commercialization of Euglena bioproducts. To address this gap, we employed a bioinformatics approach to identify a Euglena gracilis FAD12 (Eg FAD12). We analyzed the evolutionary relationship of Eg FAD12 with its homologs from other organisms and revealed that the three canonical histidine box motifs are conserved among FAD12s. To characterize EgFAD12, we cloned it into the pEAQ-hyperstrans vector and overexpressed it in Nicotiana benthamiana to take advantage of its endogenous fatty acid pool, which could act as a substrate. The heterologous expression of FAD12 in N. benthamiana led to an increased linoleic acid content, demonstrating the suspected desaturase activity. To further confirm the function of Eg FAD12, we performed CRISPR-Cas9-mediated knockout of Eg FAD12 in Euglena, which resulted in a drastic reduction in linoleic acid (C18:2) without compromising biomass yield or lipid content. This work advances our understanding of fatty acid biosynthesis in Euglena and will aid in its adoption as a platform for producing customized lipids. Full article

Background: Obesity is a complex metabolic disease associated with several health complications, including insulin resistance, hypertension, and type 2 diabetes mellitus. Growing evidence indicates that fatty acid profiles and the activity of desaturating enzymes—stearoyl-CoA desaturase-1 (SCD1), delta-5 desaturase (D5D), and delta-6 desaturase (D6D)—are important factors in the pathophysiology of obesity. This review aims to summarise the current understanding of the alterations in lipid metabolism and desaturase activity in obesity, its complications, and potential therapeutic interventions. Methods: A literature review was performed using the PubMed, Scopus, and Web of Science databases. Systematic reviews, meta-analyses, clinical studies, cross-sectional studies, and animal studies that assessed fatty acid profiles and desaturase activity in the context of obesity were included. Results: Obesity is associated with significant changes in the profiles of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs), as well as altered desaturase activity. Increased activity of SCD1 and D6D and decreased activity of D5D are observed even in childhood and correlate with metabolic risk markers. Genetic variation in genes encoding fatty acid desaturases, such as fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and SCD1, influences lipid metabolism and susceptibility to metabolic disorders. Nutritional interventions, supplementation (e.g., omega-3 fatty acids, L-carnitine, and crocin), physical activity, and bariatric surgery positively influence the fatty acid profile and enzymatic activity, modifying the risk of obesity-related diseases. Conclusions: Fatty acid profile and desaturase activity are significantly altered in obesity and represent potential biomarkers and therapeutic targets for its treatment and the prevention of related complications. Their assessment may contribute to a more personalised approach to treating obesity and associated metabolic diseases. Full article

Background: Dyslipidemia and distorted fatty acid (FA) metabolism are frequent biochemical abnormalities associated with anorexia nervosa (AN). Gut microbiota is supposed to play an important role in the etiopathogenesis of AN. Apart from the digestive function of bile acids (BAs), these compounds have multiple metabolic functions due to the activation of specific receptors. Objective/aims: The aims of the study were to investigate biochemical measures, including plasma lipids (lipoproteins, respectively), fatty acid (FA) patterns, and the profile of plasma Bas, in AN patients and healthy controls (CON). Methods: Plasma phospholipid FA and BAs profiles were analyzed in 39 women with a restrictive type of AN (AN-R; median age 17 years) and in 35 CON women (median age 20 years). Results: Compared to CON, AN had an increased concentration of HDL-C, increased content of palmitic acid, and decreased proportion of linoleic acid. Moreover, AN had a drop in the level of the sum of PUFAn-6 and increased delta 9 desaturase activity for stearic acid. In AN, we found decreased levels of plasma tauroursodeoxycholic acid (TUDCA). In AN, concentrations of 22:5n-6, 16:0, 20:3n-6 and fat mass index were predic-tors of HDL-C levels (R² = 0.43). Conclusions: Patients with AN-R had an increased concentration of HDL-C, decreased levels of total PUFA n-6, and increased activity of D9D for stearic acid. Furthermore, AN exerted decreased levels of TUDCA. Therefore, a decreased level of TUDCA could potentially serve as a marker of AN. Full article

Background: Delirium is frequently observed in patients admitted to the intensive care unit, and is associated with mortality and morbidity. Although several studies have reported an association between polyunsaturated fatty acids (PUFAs) and cognitive disorders, the association between PUFA levels and development of delirium in patients with acute cardiovascular disease remains unknown. Objective: This study aimed to clarify the association between PUFA levels and development of delirium in the coronary intensive care unit (CICU). Methods: We enrolled 590 consecutive patients (mean age, 70 ± 14 years) admitted to the CICU of Juntendo University Hospital. Fasting serum PUFA levels were measured within 24 h of admission. Delta-5 desaturase activity was estimated as the ratio of arachidonic acid (AA) to dihomo-gamma-linolenic acid (DGLA). Furthermore, delirium was defined as patients having a delirium score of ≥4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was observed in 55 patients. DGLA levels were significantly lower, and delta-5 desaturase activity was significantly higher in patients with delirium than in those without delirium (both p < 0.001). Conversely, AA alone and omega-3 PUFAs did not differ between the groups. Additionally, DGLA and AA levels, but not omega-3 PUFA levels, were negatively associated; delta-5 desaturase activity was positively associated with the delirium score (both p < 0.001). The duration of delirium was significantly associated with DGLA and AA levels (p = 0.001 and p = 0.004, respectively). Moreover, multivariate analysis showed that decreased DGLA and increased delta-5 desaturase activity remained significant predictors of delirium. Conclusions: Low omega-6 PUFA levels and high delta-5 desaturase activity on admission were significantly associated with the development of delirium in the CICU, indicating that the evaluation of low omega-6 PUFA levels and related enzymes may identify patients at a high risk of developing delirium. Full article

10-Hydroxy-2-decenoic acid (10-HDA), a major fatty acid (FA) component of royal jelly, is synthesized in the mandibular glands (MGs) of worker honeybees. Despite its well-documented nutritional and therapeutic significance, the biosynthetic pathway and regulatory mechanisms of 10-HDA production remain largely unresolved. In this study, the molecular basis of 10-HDA biosynthesis and regulation in the MGs of newly emerged bees (NEBs), nurse bees (NBs), and forager bees (FBs) were investigated using RNA sequencing and weighted gene co-expression network analysis (WGCNA). A five-step biosynthetic pathway for 10-HDA was proposed, and cross-species analysis of Apis mellifera and A. cerana revealed the conserved expression patterns of 15 key enzymes involved. Functional validation via RNA interference (RNAi) demonstrated that knockdown of acyl-CoA Delta(11) desaturase (d11ds, LOC551527), a key enzyme in FA desaturation, led to a 50% reduction in 10-HDA levels. Protein–protein interaction (PPI) network analysis further identified transcriptional regulators Kay and Drep-2 as potential modulators of 10-HDA metabolism. This study provides the first comprehensive mechanistic model of 10-HDA biosynthesis in honeybee MGs and highlights the labor-specific regulation of FA metabolism. These findings offer promising genetic targets for improving the royal jelly quality through genetic technology. Full article

The SCD is a rate-limiting enzyme that catalyzes the synthesis of monounsaturated fatty acids (MUFAs) in dairy cows; however, its role in the mammary gland of buffalo is not well understood. In this study, we isolated and characterized the complete coding sequence (CDS) of the buffalo SCD gene from mammary gland tissue and investigated its effects on milk fat synthesis using bioinformatics analyses, tissue differential expression detection, and cellular functional experiments. The cloned SCD gene has a CDS length of 1080 bp, encoding a protein of 359 amino acids. This protein is hydrophilic, lacks a signal peptide, and contains four transmembrane domains, including 10 conserved motifs and a Delta9-FADS domain, characteristic of the fatty acid desaturase family involved in unsaturated fatty acid biosynthesis within the endoplasmic reticulum. Molecular characterization revealed that the physicochemical properties, conserved domains, structures, and functions of buffalo SCD are highly similar to those in other Bovidae species. Among the tissues analyzed, SCD expression was highest in the mammary gland during lactation and in the cerebellum during dry-off period. Notably, SCD expression in the mammary gland was significantly higher during lactation compared to the dry-off period. Subcellular localization experiments confirmed that SCD functions in the endoplasmic reticulum of buffalo mammary epithelial cells (BuMECs). Functional overexpression and interference experiments in BuMECs demonstrated that SCD promotes milk fat synthesis by affecting the expression of lipid synthesis-related genes such as ACACA, FASN, and DGAT1, as well as milk fat regulatory genes like SREBFs and PPARG, thereby influencing intracellular triglyceride (TAG) content. Additionally, 18 single-nucleotide polymorphisms (SNPs) were identified in the buffalo SCD gene, with a specific SNP at c.-605, showing potential as molecular markers for improving milk production traits. These findings highlight that the SCD gene is a key gene in buffalo milk fat synthesis, involved in the de novo synthesis of milk fatty acids. Full article

Transcriptomes from stem-inoculated Scots pine saplings were analyzed to identify unique and enriched H. annosum transcripts in the early stages of infection. Comparing different time points since inoculation identified 131 differentially expressed H. annosum genes with p-values of ≤0.01. Our research supports the results of previous studies on the Norway spruce–Heterobasidion annosum s.l. pathosystem, indicating the role of carbohydrate and lignin degradation genes in pathogenesis at different time points post-inoculation and the role of lipid metabolism genes (including but not limited to the delta-12 fatty acid desaturase gene previously reported to be an important factor). The results of this study indicate that the malic enzyme could be a potential gene of interest in the context of H. annosum virulence. During this study, difficulties related to incomplete reference material of the host plant species and a low proportion of H. annosum transcripts in the RNA pool were encountered. In addition, H. annosum transcripts are currently not well annotated. Improvements in sequencing technologies (including sequencing depth) or bioinformatics focusing on small subpopulations of RNA would be welcome. Full article

Introduction: Obesity is characterized by low-grade chronic inflammation, which can be modulated by lipid mediators derived from omega-3 (n-3) polyunsaturated fatty acids (PUFA). Obesity is a multifactorial disease, where genetic and environmental factors strongly interact to increase its development. In this context, the FADS1 gene encodes the delta-5 desaturase protein, which catalyzes the desaturation of PUFA. The rs174547 genetic variant of FADS1 has been associated with alterations in lipid metabolism, particularly with decreases in eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations. Objective: To analyze the effect of an n-3-supplemented diet on the fatty acid profile and composition in red blood cells (RBCs) of obese subjects carrying the rs174547 variant of the FADS1 gene. Methodology: Seventy-six subjects with obesity were divided into two groups: omega-3 (1.5 g of n-3/day) and placebo (1.5 g of sunflower oil/day). The dietary intervention consisted of a four-month follow-up. Anthropometric, biochemical, and dietary variables were evaluated monthly. The total fatty acid profile in RBC was determined using gas chromatography. The rs174547 variant was analyzed through allelic discrimination. Results: The n-3 index (O3I) increased at the end of the intervention in both groups. Subjects carrying the CC genotype showed significant differences (minor increase) in n-6, n-3, total PUFA, EPA, DHA, and the O3I in RBCs compared to TT genotype carriers in the n-3 group. Conclusions: The diet supplemented with EPA and DHA is ideal for providing the direct products that bypass the synthesis step affected by the FADS1 rs174547 variant in subjects carrying the CC genotype. The O3I confirmed an increase in n-3 fatty acids in RBCs at the end of the intervention. Full article

Adipose tissue plays an important role in pig production efficiency. Studies have shown that postnatal development has a vital impact on adipose tissue; however, the mechanisms behind pig adipose tissue early-life programming remain unknown. In this study, we analyzed the transcriptomes of the subcutaneous adipose tissue (SAT) of 1-day and 21-day old Laiwu piglets. The results showed that the SAT of Laiwu piglets significantly increased from 1-day to 21-day, and transcriptome analysis showed that there were 2352 and 2596 differentially expressed genes (DEGs) between 1-day and 21-day SAT in male and female piglets, respectively. Expression of genes in glycolysis, gluconeogenesis, and glycogen metabolism such as pyruvate kinase M1/2 (PKM), phosphoenolpyruvate carboxy kinase 1 (PCK1) and amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) were significantly different between 1-day and 21-day SAT. Genes in lipid uptake, synthesis and lipolysis such as lipase E (LIPE), acetyl-CoA carboxylase alpha (ACACA), Stearoyl-CoA desaturase (SCD), and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were also differentially expressed. Functional analysis showed enrichment of DEGs in transcriptional regulation, protein metabolism and cellular signal transduction. The protein–protein interaction (PPI) networks of these DEGs were analyzed and potential hub genes in these pathways were identified, such as transcriptional factors forkhead box O4 (FOXO4), CCAAT enhancer binding protein beta (CEBPB) and CCAAT enhancer binding protein delta (CEBPD), signal kinases BUB1 mitotic checkpoint serine/threonine kinase (BUB1) and cyclin-dependent kinase 1 (CDK1), and proteostasis-related factors ubiquitin conjugating enzyme E2 C (UBE2C) and cathepsin D (CTSD). Moreover, we further analyzed the transcriptomes of SAT between genders and the results showed that there were 54 and 72 DEGs in 1-day and 21-day old SAT, respectively. Genes such as KDM5D and KDM6C showed gender-specific expression in 1-day and 21-day SAT. These results showed the significant changes in SAT between 1-day and 21-day in male and female Laiwu pigs, which would provide information to comprehensively understand the programming of adipose tissue early development and to regulate adipose tissue function. Full article

Delta-12 fatty acid desaturases (FAD2s) actively regulate stress responses and cell differentiation in living organisms. In this study, six homologous FAD2 genes were identified based on the genome sequence of Lentinula edodes. Then, the six FAD2 protein sequences were analyzed using bioinformatics tools, including ExPASy ProtParam, SignalP, TMHMM, and TargetP. These analyses were performed to predict the physical and chemical properties, signal peptides, and transmembrane and conserved domains of these proteins. The polypeptide sequences were aligned, and a maximum likelihood phylogenetic tree was constructed using MEGA 7.0 software to elucidate the phylogenetic relationships between homologous FAD2 sequences. The results demonstrated that the FAD2 proteins contained three conserved histidine-rich regions (HXXXH, HXXHH, and HXXHH), which included eight histidine residues. The linoleic acid content and FAD2 enzyme activity were further analyzed, and the levels in the mutagenic heat-tolerant strain 18N44 were lower than those in the wild-type strain 18. Interestingly, the expression levels of the FAD2-2 and FAD2-3 genes under heat stress in strain 18N44 were lower than those in strain 18. These findings indicated that FAD2-2 and FAD2-3 may play major roles in the synthesis of linoleic acid during heat stress. Full article

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism. Full article

Background: The fatty acid profiles in cellular membranes can be influenced by many endogenic and external factors, including diet. They are also associated with numerous metabolic and health conditions, including cardiovascular diseases and inflammation. Objective: This study provides a comparative analysis of the fatty acid profiles in subjects on vegetarian and omnivorous diets. Methods: The study enrolled 152 apparently healthy subjects, comprising 78 omnivores and 74 individuals who had followed a vegetarian diet for a minimum of 2 years, including 61 vegans and 13 lacto-ovo vegetarians. The subjects in the omnivore and vegetarian groups were matched by gender, age, and body mass index (BMI). The composition of the fatty acids in their erythrocyte membranes was determined using gas–liquid chromatography and presented as a percentage of total fatty acids. Results: The study revealed statistically significant differences in the fatty acid profiles: vegetarians had higher levels of oleic acid (OA, 18:1 n-9) (p < 0.001) and linoleic acid (LA, 18:2 n-6) (p < 0.001), while at the same time having lower levels of gamma-linolenic acid (GLA, 18:3 n-6) (p < 0.05), eicosapentaenoic acid (EPA, 22:5 n-3) (p < 0.001), docosapentaenoic acid (DPA, 22:5 n-3) (p < 0.001), docosahexaenoic acid (DHA, 22:6 n-3) (p < 0.001), and total omega-3 polyunsaturated fatty acid (PUFA) (p < 0.001) and a lower omega-3 index (p < 0.001). Additionally, they had lower omega-3 to omega-6 PUFA (p < 0.001); EPA/arachidonic acid (ARA, 20:4 n-6) (p < 0.001); and DHA/ARA ratios (p < 0.001). The activity of delta-6 desaturases (D6D), estimated as the GLA/LA ratio, was higher in the omnivores (p < 0.005), while the activity of elongase 2 (ELOV2), estimated as the DPA/EPA ratio, was higher in the vegetarians (p < 0.005). Most of the differences presented in both vegans and vegetarians, except for GLA and D6D, where differences were observed only in vegans compared to omnivores. Discussion: This study highlights the distinct fatty acid profiles associated with vegan, lacto-ovo vegetarian, and omnivorous diets, suggesting their differential impact on inflammation, disease protection, and overall health. Understanding the implications of the fatty acid profiles within these dietary patterns can be used for personalized nutritional recommendations and supplementation for individuals adhering to specific dietary lifestyles. Full article

Background and objectives: Higenamine is an alkaloid found in different plant species like Aconitum japonica, Nandina domestica, Gnetum parvifolium, and Asarum heterotropoides. According to the available data in the literature, its dietary intake leads to an enhancement of lipolysis. The objective of this study was to explore whether the ingestion of a one-component higenamine supplement (75 mg/day) for three weeks would introduce some changes in the fatty acid (FA) profiles of serum phospholipids of female recreational athletes. Methods: A total of 12 female recreational athletes were included in a double-blind study, with six participants in both groups—a higenamine treatment group and placebo group. Serum phospholipids were isolated via one-dimensional thin-layer chromatography. Fatty acid methyl ester samples from the phospholipids were analyzed by a gas–liquid chromatography method. Desaturase and elongase activities were calculated from product/precursor FA ratios. Results: In the group that was undergoing higenamine treatment, a statistically significant increase in the levels of linolenic acid, a total n − 6 polyunsaturated FAs (PUFAs), and an n − 6/n − 3 FA ratio were observed. But saturated palmitic acid and monounsaturated palmitoleic and oleic acid, as well as consequent total saturated FAs and monounsaturated FA acids decreased in serum phospholipids. Also, after 3 weeks of higenamine supplementation, arachidonic n − 6 acid and docosapentaenoic n − 3 acids levels were significantly decreased, and estimated delta-5 desaturase activity (arachidonic/dihomo-gamma-linolenic acid ratio) was decreased too. In the placebo group, a significant change was increased levels of oleic acid compared to baseline levels. Conclusion: According to the results obtained for the FA status of serum phospholipids, treatment with higenamine was followed by a modulation of serum phospholipid FA profiles. Furthermore, this could influence the desaturation/elongation metabolic pathway of endogenous FA metabolisms, leading to a decrease in delta-5 desaturase activity and consequently lower levels of long-chain PUFAs. For further discussion, it is necessary to assess the dietary intake of study participants. Full article