Search Results (15,755)

Canarii Fructus (Canarium album) is a rich source of polyphenols with significant potential for functional food applications. This review summarizes recent advances in the composition, extraction technologies, biological activities, and utilization prospects of Canarii Fructus polyphenols (CFPs). More than 30 polyphenolic compounds have been identified, with gallic acid and ellagic acid as the major constituents, accounting for approximately 38.8% and 14.3% of the total phenolics, respectively. The fruit contains about 300 mg/100 g fresh weight of phenolic compounds. Emerging extraction technologies, including ultrasound-assisted extraction, microwave-assisted extraction, and ultrasound–microwave-assisted extraction (UMAE), have improved extraction efficiency, with UMAE achieving yields of up to 6.33% within 4.4 min. Unlike previous studies focusing primarily on phytochemical characterization or pharmacological activities, this review provides a comprehensive food-oriented perspective by integrating chemical diversity, extraction strategies, molecular mechanisms, bioavailability challenges, and functional food applications of CFPs. CFPs exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antitumor, anti-aging, hepatoprotective, and metabolic regulatory activities through pathways including Nrf2/ARE, NF-κB, PI3K/Akt, and AMPK. Representative bioactivities include α-glucosidase inhibition (IC₅₀ = 9.914 × 10⁻³ μg/mL) and regulation of lipid metabolism via AMPK activation. Particular attention is given to emerging approaches, including green extraction technologies, nanodelivery systems, and AI-assisted target discovery. Current limitations related to low bioavailability, unclear structure–activity relationships, and insufficient in vivo evidence are also discussed. Overall, CFPs represent a promising natural resource for the development of functional foods and nutraceuticals. Full article

Background/Objectives: The glucocorticoid receptor (GR) is essential for regulating liver energy balance, metabolism, and inflammation. Stress and other factors can impair its function, resulting in glucocorticoid-resistant metabolic liver disease. GR mainly exists in two forms: the glucocorticoid-binding isoform, GRα, and the non-binding isoform, GRβ. The GRβ isoform typically exhibits minimal signaling activity beyond its role as a dominant-negative regulator of GRα, thereby decreasing glucocorticoid responsiveness and potentially causing resistance. Methods: To explore GRβ signaling independent of GRα, we developed mice with adenovirus-induced overexpression of GRβ (GRβ-Ad) and control mice with a vector (Vec-Ad). After five days on a standard diet, these mice received either vehicle or dexamethasone treatment. Liver tissues were collected, and we performed RNA sequencing and advanced PamGene kinome analysis to detect pathway changes in GRβ-Ad mice compared with controls. Results: Significant increases were observed in the expression of genes that inhibit fatty acid oxidation, inflammation, and liver cancer development. There was also a marked difference in serine/threonine kinase activity between GRβ-Ad and control mice. Conclusions: The findings suggest that elevated GRβ levels affect kinase pathways that modulate glucocorticoid signaling, disrupt liver lipid metabolism, and are associated with cancer pathways. Further research is needed to determine whether GRβ functions similarly in humans and to assess its potential contribution to hepatocellular carcinoma (HCC). Full article

Sericin-derived oligopeptides (SDOs) from the Bombyx mori yellow silk cocoons show strong bioactive properties. However, clinical safety data on SDOs produced by specific enzymatic hydrolysis with a particular serine-rich (20.5%) and aspartic acid-rich (16.9%) composition is required to obtain regulatory approval as a novel food ingredient. This Phase 0 randomized, double-blind, placebo-controlled trial evaluated the short-term safety, tolerability, and gut microbiota effects of SDOs supplementation in healthy adults. Forty-two healthy volunteers were randomized (1:1:1) to receive daily doses of placebo, 0.9 g SDOs or 1.8 g SDOs for eight weeks. Primary safety endpoints included vital signs, hematology, and comprehensive clinical chemistry (renal and hepatic functions). Secondary outcomes included lipid profiles, oxidative stress markers (hs-CRP, TAC, SOD, MDA) and gut microbiota composition analyzed by 16S rRNA metagenome sequencing. Forty-one participants (97.6%) completed the study with high compliance (>98%). No serious adverse events were reported. All primary clinical parameters remained within clinically normal ranges, and no significant differences between groups were observed throughout the study (p > 0.05). No adverse effects on fasting blood glucose, lipid profiles or systemic oxidative stress were observed after SDOs supplementation. Importantly, 16S rRNA sequencing analysis showed that SDOs maintained gut microbial homeostasis throughout the 8-week intervention period, with Bacteroidetes and Firmicutes as the predominant phyla in the core community structure. Oral intake of enzymatically generated SDOs up to 1.8 g/day in healthy adults was well-tolerated with only occasional mild and transient gastrointestinal symptoms that did not appear to be dose-dependent. These first preliminary findings suggest a favorable safety profile for this unique peptide preparation, supporting its potential evaluation as a novel food ingredient and providing a reasonable basis for future, larger-scale trials to evaluate its efficacy in metabolic health. Full article

Evidence from clinical trials indicates that dietary protein plays an important and often underappreciated role in lipoprotein lipid metabolism. For this narrative review, literature searches were conducted in the PubMed and Cochrane Central Register of Controlled Trials databases for articles describing randomized controlled trials (RCTs) and systematic reviews and meta-analyses of RCTs, as well as dietary guidelines and dyslipidemia management recommendations, using search terms for protein quantity, source (e.g., animal- and plant-based), and type (e.g., dairy, meat, soy, and nuts) and effects on lipids and lipoproteins in humans. Findings indicated that dietary intakes of both animal-based and plant-based proteins, when replacing refined carbohydrates or saturated fatty acids, lower circulating concentrations of atherogenic lipoproteins. Protein from plant sources appears to produce a somewhat larger effect on lipoprotein lipid concentrations than protein from animal sources. Individual amino acids (e.g., branched-chain amino acids), protein food fractions (e.g., whey), and food-derived peptides may independently impact lipoprotein lipid metabolism. Beyond the effect of replacing one macronutrient for another, the biochemical pathways responsible for the effects of dietary protein on lipoprotein lipid metabolism in humans have not been fully defined. The importance of dietary protein in a healthy diet is emphasized in recent dietary recommendations for the general population and for individuals with dyslipidemias. Additional research is warranted to determine the amount of dietary protein and the best balance of food source(s) to optimize its benefits on lipoprotein lipid concentrations, as well as the mechanisms for these effects. Full article

This study investigated the effects of long-term dietary choline supplementation on the productive performance, liver characteristics, and egg quality of brown laying hens during an extended laying cycle from 66 to 100 weeks of age. A total of 240 Hy-Line Brown laying hens were randomly allocated to four dietary treatments containing 0%, 0.07%, 0.28%, or 0.84% supplemental Choline-50%, with six replicates per treatment. Production performance was monitored throughout the experiment, and samples for physiological analyses were collected at 100 weeks of age. Egg production during 66–75 weeks increased linearly with increasing dietary choline levels (p < 0.05), whereas no significant differences were observed between weeks 76 and 100. Choline supplementation significantly decreased liver fat content and malondialdehyde concentration (p < 0.01), indicating improved hepatic lipid metabolism and reduced oxidative stress. Small white and yellow follicle counts increased (p < 0.05), suggesting enhanced early follicular development. Serum inorganic phosphorus levels decreased linearly (p < 0.01), whereas the other blood biochemical traits were unaffected. Dietary treatments did not influence bone quality traits. Yolk weight decreased in the choline-supplemented hens (p < 0.05), whereas albumen quality and shell traits remained unchanged. In conclusion, dietary choline supplementation may improve liver health and maintain productivity during production cycles extending up to 100 weeks of age. Full article

Background/Objectives: Styphnolobium japonicum cv. Jinhuai (SJvJ) represents a medicinal and edible plant whose metabolite composition is strongly shaped by its growing location. Current quality control methods mainly rely on rutin quantification, lacking comprehensive metabolic markers for origin discrimination. Therefore, this study aimed to profile interregional metabolic differences between Guangxi and Sichuan SJvJ flower buds, identify characteristic differential markers, and clarify relevant metabolic pathways, thereby guiding quality control, germplasm evaluation, and functional food development. Methods: Ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was employed to identify metabolites. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Cancer HSP were applied to screen the key active ingredients of traditional Chinese medicine (TCM-KAIs) and disease-related pharmaceutical ingredients (PDRIs). Specifically, we targeted six highly prevalent human diseases and another five disorders based on therapeutic indications documented in the Chinese Pharmacopoeia. Multivariate analyses, such as principal component analysis, hierarchical clustering analysis, and other statistical methods, were applied to investigate differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was utilized for pathway enrichment analysis of marker metabolites. Results: In total, 1550 metabolites were identified across 12 categories, predominantly flavonoids. Additionally, 152 TCM-KAIs and 204 PDRIs against 11 diseases were screened. Multivariate analyses indicated that geographical origin was closely associated with observed metabolic variation among the tested samples: Guangxi samples accumulated higher lipids and nucleotides, whereas Sichuan samples showed higher levels of flavonoids and phenolic acids. Vanilloloside, protocatechuic acid-4-O-glucoside, and gallic acid-4-O-glucoside were identified as key inter-group biomarkers. KEGG enrichment analysis revealed enhanced metabolism of nucleotide/pyrimidine in Guangxi, whereas zeatin biosynthesis was upregulated in Sichuan, consistent with discrepancies in regional climatic patterns. Conclusions: This study established a more comprehensive metabolomic dataset for FBSJvJ. It also clarified the correlations between origin and quality and unraveled the underlying mechanisms. These findings facilitate origin authentication, standardized quality control, and rational exploitation of FBSJvJ as raw materials of functional foods. Full article

Background/Objectives: The gut–brain axis and systemic metabolic dysregulation are increasingly implicated in Alzheimer’s disease (AD) pathogenesis. This study aimed to characterize gut microbiota and plasma metabolomic profiles associated with amyloid pathology and cognitive impairment in patients with mild cognitive impairment (MCI). Methods: A cross-sectional multi-omics baseline analysis was performed in 47 MCI patients enrolled in a randomized, double-blind, crossover dietary intervention trial (NCT05029765). Gut microbiota composition was assessed by 16S rRNA sequencing (n = 47), and plasma metabolomics by untargeted LC-MS/MS (n = 45 after exclusion of two PCA-defined metabolomic outliers). Patients were stratified according to plasma amyloid-beta 42/40 ratio (BA42/40) and ADAScog11 score, representing complementary biomarkers of amyloid burden and cognitive impairment, respectively. Results: Higher amyloid burden and worse cognitive performance were associated with significant gut microbiota alterations, including increased alpha diversity and distinct beta diversity profiles. Differential abundance analyses consistently showed enrichment of Bacteroides-associated taxa and Akkermansia, alongside depletion of short-chain fatty acid-producing genera such as Faecalibacterium, Blautia, and Phascolarctobacterium. Plasma metabolomics identified a coherent signature associated with elevated BA42/40, characterized by accumulation of secondary bile acid sulfates and depletion of sphingolipids, neuroactive steroids, and anti-inflammatory lipid mediators, including pregnenolone sulfate, resolvin E1, and anandamide. A valid OPLS-DA discriminant model was obtained for BA42/40, whereas no predictive model was achieved for ADAScog11. Critically, this dissociation, characterized by significant microbiota differences but no metabolomic separation for ADAScog11, is itself an informative finding, suggesting that gut microbiota dysbiosis and plasma metabolomic alterations are not equally coupled to both dimensions of MCI pathophysiology. Conclusions: MCI patients with greater amyloid pathology and cognitive impairment exhibited gut microbiota dysbiosis. However, metabolic associations were observed only for BA42/40, but not for ADAScog11. These findings provide a mechanistic framework for evaluating the impact of Mediterranean diet and probiotic interventions in the longitudinal phase of the trial. Full article

Apolipoprotein A-IV (ApoA-IV) is a glycoprotein secreted by the small intestine to regulate lipid metabolism and satiety. Its role in insulin-independent glucose homeostasis remains largely unknown. In this study, we demonstrate that intestinal ApoA-IV overexpression significantly attenuates diet-induced obesity and hyperglycemia following severe β-cell loss. Over a 20-week high-fat diet challenge, ApoA-IV transgenic (ApoA-IV-Tg) mice maintained significantly lower adiposity than wild-type controls, driven by elevated energy expenditure and fatty acid oxidation rather than reduced caloric intake. Beyond weight maintenance, ApoA-IV maintained excellent systemic glycemic control and enhanced peripheral insulin sensitivity. Most notably, ApoA-IV significantly attenuated hyperglycemia following streptozotocin (STZ)-induced β-cell ablation, maintaining glucose stability despite severe insulin deficiency. Mechanistically, this protection results from a blunted glucagon response and the subsequent suppression of the hepatic pCREB-G6Pase gluconeogenic signaling pathway. In vitro evidence confirms that ApoA-IV directly inhibits pancreatic α-cell glucagon secretion through an LDL receptor-related protein 1 (LRP1)-dependent pathway, reinforced by the precise co-localization of LRP1 and glucagon in pancreatic islets. Furthermore, ApoA-IV-Tg mice were protected from the STZ-induced corticosterone surge and systemic lipolysis. Collectively, these findings establish the ApoA-IV–LRP1 signaling axis as a potent metabolic switch, providing a promising insulin-independent strategy for managing obesity and diabetes. Full article

Increasing evidence highlights a tight interplay between lipid metabolism and mitochondrial homeostasis in neurons, with disruptions in either pathway amplifying cellular vulnerability. PTEN-induced kinase 1 (PINK1), a familial Parkinson’s disease (PD)-related gene and a key regulator of mitochondrial quality control and homeostasis, emerges at the intersections of lipid metabolic pathways, influencing membrane composition, fatty acid utilization, and neuronal energy balance. Within this review, we discuss the role of mitochondria as hubs for lipid metabolism, the mechanisms and functional consequences of neuronal lipid handling, and the complex bidirectional relationship between lipid dysregulation and PD pathology. Special focus is given to lipid–mitochondria crosstalk and how PINK1 orchestrates this interface to maintain neuronal homeostasis. Finally, we consider therapeutic perspectives that target lipid and mitochondrial pathways, highlighting strategies to restore cellular function and PD pathology. Full article

Gammaherpesviruses (GHVs) represent a global clinical burden as the causative agents of Kaposi’s sarcoma and mononucleosis, among other diseases. Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV) are the most studied human GHVs, and murine gammaherpesvirus 68 (MHV-68) is a recognized experimental model. GHVs are defined by their modulation of the host cell to establish lifelong latent infections and increase host dysregulation during periodic reactivation. Due to their ubiquitous changes in host cells, systems-level techniques are well-suited to study GHV infections at all stages of the central dogma: genomics, transcriptomics, and proteomics. Furthermore, metabolomics can reveal the final metabolic changes across numerous host cellular pathways. This review assesses the current knowledge on GHV infections gained through omics techniques. We also identify gaps and propose future directions, including the development of new therapeutic strategies. Early omics techniques have characterized large swaths of infection for EBV, KSHV, and MHV-68, revealing conserved genes, homologous transcripts, and proteins. Modern omics techniques have enabled higher-resolution studies, yielding insights into heterogeneity in viral-host gene, transcript, and protein modulation strategies across geographical populations, viral subtypes, inter- and intra-patient infections, and latent and lytic states. The metabolome during GHV infections remains the least understood, but current studies have identified essential modulations of nucleotide, amino acid, and lipid synthesis by EBV, KSHV, and MHV-68. Importantly, the application of integrative omics methods to GHV infections remains a promising direction of study as the increased resolution of modern techniques meets the need for greater understanding of differences in each GHV infection. Full article

Spirulina-derived protein hydrolysates (SPPHs) have attracted considerable attention as bioactive agents due to their potential metabolic and physiological benefits. This study evaluated the therapeutic efficacy of different enzyme-specific SPPHs—Pepsin (SPPH-P), Trypsin (SPPH-T), Chymotrypsin (SPPH-C), and a combined hydrolysate (SPPH-PTC)—in high-fat diet (HFD)-induced male Wister rats, compared with Spirulina platensis protein extract (SPPE, formulated using freeze–thaw cycles and ultrasonication followed by centrifugation) and atorvastatin as a Positive Control. The animals were randomly allocated into seven groups (n = 6 per group) and received their respective treatments orally for 4 weeks. Across treatment groups, significant improvements in obesity-related anthropometric indices were observed, including reductions in BMI, Lee Index, and abdominal circumference to thoracic circumference ratio (AC:TC), with the strongest effects noted in the atorvastatin and SPPH-PTC groups. Protein metabolism markers showed enhanced hepatic and serum protein status, reflected by increased albumin and total protein concentrations. Lipid profile analysis revealed marked decreases in total cholesterol, triglycerides, and LDL in both serum and liver homogenates, while HDL exhibited non-significant but favorable elevations. Liver function markers (bilirubin, ALT, AST) and renal parameters (uric acid, BUN) demonstrated notable improvements, particularly in enzyme-derived hydrolysate groups and Positive Control. Antioxidant assessments indicated substantial reductions in MDA levels and significant increases in SOD, CAT, and GSH activities in serum and liver tissues, confirming enhanced oxidative stress resistance. Among all treatments, SPPH-PTC consistently produced the most robust therapeutic outcomes. Overall, Spirulina protein hydrolysates, especially the combined PTC formulation, exert comprehensive beneficial effects on metabolic regulation, hepatic and renal function, and oxidative balance. These findings support their potential application as functional bioactive agents for managing obesity-associated metabolic disturbances. Full article

Fat deposition determines beef marbling grade and meat quality, but the underlying molecular mechanisms remain unclear. This study aimed to investigate the role of bovine PPARD in lipid deposition, especially its effect on the expression of fatty acid transport genes (CD36, FATP1, and FABP1) and the lipid droplet-associated gene (PLIN2) in liver tissues from cattle with different marbling grades. The mRNA abundance and protein levels in liver tissues from thirty-one Wagyu × Angus crossbred beef cattle (25–26 months old) with different marbling grades (according to GB/T 29392-2022, based on the marbling richness of the longissimus dorsi muscle at the 12th–13th rib interface) were analyzed by RT-qPCR and Western blot, respectively. Additionally, PPARD was knocked down and overexpressed in bovine mammary epithelial cells to validate its effects on lipid-metabolism-related genes. The results showed that the mRNA levels of CD36, FATP1, PPARD, RXRA, RXRB, and PLIN2 were significantly higher (p < 0.01) in livers tissues from the A3 and A4 groups (high marbling) than in those from the A1 and A2 groups (low to moderate marbling). Western blot analysis revealed significantly higher PPARD protein expression in the A3 and A4 groups (high marbling) than that in the A1 and A2 groups (low to moderate marbling) (p < 0.05). It should be noted that the sample size of Group A4 is only 2, and the results of this group should be considered as a preliminary trend that needs to be validated with larger sample sizes. Cellular experiments confirmed that PPARD knockdown significantly decreased mRNA expressions of FABP1, CD36, and PLIN2 (p < 0.01), while PPARD overexpression significantly increased their mRNA levels (p < 0.05). These results indicate a positive correlation between PPARD expression and the transcriptional levels of genes involved in fatty acid transport and lipid droplet storage, suggesting that PPARD may be associated with hepatic lipid metabolism and potentially contribute to marbling development. These findings suggest that the PPARD signaling pathway contributes to hepatic lipid deposition and may play a role in marbling formation in beef cattle. Full article

Background/Objectives: Dolphins inhabiting coastlines can be influenced by anthropogenic factors. As biochemical changes accumulate in blubber over weeks to months, blubber metabolites may be informative biomarkers of molecular adaptations to environmental changes. Methods: We investigated the blubber metabolomic signatures of live free-ranging bottlenose dolphins for the first time. This exploratory study analyzed blubber samples from 35 common bottlenose dolphins (Tursiops truncatus) in South Texas waters using untargeted ultra-high-performance liquid chromatography-Orbitrap metabolomics. Results: Blubber samples exhibited distinct temporal and spatial metabolic patterns. Pathway enrichment analyses comparing detected metabolites (n = 2777) revealed that dolphins sampled in the spring had enhanced lipid quality and immune regulation, while dolphins sampled in the summer showed stress-associated metabolic responses. Dolphins inhabiting areas previously reported to experience heavy vessel traffic and contaminant burdens exhibited enriched immune- and inflammation-associated pathways. Dolphins that visually appeared to have poorer body condition exhibited metabolite profiles suggestive of increased protein catabolism. Dolphins in extreme salinity conditions had more abundant membrane maintenance and endocrine pathways. Conclusions: Dolphins from each system exhibited distinct metabolic signatures that may be associated with differing physiological responses, highlighting the potential utility of blubber biomarkers for assessing physiological adaptations in free-ranging marine mammals. Improved understanding of habitat-specific physiological responses offers critical insights into how cumulative impacts may affect the health and adaptive capacity of vulnerable species in dynamic coastal ecosystems. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly associated with cardiovascular disease. Identifying early manifestations of vascular aging before the onset of overt disease is essential for improving cardiovascular risk stratification and prevention. Emerging evidence suggests that PFAS exposure contributes to early vascular and atherosclerotic alterations detectable by imaging techniques, including increased carotid intima–media thickness (CIMT), arterial stiffness, and endothelial dysfunction. In contrast, evidence for associations with coronary artery calcium progression and coronary stenosis remains scarce. Mechanistically, PFAS exposure promotes endothelial dysfunction, oxidative stress, chronic inflammation, lipid dysregulation, and genetic and epigenetic modifications, all of which contribute to premature vascular aging and metabolic disturbances. The integration of imaging and molecular biomarkers may provide complementary insights into the structural, functional, and biological processes underlying PFAS-related vascular damage; however, to date, this field remains largely unexplored. This narrative review summarizes current evidence on imaging and molecular biomarkers of PFAS-induced vascular aging and discusses their potential role in cardiovascular risk assessment. It also highlights key knowledge gaps and the need for robust epidemiological and multi-omics studies to validate these biomarkers, clarify causal mechanisms, and support their application in cardiovascular and environmental health surveillance. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the leading cause of hepatocellular carcinoma (HCC) globally. HCC surveillance is currently restricted to patients with cirrhosis, leaving those without cirrhosis, who present with more advanced disease and poorer outcomes without adequate risk stratification tools. This study compared lipid profiles across MAFLD and MAFLD-related HCC (MAFLD-HCC) patients, with and without cirrhosis, to characterise metabolic dysregulation underlying non-cirrhotic MAFLD-HCC (ncMAFLD-HCC). Plasma and liver lipidomic profiles were obtained from 221 patients (140 MAFLD, 66 cirrhotic MAFLD-HCC (cMAFLD-HCC), and 15 ncMAFLD-HCC) using untargeted liquid chromatography mass spectrometry. Univariate, multivariable and enrichment analyses were performed for statistically determining the lipid profile difference between the groups. Seventy percent of lipid classes were more abundant in MAFLD than in ncMAFLD-HCC and cMAFLD-HCC. Multivariate analysis revealed distinct lipid profiles across the three groups in both plasma and liver. Over 100 lipid species including diglyceride (DAG), sphingomyelin (SM), triglyceride (TG), dihydroceramide (DHCer), and linoleic acid derivatives were differentially expressed in ncMAFLD-HCC versus MAFLD, with enrichment in pathways such as glycerolipid metabolism, G-protein signalling, MAPK signalling, EGFR-TKI resistance pathway, implicated in HCC development. ncMAFLD-HCC exhibits a distinct lipid signature, offering preliminary mechanistic insight and a foundation for non-invasive biomarker development. Full article