Search Results (1,798)

Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we evaluated whether kaempferol (KAM), a dietary flavonoid, offers neuroprotection in a rat BCCAO/R model. Adult Wistar rats were gavage fed a single dose of KAM (40 mg) six hours before surgery. Comprehensive lipidomic and molecular analyses were conducted on samples from the frontal and temporal-occipital cortices, as well as the plasma. In the frontal cortex, KAM elevated anti-inflammatory N-acylethanolamines palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) and reduced oxidized arachidonic acid metabolites. KAM also downregulated cyclooxygenase- 2 (COX-2) protein and selectively decreased the endocannabinoid 2-arachidonoylglycerol (2-AG), showing a shift in AA metabolism. These molecular changes correlated with increased levels of peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of both nuclear and membrane-bound anti-inflammatory pathways. No significant changes were observed in the temporal-occipital cortex. In plasma, DHAEA levels increased similarly to those in the cortex. However, rises in PEA and OEA were detected only in sham-operated KAM-treated animals, suggesting possible central redistribution under hypoperfusion/reperfusion stress. In summary, these findings demonstrate that KAM exerts dual anti-inflammatory effects by inhibiting COX-2-mediated prostanoid synthesis and promoting PPARα-driven lipid signaling. This dual mechanism highlights the potential of KAM as a dietary intervention to reduce neuroinflammation associated with hypoperfusion–reperfusion challenges. Full article

Background: Cardiometabolic syndromes, including diabetes, obesity, and metabolic syndrome, significantly contribute to cardiovascular fibrosis, a major driver of heart failure. Non-coding RNAs (ncRNAs)—notably microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—have emerged as critical epigenetic regulators of fibrotic remodeling. Recent studies indicate that widely used metabolic modulators can influence ncRNA expression, potentially impacting on cardiovascular fibrosis. This review synthesizes evidence on the interplay between metabolic therapies and ncRNA regulation, with emphasis on therapeutic and biomarker potential of miRNAs. Methods: A literature search was manually curated and conducted on PubMed for studies published mainly in the last decade and evaluating the effects of metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, glucagon-like peptide 1 (GLP-1) receptor agonists, and fatty acid oxidation inhibitors on ncRNA expression in the context of cardiovascular fibrosis. Data from in vitro, in vivo, and clinical studies were extracted and categorized by drug class, ncRNA target, and functional outcomes. Results: Several metabolic modulators specifically downregulate pro-fibrotic (miR-21, miR-92, H19, and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)) and upregulate anti-fibrotic ncRNAs (miR-29, miR-133a, miR-711, miR-133a, miR-30a and miR-200 family). This results in global attenuation of the transforming growth factor- beta (TGF-β) signaling, which limits extracellular matrix (ECM) accumulation thus improving myocardial compliance. Across drug classes, changes in ncRNA profiles paralleled improvements in fibrosis-related endpoints. Conclusions: Metabolic modulators exert anti-fibrotic effects partly through ncRNA regulation, offering novel therapeutic strategies and potential biomarkers for cardiovascular fibrosis in cardiometabolic disease. Targeting metabolic–ncRNA crosstalk may enable more precise and synergistic interventions for preventing or reversing pathological remodeling. Full article

Obesity, characterized by the accumulation of excess adipocytes, is a significant risk factor for type 2 diabetes and non-alcoholic fatty liver disease. Medicinal plants, including Hibiscus sabdariffa, have been traditionally employed to prevent or treat conditions such as obesity and inflammation due to their safety profile and minimal side effects during long-term use. However, the anti-obesity potential of Hibiscus syriacus, a taxonomically distinct species within the same genus, remains unexplored. In this study, we screened 181 varieties of H. syriacus buds for anti-obesity effects and identified the water extract of the ‘Pyeonghwa’ bud (HPWE) as a potent inhibitor of adipogenesis. Using 3T3-L1 murine pre-adipocyte cells, we demonstrated that HPWE significantly reduced lipid accumulation without inducing cytotoxicity. Mechanistically, HPWE downregulated the expression of key adipogenic signaling proteins and transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), which serve as molecular markers of adipogenesis. Additionally, in vivo experiments employing a high-fat-diet-induced obesity mouse model using C57BL/6 species confirmed the anti-obesity effects of HPWE. Collectively, these findings suggest that HPWE represents a promising candidate for the prevention of obesity. Full article

Neuropeptide Q (spexin, spx) is a pleiotropic signalling molecule that regulates appetite and metabolism primarily via activation of galanin and melanocortin receptors. Here, we cloned the open reading frame (ORF) of spx from Siniperca chuatsi (Scspx), characterised its spatiotemporal expression, elucidated spx regulatory features during starvation and feed adaptation, and identified SPX-interacting proteins using glutathione S-transferase pull-down and mass spectrometry. The Scspx ORF was 312 bp, encoding 103 amino acids. The predominant expression of spx was found in the liver of feed-trained S. chuatsi, where it was 17.36-fold greater than in muscle. During fasting (0, 3, 5, and 7 d), spx expression in the muscle, liver, and intestine initially increased and then declined, whereas brain and stomach tissues exhibited the opposite tendency. Compared to the smallest individuals, hepatic and brain spx expression was substantially lower in the largest individuals, whereas stomach expression was higher (p < 0.05). Fatty acid binding protein 2 was identified as a novel SPX-interacting partner, implicating SPX in feed adaptation through lipid metabolic regulation via the peroxisome proliferator-activated receptor signalling pathway. Our results provide the first evidence of a direct SPX-FABP2 interaction in fish, pointing to a coordinated role in downstream gene regulation. This work hereby uncovers a novel regulatory axis within the piscine energy metabolism network. These findings provide new insight into the regulatory role of SPX in feed adaptation in S. chuatsi, offering a foundation for genetic analysis. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disorder where age, genetic factors and sleep disturbance significantly influence disease risk. Recent genome-wide association studies identified a C/T missense variant (rs141749679) in the sortilin (SORT1) gene linked to heightened AD risk, revealing SORT1’s role as a key player in the disease’s pathophysiology. This type I membrane glycoprotein is implicated in amyloid β (Aβ) accumulation and associated lipid dysregulation, particularly through its interaction with apolipoprotein E (ApoE). SORT1 facilitates the uptake of ApoE-bound polyunsaturated fatty acids (PUFAs), conversion to endocannabinoids (eCBs), and the regulation of anti-inflammatory pathways via peroxisome proliferator-activated receptors (PPARs). Notably, this neuroprotective signaling is contingent on the APOE allele, exhibiting functionality in presence of ApoE3 but disrupted with ApoE4. Additionally, the brain-type fatty acid binding protein, FABP7, mediates this signaling cascade, emphasizing its role in neuron-glia communication. FABP7 is known to regulate sleep across species and binds PUFAs and eCBs. Therefore, dysfunction of the ApoE-SORT1-FABP7 axis may underlie the neuroprotective loss observed in AD, linking sleep disruption and lipid homeostasis to disease progression. This perspective aims to elucidate the intricate neural-glial mechanisms governing the ApoE-SORT1-FABP7 interaction and their implications for targeting therapeutic interventions in Alzheimer’s disease. Full article

The aim of the present study is to evaluate the impact of chromium (Cr) supplementation on glucose and lipid metabolism in breast muscle in broilers under heat stress. A total of 220 day-old broiler chicks were reared in cages. At 29 days old, 180 birds were randomly assigned to three treatments (0, 400, and 800 µg Cr/kg, as chromium picolinate) and transferred to climate chambers (31 ± 1 °C, 60 ± 7% humidity) for 14 days. Growth performance, carcass traits, serum biochemical indices, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), as well as muscle metabolomic profiles and gene expression related to energy and lipid metabolism were analyzed. The results showed that, compared with the heat stress group, the groups supplemented with 400 and 800 µg Cr/kg showed higher dry matter intake and average daily gain, breast muscle ratio, and lower feed conversion ratio and abdominal fat ratio; chickens supplemented with 400 and 800 µg Cr/kg showed significantly lower serum corticosterone (CORT), free fatty acids, and cholesterol levels compared with the heat stress (HS) group (p < 0.05). Fasting blood glucose and HOMA-IR were also significantly reduced, while fasting insulin was significantly increased in the Cr-supplemented groups (p < 0.05). Metabolomic analysis revealed that Cr supplementation regulated lipid and amino acid metabolism by altering key metabolites such as citric acid, L-glutamine, and L-proline, and modulating pathways including alanine, aspartate, and glutamate metabolism, and glycerophospholipid metabolism. Furthermore, Cr supplementation significantly upregulated the expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 α (PGC-1α), ATP Binding Cassette Subfamily A Member 1 (ABCA1), Peroxisome Proliferator-Activated Receptor α (PPARα), and ATP Binding Cassette Subfamily G Member 1 (ABCG1) in both the hepatic and muscle tissue. This paper suggested that chromium supplementation may enhance energy metabolism and lipid transport like the findings of our study suggested. Full article

To assess the influence of dietary bile acid (BA) on the phenotype associated with hepatic lipid metabolism and its regulation of lipid homeostasis in gibel carp (Carassius auratus gibelio) under high-fat diet (HFD) conditions, five HFDs were designed using soybean oil (SO) as the single lipid source and supplemented with 0, 200, 400, 600, and 800 mg/kg BA (designated as BA0, BA200, BA400, BA600, and BA800, respectively). Juvenile fish (32.37 ± 0.13 g) were fed five BA-added HFDs (12% SO) for 8 weeks. Considerably lower levels of aspartate transaminase, alanine aminotransferase, low-density lipoprotein, triglyceride, and total cholesterol in the serum were observed in gibel carp fed with HFDs with 400–600 mg/kg BA (p < 0.05). The hepatocytes of the BA400 and BA600 groups were intact without abnormal architecture or histopathological changes, compared to other groups. The presence of most genes related to fatty acid biosynthesis decreased significantly with the addition of 400–600 mg/kg BA (p < 0.05), while the gene expressions of hormone-sensitive lipase, adiponectin receptor 2, and peroxisome proliferator-activated receptor α were variably up-regulated, along with the elevation of dietary BA (p < 0.05). Critical genes involved in bile acid and cholesterol synthesis were obviously down-regulated in gibel carp receiving 600–800 mg/kg dietary BA (p < 0.05), despite the sterol 27-hydroxylase (cyp27a1) gene in the BA800 group (p < 0.05). Moreover, hepatopancreas from the BA0 and BA600 groups were isolated for transcriptome sequencing, identifying 7040 differentially expressed genes (DEGs). The enriched KEGG pathways of DEGs mainly included steroid biosynthesis, protein digestion and absorption, etc. Seven randomly selected DEGs were validated using qRT-PCR and were in agreement with the RNA-seq results. Consequently, the appropriate supplementation of dietary BA for juvenile gibel carp is recommended at doses of 400–600 mg/kg in SO-based HFDs, which could contribute to the amelioration of HFD-induced excessive fat deposition in the hepatopancreas of gibel carp by both inhibiting fatty acid intake, biosynthesis, and steroid production and enhancing lipid decomposition. The findings may elucidate the physiological role of exogenous BA in fish and its underlying mechanism, providing references for the reasonable application of BA in aquafeeds and the prevention of HFD-induced metabolic dysfunction in fish. Full article

This review of thiazolidinedione or glitazone, which have a five-membered heterocyclic ring C₃NS, shows their versatile properties in terms of pharmacological actions such as antimicrobial, antifungal, insecticidal, pesticidal, antidiabetic, anti-inflammatory, anti-proliferative, anti-neurotoxicity, anticonvulsant, anti-thyroidal, and anti-tubercular uses. While having a wide range of biological activities, the TZDs mainly act via binding to the peroxisome proliferator-activated receptor (PPAR) members. PPAR-γ are ligand-activated transcription factors, which are members of the nuclear hormone receptors group. Activations of PPAR-γ regulate cell proliferation and differentiation, glucose homeostasis, apoptosis, lipid metabolism, and inflammatory responses. This review explores the synthesis of a thiazolidinedione and its derivatives, focusing on their pharmacological profiles and antidiabetic activity. It highlights the benefits of synthesis, reaction profiles, and catalyst recovery, which may encourage further investigation into these scaffolds by researchers. Based on synthesized derivatives, some glimpses of the structure–activity relationships of some compounds have been compiled. All the synthesized derivatives have been reviewed concerning their standard drugs already available and concluded with the highly or moderately active synthesized derivatives of thiazolidinedione. The data for this review was collected by an extensive review of current scientific literature, including on the synthesis, biological evaluation, SAR, and patents (2015–25). Full article

Objectives: This study focuses on the regulatory mechanism of Schisandrin B (Sch B) on the lipid metabolism and apoptosis of AML-12 liver cells, with a particular emphasis on its potential therapeutic effect and mechanism of action in preventing and treating metabolic-associated fatty liver disease (MAFLD) by activating the PPARγ signaling pathway. Methods: An MAFLD cell model was established by inducing AML-12 cells with a mixture of oleic acid (OA) and palmitic acid (PA) (2:1). AML-12 cells were divided into a control group, a model group, and 20 μM and 40 μM Sch B groups. The cells were lysed and prepared into the cell suspension, then the cell suspension was centrifuged to obtain its supernatant, and the levels of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the supernatant were detected according to the instructions of the kits. Effects of Sch B on the pathological changes of AML-12 cells were observed by Oil Red O staining. The key targets were screened through network pharmacology, and relevant targets were verified through molecular docking simulation. The activity of PPARγ was detected using a dual luciferase reporter plasmid, and the level of cell apoptosis was detected using the Annexin V-FITC/PI double staining method. The Western blot method was used to analyze the expression of genes related to lipid metabolism and apoptosis pathways. Results: Sch B could regulate lipid metabolism disorders in OA+PA-induced MAFLD cell model. The activation of PPARγ-PCK1/Aspase is a key step in the action of Sch B, which can effectively block fatty acid synthesis, improve fatty acid oxidation, and reduce lipid droplet aggregation in liver cells, thereby alleviating lipid metabolism abnormalities in the MAFLD cell model and inhibiting cell apoptosis. Conclusions: This finding may lay an important theoretical foundation and open a new research direction for the deep development and application of Schisandra chinensis. Full article

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by cholestasis and progressive fibrosis. While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30–40% of patients have an inadequate biochemical response, increasing the risk of disease progression. Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was the first second-line agent approved by the only Food and Drug Administration (FDA) and has demonstrated moderate biochemical efficacy but limited tolerability due to dose-dependent pruritus and safety concerns in cirrhosis. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies’ mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research into long-term clinical outcomes. Full article

Mitochondria are increasingly recognized as important contributors to immune function, in addition to energy production. They exert this influence through modulation of various signaling pathways that regulate cellular metabolism and immune function in response to pathogens. Peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PGC-1α) is the primary transcription factor and regulator involved in mitochondrial biogenesis. Long known to be involved in immune function, zinc (Zn) is also required for proper mitochondrial function. It is increasingly recognized that many cellular immunometabolic activities are also Zn-dependent. Taken together, we investigated the role of Zn deficiency, both dietary and genetically induced, and Zn supplementation in PGC-1α-mediated macrophage mitochondrial biogenesis and immune function following infection with Mycobacterium avium complex (MAC). Our novel findings show that Zn is an important regulator of PGC-1α, TFAM and mitochondrial biogenesis, leading to enhanced bacterial phagocytosis and bacterial killing in macrophages. Mechanistically, we show that the Zn importer ZIP8 (Zrt/Irt-like protein) orchestrates Zn-mediated effects on PGC-1α and mitochondrial function. Taken together, defective Zn biodistribution may increase susceptibility to infection, whereas Zn supplementation may provide a tractable host-directed therapy to enhance the innate immune response in patients vulnerable to MAC infection. Full article

Background/Objectives: Most genes involved in the pathogenesis of Metabolic Syndrome (MS) and Type 2 Diabetes Mellitus (T2DM) are regulated by peroxisome proliferator-activated receptors (PPARs), which modulate the production of pro-inflammatory cytokines, with interleukin-6 (IL-6) playing a crucial role. The associations of single-nucleotide polymorphisms (SNPs) with MS and T2DM remain uncertain across populations. Therefore, we aimed to investigate the associations of PPAR-related SNPs in IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 with MS and T2DM clinical features. Methods: Polymorphism analysis of IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 genes was performed on isolated DNA from individuals diagnosed with T2DM and from healthy controls using real-time polymerase chain reaction (qPCR). Results: The IL-6-174G/C polymorphism shows that the CC genotype is associated with higher MS risk, whereas the GG genotype appears protective against metabolic disturbances. When the IL6 CC genotype is combined with ADIPOR2 GA or ADIPOR2 219 A/T, hyperglycemia is 1.3 times more frequent than with other IL6/ADIPOR2 genotype combinations. Conclusions: To develop informative genetic risk scores, future studies should include additional polymorphisms in key immune–metabolic pathway genes, such as AP-1, NF-κB, and FFAs. Full article

Background: Multiple sclerosis is a multifactorial neurodegenerative disease characterized by autoimmune and inflammatory processes. Despite advancements in disease-modifying therapies, multiple sclerosis remains challenging due to its complex pathophysiology and variable clinical presentation. Current therapies focus on managing inflammation and promoting immunosuppression but do not achieve complete symptom regression or enhance remyelination. Emerging therapies, such as Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonists and Bruton tyrosine kinase (BTK) inhibitors, show promise in modulating inflammation and targeting immune cells. Innovative approaches like human fetal neural precursor cells (hfPNCs) and mesenchymal stem cell transplantation are being explored to reduce neural inflammation and improve neuroprotection. Early diagnosis and intervention are crucial for managing multiple sclerosis effectively and preventing progression to severe forms and permanent disability. Therapeutic education for individuals with multiple sclerosis and their caregivers is essential, emphasizing the need for clear, reliable information to support disease management and improve quality of life. Objectives: This review provides an up-to-date overview of multiple sclerosis pathophysiology, current treatments, and emerging therapies, aiming to enhance the knowledge base of healthcare professionals and researchers, facilitating informed decision-making and contributing to ongoing research efforts. Full article

Temporal lobe epilepsy (TLE) remains pharmacoresistant in 30–40% of patients. Peroxisome proliferator-activated receptor alpha (PPARα) agonists like fenofibrate exhibit anti-inflammatory and neuroprotective properties, but their region-specific effects during epileptogenesis and on behavioral comorbidities are unknown. We investigated fenofibrate (100 mg/kg, 7 days) in the lithium-pilocarpine rat model during the latent phase. Fenofibrate (1) reduced anxiety-like behaviors and improved exploratory deficits; (2) decreased plasma short-chain fatty acids (butyric, pentanoic, hexanoic acids); (3) exerted region-specific modulation of glutamate receptors: restored N-methyl-D-aspartate receptor (NMDAR)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit gene expression in temporal cortex but failed to reverse and further exacerbated the downregulation of AMPAR subunits in the dorsal hippocampus; (4) prevented the upregulation of cortical neuroinflammation markers (reduced Nlrp3, Il1rn); and (5) enhanced the A2 astrocyte marker Ptx3 in the hippocampus while reducing the M2 microglial marker Arg1 in the temporal cortex. No effects on astrogliosis (Gfap), microgliosis (Aif1), or trophic factors (Bdnf, Tgfb1) were observed. This first comprehensive study demonstrates that fenofibrate differentially modulates neuroinflammation and synaptic plasticity across brain regions during epileptogenesis, providing behavioral benefits but highlighting potential hippocampal drawbacks. Its PPARα-mediated actions support further investigation as a complementary strategy for TLE, pending optimization of dosing/timing to mitigate regional disparities. Full article

Background/Objectives: This systematic review aimed to gather the most recent evidence regarding the link between genetic polymorphisms and physical performance in team sports, with a focus on the practical utility of this information for athlete selection, training personalization, and injury prevention. Methods: Sixteen studies published between 2018 and 2025 were analyzed and selected from six international databases, in accordance with the PRISMA guideline. Only English-language studies were included, which evaluated active athletes in team sports and investigated associations between genetic variations, such as Actinin Alpha 3 (ACTN3 R577X), Angiotensin I Converting Enzyme (ACE I/D), Peroxisome Proliferator-Activated Receptor Alpha (PPARA), Interleukin 6 (IL6), and Nitric Oxide Synthase 3 (NOS3), and physical performance parameters. The methodological quality of the studies was assessed using the Q-Genie tool, with all studies scoring over 45 across all 11 items, indicating high quality. Results: The ACTN3 and ACE genes stood out due to their consistent association with traits such as strength, speed, endurance, and recovery capacity. Other genes, such as PPARA, Fatty Acid Amide Hydrolase (FAAH), Angiotensinogen (AGT), and NOS3, complemented this genetic profile by being involved in the regulation of energy metabolism and injury predisposition. An increasing number of studies have begun to adopt cumulative genotype scores, suggesting a shift from a monogenic approach to complex predictive models. Conclusions: The integration of genetic profiling into the evaluation and management of athletes in team sports is becoming increasingly relevant. Although current evidence supports the applicability of these markers, robust future research conducted under standardized conditions is necessary to validate their use in sports practice and to ensure sound ethical standards. Full article