Search Results (7,329)

Background/Objectives: Obesity-related insulin resistance leads to the development of type 2 diabetes mellitus (T2DM); however, the pathophysiology of these metabolic alterations remains incompletely understood. This study aimed to characterize the lipidomic alterations during obesity–insulin resistance–T2DM progression in a high-sugar diet (HSD) model. Methods: Fruit flies were fed either a standard diet (SD) or an HSD and monitored across a 14-day period. Metabolic phenotyping and lipidomic profiling were conducted during the experiment. Results: After two days of HSD, fruit flies exhibited an obesity phenotype (50% increase in triglyceride content) and insulin resistance (hyperglycemia and insulin overexpression), progressing to an early T2DM-like state (increased triglycerides, hyperglycemia, and normal insulin expression) from days 4 to 6, and finally to a late T2DM-like phenotype (increased triglycerides, hyperglycemia, and insulin down-regulation) from days 8 to 14. Multivariate analyses indicated an altered lipidome profile in HSD-fed fruit flies from day 2 until the end of the experiment. Fatty acids and phosphatidylethanolamines (PEs) containing 16:0, 16:1, and 18:1 acyl chains were significantly altered during the development of obesity-related insulin resistance and early T2DM-like state (days 2 to 6); whereas palmitic acid and oleic acid-LysoPE alterations were associated with the onset and progression of obesity-related T2DM-like state (days 4 to 14). Conclusions: The progression from obesity-related insulin resistance to a T2DM-like state in an HSD-fed D. melanogaster model is accompanied by distinct lipidomic signatures involving 16- and 18-carbon fatty acid derivatives. These findings provide insight into potential biomarkers and mechanistic pathways in the early pathogenesis of T2DM. Full article

The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut–heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research. Full article

Background: Acute pancreatitis (AP) is characterized by the abnormal activation of pancreatic enzymes due to various causes, leading to local pancreatic inflammation. This can trigger systemic inflammatory response syndrome and multi-organ dysfunction. Hyperlipidemia, mainly resulting from lipid metabolism disorders and elevated triglyceride levels, is a major etiological factor in AP. This study aims to investigate the role of lipid metabolism-related genes in the pathogenesis of AP and to propose novel strategies for its prevention and treatment. Methods: We obtained AP-related datasets GSE3644, GSE65146, and GSE121038 from the GEO database. Differentially expressed genes (DEGs) were identified using DEG analysis and gene set enrichment analysis (GSEA). To identify core lipid metabolism genes in AP, we performed least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis. Gene and protein interactions were predicted using GeneMANIA and AlphaFold. Finally, biomarker expression levels were quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) in an AP mouse model. Results: Seven lipid metabolism-related genes were identified as key biomarkers in AP: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee. The biological roles of these genes mainly involve fatty acid metabolism, cholesterol metabolism, lipid transport across cellular membranes, and mitochondrial function. Conclusions: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee are characteristic biomarkers of lipid metabolism abnormalities in AP. These findings are crucial for a deeper understanding of lipid metabolism pathways in AP and for the early implementation of preventive clinical measures, such as the control of blood lipid levels. Full article

Background/Objectives: Nopalea cochenillifera (L.) Salm-Dyck cladodes are rich in dietary fiber, polyphenols, and minerals, which are known to exert antioxidant and immunomodulatory effects. However, the mechanisms and active constituents have not been fully elucidated. In this study, we investigated the effects of continuous N. cochenillifera consumption on lipid metabolism, immune function, and the gut microbiota in mice. Methods: The feed was made using freeze-dried and powdered cladodes of N. cochenillifera. Male C57BL/6J mice were assigned to four groups: control diet (C), control diet plus 10% N. cochenillifera (CN), high-fat diet (FC), and high-fat diet plus 10% N. cochenillifera (FN). Results: Cactus supplementation reduced the body and liver weights that were elevated by the high-fat diet. Serum total cholesterol and free fatty acids were increased in the FC group compared with the C group, while cactus intake lowered these levels and enhanced fecal cholesterol excretion. Cactus consumption also elevated fecal total IgA and mucin contents. IL-4 expression in Peyer’s patches was significantly increased in the FN group compared with the FC group. Gut microbiota analysis showed significant differences in β-diversity, along with increased α-diversity and higher abundance of Lachnospiraceae, following cactus intake. Conclusions: These findings suggest that N. cochenillifera intake increases gut microbiota diversity, which enhances intestinal barrier function and thereby contributes to improved lipid metabolism and immune regulation. Full article

The gut microbiome is essential for gut health, immune regulation, and metabolism, but pathogenic bacteria like Enterococcus and Streptococcus can disrupt these processes, increasing infection risk after colorectal surgery. Prior studies show that intravenous antibiotics and surgical bowel preparation (SBP, including mechanical preparation with oral antibiotics) significantly disrupt the gut microbiota, potentially delaying postoperative recovery. However, the effects of surgical indication (e.g., diagnosis) and operation type on gut microbiome composition and function remain unclear. This study examines how SBP, resectional and non-resectional surgery, and underlying diagnoses shape the postoperative gut microbiome and microbial recovery. Methods: Fecal samples were collected from patients undergoing colonoscopy (n = 30), non-resectional (ventral mesh rectopexy, transanal surgery; n = 25), or resectional surgery with primary anastomosis (n = 26) at baseline, intraoperatively, and on postoperative days (POD) 10, 30, and 180. Microbial diversity was assessed through 16S rRNA sequencing, and short-chain fatty acid (SCFA) levels were measured to evaluate functional changes. Results: Alpha diversity (Shannon indices) decreased across all groups, recovering by POD10 in colonoscopy patients and by POD180 in non-resectional and resectional cohorts. Beta diversity (community composition) also returned to baseline by POD10 in colonoscopy patients and POD180 in non-resectional patients, but the resectional cohort did not fully recover (p < 0.001). Both surgical cohorts showed substantial losses of commensal bacteria through POD30, with notable increases in Streptococcus in resectional patients (p < 0.0001) and Enterococcus in both surgical cohorts (p < 0.0001). Functionally, only the resectional cohort experienced significant reductions in SCFA levels (p < 0.015) relative to baseline levels. Diagnosis minimally influenced long-term microbiota recovery, although cancer patients tended to have more stable microbiomes compared to patients with diverticulitis. Conclusions: These findings indicate that perioperative factors, especially surgical resection and SBP, significantly impact gut microbial recovery, with pathogenic bacteria persisting up to 6 months post-surgery. Full article

Background/Objectives: Sphingolipids are a class of lipids that play important structural and functional roles in the cell. Specific ceramide species are distinguishable through the fatty acid that is acylated to the sphingosine backbone, leading to distinct biological activities. Generally, long-chain (LC) ceramides (16:0 and 18:0) drive metabolic dysfunction resulting in the progression of different disease states, while very long-chain (VLC) ceramides (22:0 and 24:0) are thought to be either beneficial against disease progression or benign. In this study, we sought to alter the cellular composition of LC and VLC ceramides in ventricular HCMs to investigate how alterations in these lipids can affect the transcriptome of otherwise healthy HCMs. Methods: Here, we used specific siRNA to knockdown the ceramide synthases responsible for the production of LC and VLC ceramides in ventricular HCMs and investigated the changes in the transcriptome of HCMs with CERS2 or CERS5/6 silenced compared to control conditions. Results: Knocking down CERS2 led to an increase in cell death as well as widespread reductions in cellular VLC sphingolipids. Additionally, we demonstrated that VLC sphingolipid species may play a protective role in maintaining cardiovascular function and that reducing these lipids may contribute to cardiac dysfunction. Similarly, knocking down CERS5 and CERS6 led to reduced LC ceramides and also resulted in profound changes in gene transcription. Interestingly, multiple genes and pathways were affected in the opposite direction when compared to the changes observed with the CERS2 knockdown. Conclusions: Taken together, our results suggest pathways through which VLC ceramides may contribute to cardiac protection, and pathways where LC ceramides may promote HCM stress and the development of cardiac disease. Full article

Salinity is a key environmental factor regulating lipid metabolism in marine oleaginous protists. This study examined the impact of NaCl concentration on growth, glucose utilization, and lipid biosynthesis in Thraustochytrium sp. ATCC 26185. Moderate salinity (20 g/L) enhanced biomass and glucose uptake, while high salinity (45 g/L) induced osmotic stress yet significantly promoted squalene accumulation (17.27 mg/g), a 3.26-fold increase compared with 0 g/L NaCl (5.29 mg/g). Integrated transcriptomic and metabolomic analyses revealed that salinity-dependent activation of glycolysis, the TCA cycle, and the pentose phosphate pathway increased cellular ATP, NADH, and NADPH levels. Under salt stress, the mevalonate (MVA) pathway was transcriptionally upregulated, with key enzymes, including ACAT, HMGR, and IDI, showing marked induction, which supports enhanced carbon flux toward squalene biosynthesis. Despite SQS downregulation, squalene accumulation increased, likely due to elevated precursor availability and reduced flux to downstream sterol pathways. Concurrently, high salinity repressed expression of ACC, FAS-α, and FAS-β, reducing saturated fatty acid levels, while upregulation of PKSB-favored polyunsaturated fatty acid (PUFA) synthesis. These findings suggest that high-salt stress triggers transcriptional reprogramming, redirecting acetyl-CoA from fatty acid synthesis toward squalene and PUFA production. This study offers new insights into the metabolic plasticity of thraustochytrids and highlights salinity modulation as a promising strategy for enhancing high-value lipid yields in marine biotechnology. Full article

Background: Fatty acyl–ACP thioesterase (FAT) genes regulate fatty acid composition and content, yet the FAT family in maize has not been systematically characterized. Methods: Ten ZmFAT genes were identified from the maize genome and analyzed for gene structure, protein properties, phylogeny, collinearity, cis-acting elements, and predicted interactions. Transcriptome and qRT–PCR data were used to assess expression patterns during seed development. Results: The ten ZmFAT genes were grouped into two subfamilies (three ZmFATA and seven ZmFATB genes). Two pairs of collinear genes were detected within maize and one pair between maize and rice. Promoter analysis revealed light- and development-responsive elements. Two genes were functionally annotated in fatty acid biosynthesis, while five proteins exhibited interactions and 14 miRNAs were predicted to regulate ZmFAT genes. Expression analysis showed that ZmFATA1/2 and ZmFATB4/6/7 maintained high expression in both upper and lower seed parts, and qRT–PCR confirmed their gradual upregulation during seed development. Conclusion: This study provides the first comprehensive characterization of the maize ZmFAT family, offering insights into fatty acid metabolism and valuable genetic resources for improving maize oil composition. Full article

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) profoundly disrupt lipid metabolism within local microenvironments of skeletal muscle and its associated connective tissues, including adipose tissue, bone, and fascia. However, the role of local communication between skeletal muscle and its proximal connective tissues in propagating metabolic dysfunction is incompletely understood. This narrative review synthesizes current evidence on these local metabolic interactions, highlighting novel insights and existing gaps. Methods: We conducted a comprehensive literature analysis of primary research published in the last decade, sourced from PubMed, Web of Science, and ScienceDirect. Studies were selected for relevance to skeletal muscle, adipose tissue, fascia, and bone lipid metabolism in the context of obesity and T2DM, with emphasis on molecular, cellular, and paracrine mechanisms of local crosstalk. Findings were organized into thematic sections addressing physiological regulation, pathological remodeling, and inter-organ signaling pathways. Results: Our synthesis reveals that local lipid dysregulation in obesity and T2DM involves altered fatty acid transporter dynamics, mitochondrial overload, fibro-adipogenic remodeling, and compartment-specific adipose tissue dysfunction. Crosstalk via myokines, adipokines, osteokines, bioactive lipids, and exosomal miRNAs integrates metabolic responses across these tissues, amplifying insulin resistance and lipotoxic stress. Emerging evidence highlights the underappreciated roles of fascia and marrow adipocytes in regional lipid handling. Conclusions: Collectively, these insights underscore the pivotal role of inter-tissue crosstalk among skeletal muscle, adipose tissue, bone, and fascia in orchestrating lipid-induced insulin resistance, and highlight the need for integrative strategies that target this multicompartmental network to mitigate metabolic dysfunction in obesity and T2DM. Full article

Environmental salinity is a critical factor influencing the physiological and metabolic processes of teleosts. Despite its importance, the molecular mechanisms underlying these responses, particularly those involving specific signaling pathways and gene expression regulation, remain poorly understood. To elucidate the role of lipid metabolism in osmotic regulation, the present study investigated the effects of varying salinity levels (2, 20, 40, and 60 ppt) on growth performance and metabolic status, including the biosynthesis of LC-FAs and VLC-FAs, respectively, in neural tissues (brain and eyes), of the euryhaline fish Fundulus heteroclitus over a 62-day period. The findings revealed multiple physiological adaptations to salinity variation, encompassing both molecular and metabolic responses. Salinity had a significant impact on growth performance, with fish exposed to the highest salinity level (60 ppt) exhibiting reduced growth. At this salinity, plasma levels of lipid-related metabolites, i.e., triglycerides and cholesterol, were decreased, whereas both osmolality and cortisol levels increased. Hepatic glucose and lactate levels increased with rising salinity, while glucose and triglyceride concentrations in muscle tissue declined. Additionally, intestinal lipase activity was significantly higher at 60 ppt. Although no significant differences were observed in the total UFAs content of both tissues, in the brain, significant differences were detected in the levels of 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-3, 20:4n-6, and 20:5n-3, whereas in the eye, differences were observed only for 16:1n-7 and 20:5n-3. Gene expression analysis revealed that salinity exerts a regulatory effect on the expression of fads2b and elovl4a in the eye, with up-regulation observed at 60 ppt. In contrast, no significant changes in the expression of fads or elovl genes were detected in the brain. These findings highlight the contribution of non-osmoregulatory organs, such as the brain and eyes, in the osmotic adaptation of teleosts. Collectively, the results suggest that lipid metabolism plays a key regulatory role in the adaptation of F. heteroclitus to salinity fluctuations. Full article

Human gut Bacteroides species play crucial roles in the metabolism of dietary polysaccharides. Polyguluronate (PG), a major component of alginate, has been widely used in the food and medical industries. However, how PG is utilized by human gut Bacteroides species has not been fully elucidated. Here, using a combination of culturomics, genomics, and state-of-the-art analytical techniques, we elucidated in detail the utilization profiles of PG by 17 different human gut Bacteroides species. Our results indicated that each Bacteroides species exhibited a unique capability for PG utilization. Among all species tested, Bacteroides xylanisolvens consumed the highest amount of PG and produced the greatest quantity of short-chain fatty acids, suggesting that it may be a keystone bacterium in PG utilization. Mass spectrometry showed that PG was degraded by B. xylanisolvens into a series of oligosaccharides. Genomic analyses confirmed that B. xylanisolvens possesses a large and divergent repertoire of carbohydrate-active enzymes. Moreover, genomic annotation identified two enzymes, PL17_2 and PL6_1, in B. xylanisolvens that are potentially responsible for PG degradation. Altogether, our study provides novel insights into PG utilization by human gut Bacteroides species, which has important implications for the development of carbohydrate-based drugs from marine resources. Full article

Weaning stress in piglets severely restricts swine production efficiency due to growth retardation, immune suppression, and intestinal dysfunction. This study investigated the effects of dietary pyrroloquinoline quinone (PQQ) on 36 weaned piglets (22 ± 1 days old) allocated to six groups (0, 1, 2, 4, 8 and 16 mg/kg PQQ) for 28 days. Results showed that 4–8 mg/kg PQQ improved average daily gain and feed conversion ratio (p < 0.05), enhanced serum immunoglobulin (IgA, IgG) and antioxidant enzyme (T-AOC, SOD, GSH-Px) levels, and reduced inflammatory cytokines (TNF-α, IL-1β, IL-6) (p < 0.05). PQQ modulated gut microbiota, increasing Lactobacillus and Bifidobacterium, and elevated short-chain fatty acid production (p < 0.05). Metabolomic analysis revealed upregulated tricarboxylic acid (TCA) cycle intermediates (citric acid, isocitric acid and malic acid), indicating improved mitochondrial function (p < 0.05). Overall, 4 mg/kg PQQ optimally alleviates weaning stress by enhancing immunity, gut health, and energy metabolism, offering a promising strategy for piglet nutrition. Full article

Microalgae are unicellular photosynthetic organisms with considerable genetic diversity and remarkable metabolic capacity, positioning them as sustainable cellular biorefineries. They can be cultivated in open or closed systems, influenced by physical and chemical variables such as light, temperature, and nutrient availability. These conditions modulate the synthesis of valuable biomolecules, including proteins, lipids, polysaccharides, and secondary metabolites. Microalgae are especially notable for their high protein content (up to 70% w/w in Spirulina sp.), polyunsaturated fatty acids (e.g., DHA and EPA), and β-glucans with bioactive properties. Choosing the correct extraction method (mechanical, enzymatic or combined) is very important to obtain and preserve the functionality of these compounds. Despite their biotechnological potential in functional foods, pharmaceuticals, and biofuels, industrial development faces challenges such as extraction efficiency, scalability, and regulatory approval. This review compiles current knowledge on the nutritional and bioactive potential of microalgae, highlights advances in extraction technologies and discusses their potential applications in health-oriented industrial innovation. Full article

Sour camel milk, as a nutritious fermented dairy product, faces challenges in terms of quality stability. Sparassis crispa, due to its antioxidant and antibacterial properties, shows potential in improving food quality. This study aimed to investigate the effects of different active components of Sparassis crispa on the quality of sour camel milk. The results indicated that Component I was the most effective Sparassis crispa component in enhancing the quality of sour camel milk. The components of Component I were identified as LysoPC(0_0_18_2(9Z,12Z)), LysoPC(18_1(11Z)_0_0), and N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl) anthranilic acid, among others. It increased the total viable count of lactic acid bacteria (LAB) and water-holding capacity (WHC) while improving the texture of sour camel milk. Metabolomics analysis revealed that the first component of sour camel milk (FCS) and Sparassis crispa sour camel milk (SS) have a high degree of similarity in the composition of flavor substances. The characteristic flavor metabolites included 2-amylfuran, isoamyl alcohol, 2-methylbutyraldehyde, and 2-ethyl-1-hexanol. Additionally, the supplementation of Component I increased the levels of metabolites such as amino acids, free fatty acids, organic acids, and carbohydrates, thereby contributing to the enhanced taste and nutritional quality of sour camel milk. This intervention also strengthened carbohydrate and amino acid metabolism in LAB. These findings provide a theoretical basis for utilizing Component I to improve the quality of sour camel milk. Full article

The peroxisome proliferator-activated receptor family of lipid-activated nuclear receptors (PPARs) plays a critical role in the regulation of cellular lipid metabolism. In cardiac muscle, PPARα is highly expressed and regulates genes involved in fatty acid oxidation, but its activity is downregulated in hypertrophic hearts; however, the consequences of chronic PPARα deficiency on the cardiac contractile apparatus remain unclear. This study aimed to investigate the PPARα role in hypertrophic phenotype and to evaluate the potential effects of the antioxidant Ebselen (Ebs) treatment on changes associated with PPARα depletion. We thus generated an in vitro model of cardiac hypertrophy by stable silencing of the PPARA gene in H9c2 rat cardiomyoblasts. We observed that PPARα silencing induces a hypertrophic phenotype, characterized by increased NPPB and decreased FBXO32 expression, mitochondrial dysregulation, impaired lipid metabolism, oxidative stress, and ferroptosis-related alterations. Epigenetically, H3K27ac levels increased while H3K27me3 decreased. Moreover, miR-34a, miR-132, and miR-331 were downregulated, implicating a miRNA-mediated mechanism in PPARα-linked cardiac hypertrophy. Treatment with Ebs, a redox-active compound with inhibitory effects on ferroptosis and epigenetics, reversed hypertrophic phenotype and restored miRNA levels. In conclusion, we found that PPARα depletion promotes oxidative stress and hypertrophic phenotype and that Ebs may act as a potential therapeutic agent. Full article