Search Results (111)

Maternal obesity programs the fetus for increased risk of chronic disease development in early life and adulthood. We hypothesized that maternal nutrient excess leads to fetal inflammation and impairs offspring skeletal muscle mitochondrial biogenesis in non-human primates. At least 12 months before pregnancy, female baboons were fed a normal chow (CTR, 12% energy fat) or a maternal nutrient excess (MNE, 45% energy fat, and ad libitum fructose sodas) diet, with the latter to induce obesity. After 165 days of gestation (0.9 G), offspring baboons were delivered by cesarean section, and the soleus muscle was collected (CTR n = 16, MNE n = 5). At conception, MNE mothers presented increased body fat and weighed more than controls. The soleus muscle of MNE fetuses exhibited increased levels of stress signaling associated with inflammation (TLR4, TNFα, NF-kB p65, and p38), concomitant with reduced expression of key regulators of mitochondrial biogenesis, including PGC1α, both at the protein and transcript levels, as well as downregulation of PPARGC1B, PPARA, PPARB, CREB1, NOS3, SIRT1, SIRT3. Decreased transcript levels of NRF1 were observed alongside diminished mitochondrial DNA copy number, mitochondrial fusion elements (MFN1, MFN2), cytochrome C protein levels, and cytochrome C oxidase subunits I and II transcripts (cox1 and cox2). MNE coupled to MO-induced stress signaling in fetal baboon soleus muscle is associated with impaired mitochondrial biogenesis and lower mitochondrial content, resembling the changes observed in metabolic dysfunctions, such as diabetes. The observed fetal alterations may have important implications for postnatal development and metabolism, potentially increasing the risk of early-onset metabolic disorders and other non-communicable diseases. Full article

Recent advances in cannabinoid-based therapies identified the natural CB2 receptor agonist β-caryophyllene (BCP) as a promising anti-inflammatory and neuroprotective agent. To further explore its therapeutic potential on the management of neurodegenerative disorders, in the present study we investigated the ability of BCP to prevent neuroinflammation and promote neuroprotection by using both in vitro and ex vivo models of β-amyloid induced neurotoxicity. Our data showed that BCP significantly protected human microglial HMC3 cells from Aβ_25-35-induced cytotoxicity, reducing the release of pro-inflammatory cytokines (TNF-α, IL-6) while enhancing IL-10 secretion. These effects were associated with a reduced activation of the NF-κB pathway, which emerged as a central mediator of BCP action. Notably, the use of CB2R- or PPARγ-selective antagonists revealed that the observed NF-κB inhibition by BCP may involve the coordinated activation of both canonical (e.g., CB2R) and non-canonical (e.g., PPARγ) receptors. Moreover, BCP restored the expression of SIRT1, PGC-1α, and BDNF, indicating the involvement of neurotrophic pathways. Clear neuroprotective properties for BCP have been highlighted in Aβ_1-42-treated brain slice preparations, where BCP demonstrated the rescue of both the amyloid-dependent depression of BDNF expression and long-term synaptic potentiation (LTP) impairment. Overall, our results suggest that BCP constitutes an attractive natural molecule for the treatment of Aβ-induced neuroinflammation and synaptic dysfunction, warranting further exploration for its clinical application. Full article

The gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their combined effects using an in vitro model of the gut-liver-adipose axis. Transwell^® system was used to recreate the interaction between intestinal (CaCo-2), hepatic (HepG2), and adipose (3T3-L1) cells. Cells were treated with Bifidobacterium bifidum GM-25, Bifidobacterium infantis GM-21, Lacticaseibacillus rhamnosus GM-28, and polycosanols. The effects were assessed by analyzing intestinal barrier integrity (TEER, tight junction proteins), hepatic and adipose lipid accumulation (Oil Red O staining), oxidative stress (ROS production, lipid peroxidation), inflammation (TNF-α) and lipid metabolism (CD36, PPARγ, AMPK and SREBP-1 levels). Probiotics and polycosanols improved intestinal integrity, increased butyrate production, and reduced ROS levels. Hepatic lipid accumulation was significantly decreased, with enhanced PPARγ and AMPK activation. In adipocytes, probiotic-polycosanols treatment suppressed SREBP-1 expression, enhanced lipid oxidation, and promoted UCP1 and PGC-1α expression, suggesting activation of thermogenic pathways. These findings underline a possible biological relevance of probiotics and polycosanols in modulating metabolic pathways, improving gut barrier integrity, and reducing inflammation, supporting their role as functional ingredients for metabolic health. Full article

Background: Diet-derived advanced glycation end products (dAGEs) are closely associated with obesity and metabolic disorders. This study investigates the therapeutic potential of myriocin (Myr), a sphingolipid synthesis inhibitor, in counteracting dAGE-induced obesity and its underlying mechanisms. Methods: Male C57BL/6J wild-type mice were randomly assigned to receive either a low-AGE diet or a high-AGE diet with or without the administration of myriocin for a duration of 24 weeks. At the end of the experimental period, blood samples, whole livers, and adipose tissues were harvested for subsequent biochemical, histological, and molecular analyses. Results: Using a 24-week high-AGE diet mouse model, we demonstrate that Myr significantly reduces body weight gain (by 76%) and adipose tissue accumulation, while alleviating hepatic steatosis. Myr improves glucose homeostasis by lowering fasting blood glucose (a 44.5% reduction), enhancing oral glucose tolerance, and restoring hepatic glycolysis/gluconeogenesis balance via upregulating glucokinase and suppressing G6pc. Notably, Myr reduces serum LDL-C, TG, and TC levels by 52.3%, 51.8%, and 48.8%, respectively, and ameliorates liver dysfunction as evidenced by normalized ALT/AST activities. Metabolomics reveal Myr reshapes amino acid, carbohydrate, and lipid metabolism pathways. Mechanistically, Myr suppresses lipogenesis by downregulating Srebp1, Fasn, and Acc, while activating AMPK-PGC1α signaling to enhance mitochondrial biogenesis (a 2.1-fold increase in mtDNA) and thermogenesis via Ucp1 upregulation in brown and white adipose tissues. Conclusions: Our findings unveil Myr as a novel dual regulator of lipid and glucose metabolism through AMPK-PGC1α-mediated mitochondrial activation, providing the first evidence of sphingolipid inhibition as a therapeutic strategy against dAGE-induced metabolic syndrome. This study establishes a multifaceted mechanism involving hepatic lipid regulation, adipose browning, and systemic metabolic reprogramming, advancing potential clinical applications for obesity-related disorders. Full article

Traditional Chinese medicine has long acknowledged the therapeutic potential of Tetradium ruticarpum (A.Juss.) T.G.Hartley together with Coptis chinensis Franch in managing metabolic disorders. However, their combined anti-obesity effects and the underlying mechanisms remain poorly characterized. This study investigates the synergistic anti-obesity effects and mechanisms of a combined berberine and evodiamine treatment (BBE) in high-fat diet (HFD)-induced C57BL/6J mice and 3T3-L1 cells. In vitro, cell viability was evaluated using the Cell Counting Kit-8 (CCK-8), while lipid accumulation was assessed through Oil Red O staining and triglyceride content determination. Molecular docking simulations performed with AutoDockTools 1.5.6 software Vina predicted interactions between BBE and key proteins. The analysis of genes and proteins involved in browning and thermogenesis was conducted using quantitative reverse transcription polymerase chain reaction and Western blotting. In vivo, HFD-induced mice were assessed for serum lipids profiles, glucose, insulin, adipocytokines, fat tissue morphology (Hematoxylin and eosin staining), mitochondrial activity (flow cytometry), and protein expression (immunofluorescence). Molecular docking analysis revealed strong binding affinities between BBE and key target proteins, including UCP1, PGC-1α, PRDM16, CIDEA, FGF21, and FGFR1c. BBE significantly reduced lipid accumulation in 3T3-L1 cells, upregulated the mRNA expression of Prdm16, Cidea, Ucp1, and Dio2, elevated UCP1 and PGC-1α protein levels, and activated the FGF21/PGC-1α signaling pathway. In HFD-induced mice, BBE administration led to reduced body weight, smaller adipocyte size, increased adipocyte number, and alleviated hepatic steatosis. Furthermore, it lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and levels of triglycerides (TG), while simultaneously increasing concentrations of high-density lipoprotein cholesterol (HDL-C). BBE also improved glucose tolerance, reduced fasting insulin levels, and modulated adipocytokine levels (reduced leptin, increased adiponectin), while promoting browning gene and protein expression. Overall, the combination of berberine and evodiamine mitigates obesity by enhancing browning and activating the FGF21/PGC-1α signaling pathway. Full article

A novel electrochemical sensor (P-g-C₃N₄/MOF-199/CPE) was developed to determine the metformin concentration in pharmaceutical samples. In this sensor, the copper units of MOF-199 of the composite electrode specifically capture metformin molecules so that the sensing selectivity is remarkably improved. Phosphorus-doped graphitic carbon nitrides (P-g-C₃N₄) further enhance the electrical conductivity and sensitivity of the sensor. The physical and chemical properties of these electrode modifiers were first characterized, followed by electrochemical sensing tests of metformin under different scan rates and pH values. A 39-fold increase in the electrooxidation current of metformin was found in this composite electrode when compared to its bare carbon paste counterpart. A limit of detection (LOD) of 0.15 nM was achieved in the linear sensing range of 0.5 to 1200 nM for metformin. The sensor also showed good reliability and recovery when detecting metformin in pharmaceutical samples. For the first time, we addressed the appearance of adsorption-based peaks in the voltammograms of electrochemical sensors for metformin as a common feature when copper ions are incorporated into the electrode structure. The electrochemical mechanism of metformin was also illustrated by highlighting the hydrolysis of oxime. The nature of all pH-dependent anodic and cathodic peaks in our sensing results confirms the proposed mechanism. Full article

Insulin resistance (IR) disrupts hepatic glucose metabolism and mitochondrial function, which contributes to metabolic disorders. The present study examined the effects of tomatine on glucose metabolism in high-glucose-induced IR hepatocytes and explored its underlying mechanisms using AML12 and HepG2 cell models. The results showed that tomatine did not exhibit cytotoxic effects. Under IR conditions, tomatine dose-dependently improved glucose metabolism by enhancing glucose consumption and restoring the mRNA expression of the glucose transporter Glut2 and gluconeogenesis-related genes (Pepck and G6pase). Mechanistically, tomatine activated the phosphorylation of AMP-activated protein kinase (AMPK) and upregulated the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), reversing the IR-induced suppression of the AMPK/PGC1α pathway. In addition, tomatine enhanced mitochondrial oxidative function by restoring the oxygen consumption rate, increasing ATP production, and upregulating mitochondrial oxidative phosphorylation complex proteins. Both genetic and pharmacological inhibition of AMPK abolished these beneficial effects, confirming its central role in mediating tomatine’s actions. Overall, our findings suggest that tomatine is a promising therapeutic candidate for enhancing hepatic glucose metabolism and mitochondrial function in IR-associated metabolic disorders through AMPK activation. Full article

The successful application of primordial germ cells (PGCs) is an ideal method for generating gene-edited birds. However, barriers to efficient DNA transfection in PGCs lead to low transfection efficiency, limiting the generation of genetically modified chickens. The current study utilized chemical transfection and electroporation methods to determine the optimal transfection conditions for the PGC line under feeder- and serum-free medium. Among the tested methods, the Lonza electroporation system exhibited the highest transduction efficiency, with a previously unreported rate of 71.13 ± 1.26%. Optimal transfection conditions were achieved using 4 µg of DNA and 100 µL of Entranster^TM-E in 1 × 10⁶ PGCs. Furthermore, the optimal electroporation conditions resulted in low cell death and normal expression of pluripotency-related genes, highlighting the low cytotoxicity. The resulting electroporation models were then used to deliver the enhanced green fluorescent protein (EGFP) gene to the Z chromosome with a Cas9-gRNA plasmid, achieving a 7-day insertion efficiency of 14.63 ± 1.07%. Our study highlights the vast potential of electroporation technology for the transfection of PGCs. Full article

Goats are widely recognized for their adaptability and resource efficiency, making them an excellent choice for sustainable farming. However, the Hainan Black goat (HNBG), a vital breed in southern China’s tropical regions, faces significant challenges that threaten its productivity and economic viability. Specifically, young HNBGs exhibit stunted growth and poor muscle development, indicating the breed may have more genetic defects that cause the poor phenotypes. The FNDC5 gene, which encodes the protein irisin, plays a key role in promoting mitochondrial biogenesis and oxidative metabolism by activating critical signaling molecules such as PGC-1α, thereby enhancing muscle endurance and metabolic efficiency. This study aimed to investigate the impact of missense mutations in the FNDC5 gene on growth and meat quality traits in HNBGs. We sequenced a population of HNBGs and identified three SNPs that could lead to amino acid substitutions. Notably, SNP1 (p.119A/V) and SNP2 (p.135R/H) showed strong linkage. Predictions on the structural effects of these mutations indicated that SNP1 (p.119A/V) and SNP3 (p.170W/G) could alter the secondary structure of the FNDC5 protein. Association analyses revealed that SNP1 (p.119A/V) and SNP2 (p.135R/H) were significantly associated with morphometric traits and meat quality. The phenotypic values of SNP1 and SNP2 co-mutants were significantly lower than those of other combined genotypes. Furthermore, gene expression levels of FNDC5 varied notably across individuals with different SNP1 genotypes. These findings suggest that FNDC5-SNP1 (p.119A/V) could serve as a promising genetic marker for selecting HNBGs with improved growth and muscle development, offering a potential pathway for enhancing key economic traits in this breed. Full article

Pyranoanthocyanins exhibit greater bioactivity compared to monomeric anthocyanins, yet the lipid-lowering effects of pyranoanthocyanin Vitisin A, a primary derivative found in aged red wines, have not been extensively studied in vivo. This study evaluated the triglyceride-lowering effects of Vitisin A and its anthocyanin counterpart Cyanidin-3-O-glucoside (C3G) in both free fatty acid -induced HepG2 cells and high-fat diet-fed ApoE^-/- mice, with a focus on their roles in lipid metabolism. In vitro, Vitisin A significantly reduced triglyceride levels and lipid accumulation in HepG2 cells compared to C3G at equivalent concentrate. In vivo, dietary supplementation with 100 mg/kg of Vitisin A reduced body weight gain and plasma triglyceride levels by 19.6% and 29.5%, respectively, whereas no significant effects were observed with C3G. Mechanistically, Vitisin A markedly inhibited hepatic de novo lipogenesis (DNL) by activating the AMPK/ACC signaling pathway and downregulating FASN expression. Concurrently, Vitisin A enhanced fatty acid β-oxidation more robustly than C3G by upregulating CPT-1A via AMPK/SIRT1/PGC-1α and PPAR-α/PGC-1α pathways. Both Vitisin A and C3G driving peroxisomal β-oxidation of very-long-chain fatty acids. In summary, Vitisin A demonstrated superior triglyceride-lowering effects compared to C3G, primarily through dual mechanisms of inhibiting hepatic DNL and enhancing fatty acid β-oxidation. Full article

Metabolic syndrome (MetS) can contribute to a chronic ischemia-relative overactive bladder (OAB). Using fructose-fed rats (FFRs), a rat model of MetS, we investigated the effects of tadalafil (a phosphodiesterase-5 inhibitor) on MetS-associated chronic bladder ischemia and bladder overactivity. Phenotypes of the OAB, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with reduced bladder blood perfusion (in empty bladders) via laser color Doppler imaging and elevated serum nitrite levels, suggesting chronic ischemia-related bladder dysfunction. Treatment with tadalafil (2 mg/kg) promoted pelvic angiogenesis, as shown by magnetic resonance imaging, and increased VEGF and p-eNOS overexpression in the bladder. This treatment restored bladder perfusion and alleviated bladder overactivity without significantly altering most MetS parameters. At the molecular level, FFRs exhibited increased ischemia markers (NGF, HIF-2α, and AMPK-α2) and decreased p-AMPK-α2, along with elevated proinflammatory mediators (ICAM-1, nuclear NF-κB, COX-2, IL-1β, IL-6, and TNF-α), enhanced mitochondria biogenesis (PGC-1α, TFAM, and mitochondria DNA copy number), oxidative stress (decreased nuclear NRF2, increase MnSOD and 8-OHdG staining), and tissue fibrosis (increased TGF-β1, collagen I, and fibronectin). Tadalafil treatment improved these effects. Together, these findings suggest that tadalafil may promote VEGF-associated angiogenesis, enhance p-eNOS staining in the bladder vasculature, normalize bladder perfusion in microcirculation, and reduce serum nitrite levels. Consequently, tadalafil mitigates the adverse effects of chronic ischemia/hypoxia, improving bladder overactivity. We elucidated the mechanisms underlying the tadalafil-mediated amelioration of MetS-associated OAB symptoms. Full article

Net ecosystem productivity (NEP) is an extremely important flux for terrestrial ecosystems, indicating the value of net ecosystem exchange (NEE) between terrestrial ecosystems and the atmosphere, excluding carbon fluxes from disturbances. Leveraging flux network NEE annual measurements, this study focuses on upscaling the tower-based NEP to a global 250 m resolution dataset with flux site distribution considerations. Firstly, the data augmentation method was presented to address issues related to the uneven spatial distribution of flux sites. Secondly, a random forest model was developed for NEP estimation using the optimized tower-based NEP and remotely sensed and meteorological gridded sample sets, giving an R² value of 0.73 and an RMSE value of 149.83 gC m⁻² yr⁻¹. Finally, a global NEP product at a 250 m resolution was generated (2001–2022, average 13.79 PgC yr⁻¹) and evaluated. In summary, we present a solution to the overestimation of global NEP by data-driven methods, producing a long-time-series, high-resolution NEP dataset that is more comparable to atmospheric inversion results. This dataset enhances comparability with atmospheric inversion results, thereby boosting our confidence in conducting a consistency analysis of terrestrial carbon sinks across different methods within the framework. Full article

Retinoic acid (RA) plays a critical role in initiating meiosis in primordial germ cells (PGC), yet the specific mechanisms of its interaction with PGC remain unclear. In this study, we used an in vitro feeder-free culture system with chicken PGC as a model to explore the mechanisms by which RA induces the entry of PGC into meiosis. Results demonstrated that exogenous RA treatment altered the cell cycle distribution of PGC, significantly increasing the proportion of cells in the G1 phase and decreasing those in the G2 phase, suggesting that RA may promote the transition of PGC from proliferation to differentiation. Giemsa staining further revealed that chromosomes in a subset of RA-treated PGC exhibited meiotic characteristics. Through combined RNA-seq and ATAC-seq analyses, we identified that CYP26A1, a gene involved in RA degradation, was significantly upregulated in the RA-treated group, with enhanced accessibility in its chromatin regions. This finding suggests a robust mechanism for self-regulation of RA levels within PGC, indicating that CYP26A1 may play a pivotal role in the degradation of exogenous RA in chicken PGC. This study elucidated the effects of RA on chicken PGC and provided new insights into the role of RA in germ cell differentiation. Full article

Background/Objectives: The PPARGC1A gene, encoding the PGC-1α protein, is a critical regulator of energy metabolism, influencing mitochondrial biogenesis, fatty acid oxidation, and carbohydrate metabolism. This narrative review aims to evaluate the role of the PPARGC1A gene, with a specific focus on the c.1444G<A polymorphism (rs8192678), in sports performance, including its impact on aerobic capacity, muscle adaptation, and its potential implications for metabolic health. Methods: A comprehensive literature search was conducted using databases such as PubMed, Scopus, Science Direct, and Web of Science, following PRISMA guidelines. Studies investigating the rs8192678 polymorphism in athletes, its relationship with physical performance, and its broader metabolic effects were included. Data were synthesized qualitatively, and heterogeneity among findings was assessed. The rs8192678 polymorphism influences sports performance differently. Results: the G allele is associated with enhanced mitochondrial efficiency, higher aerobic capacity, and a greater proportion of fatigue-resistant type I muscle fibers, benefiting endurance sports like cycling and triathlon. Conversely, the A allele correlates with reduced mitochondrial biogenesis and oxidative capacity, potentially impairing endurance but showing possible utility in strength-based sports. Furthermore, the A allele is linked to increased risks of metabolic conditions, including type 2 diabetes and obesity. Discrepancies in results highlight the influence of genetic, environmental, and training interactions. Conclusions: the PPARGC1A rs8192678 polymorphism plays a significant role in athletic performance and metabolic regulation. While the G allele confers advantages in endurance sports, the A allele presents mixed implications for strength and metabolic health. These findings support the potential for genetic profiling in personalized training and health interventions but emphasize the need for further research to clarify genotype-environment interactions. Full article

Background/Objectives: Biogenic volatile organic compounds (BVOCs), extensively studied in terrestrial plants with global emissions around 1 PgC yr⁻¹, are also produced by marine organisms. However, benthic species, especially seagrasses, are understudied despite their global distribution (177,000–600,000 km²). This study aims to examine BVOC emissions from key Mediterranean seagrass species (Cymodocea nodosa, Posidonia oceanica, Zostera noltei, and Zostera marina) in marine and coastal lagoon environments. Methods: BVOCs were collected using headspace solid-phase microextraction (HS-SPME) using divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fibers and analyzed by gas chromatography–mass spectrometry (GC-MS). Results: An important chemical diversity was found with a total of 92 volatile compounds (61 for Z. noltei, 59 for C. nodosa, 55 for P. oceanica, and 51 for Z. marina), from different biosynthetic pathways (e.g., terpenoids, benzenoids, and fatty acid derivatives) and with several types of chemical functions (e.g., alkanes, esters, aldehydes, and ketones) or heteroatoms (e.g., sulfur). No differences in chemical richness or diversity of compounds were observed between species. The four species shared 29 compounds enabling us to establish a specific chemical footprint for Mediterranean marine plants, including compounds like benzaldehyde, benzeneacetaldehyde, 8-heptadecene, heneicosane, heptadecane, nonadecane, octadecane, pentadecane, tetradecane, and tridecanal. PLS-DA and Heatmap show that the four species presented significantly different chemical profiles. The major compounds per species in relative abundance were isopropyl myristate for C. nodosa (25.6%), DMS for P. oceanica (39.3%), pentadecane for Z. marina (42.9%), and heptadecane for Z. noltei (46%). Conclusions: These results highlight the potential of BVOCs’ emission from seagrass ecosystems and reveal species-specific chemical markers. Full article