Search Results (1,149)

Progression to fibrosis is a major complication of chronic kidney disease (CKD) in obesity, type 2 diabetes, hypertension, and metabolic syndrome, yet effective antifibrotic therapies remain limited. Here, we review how disordered renal energy metabolism—ectopic lipid accumulation, impaired fatty acid oxidation (FAO), and a compensatory shift toward glycolysis—drives tubulointerstitial fibrosis in fatty kidney disease. Lipid overload in tubular, glomerular, and vascular cells arises from increased uptake via scavenger and lipoprotein receptors, enhanced lipogenesis, and reduced lipid catabolism and clearance. Spatial lipidomic studies further reveal nephron-segment-specific lipid signatures and obesity-associated oxidized phospholipids linked to glomerular inflammation. Lipotoxicity, mitochondrial damage, and associated innate-immune signaling, ferroptosis, cellular senescence, and adipose-derived mediators (including leptin, adiponectin, and a locally active renin–angiotensin system) converge on myofibroblast activation from pericytes, fibroblasts, and other resident cells. We discuss established and emerging therapies targeting this metabolic axis—peroxisome proliferator-activated receptor-α (PPARα) modulators, sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and the mineralocorticoid receptor antagonist finerenone—and propose that restoring metabolic flexibility, by rescuing FAO while limiting maladaptive glycolysis, offers a promising disease-modifying strategy for fatty kidney disease. Full article

Background: Kidney disorders are strongly related to metabolic disturbances, including obesity and type 2 diabetes. Excessive intake of sugar and saturated fats promotes lipid accumulation, cellular energy issues and inflammatory responses. Cannabigerol (CBG), a non-psychotropic phytocannabinoid, has recently gained attention for its metabolic, anti-inflammatory and potential protective properties. Methods: The present study investigated the effect of two weeks of CBG administration (last 14 days of the experiment) on fatty acid (FA) composition, FA metabolic pathways and FA transporters in rats subjected to a high-fat high-sucrose diet (HFHS) for 6 weeks. Male Wistar rats were divided into four groups: Control, CBG, HFHS, and HFHS+CBG. Kidney tissue and urine samples were analyzed by gas–liquid chromatography (GLC) for lipid fractions and FA profiles, while protein expression of FA transporters and metabolic enzymes was assessed by immunoblotting. Polysaccharides and collagen fibers were visualized using Periodic Acid-Schiff (PAS) and AZAN staining, respectively. ELISA and colorimetric kits were used to measure urinary albumin and creatinine contents. Results: HFHS feeding altered renal lipid homeostasis, increasing saturated and monounsaturated fatty acids (SFA and MUFA, respectively) levels and affecting desaturation and elongation ratios. CBG supplementation affected renal lipid metabolism by lowering triacylglycerol (TAG) accumulation, restoring polyunsaturated fatty acids (PUFA) in phospholipid (PL) and altering FA ratios, suggesting an improvement in lipid balance. CBG also increased the expression of carnitine palmitoyltransferase 1 (CPT1) and lipoprotein lipase (LPL) and decreased the expression of stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase (FAS), suggesting a shift toward enhanced FA oxidation and reduced lipogenesis. Conclusions: Overall, CBG exerted good effects on renal lipid metabolism and may mitigate early lipid-mediated injury associated with metabolic kidney disorders. Full article

Background/Objectives: Obesity-related insulin resistance is accompanied by chronic low-grade inflammation, but the extent to which weight loss modifies circulating cytokines in a sex-specific manner remains insufficiently understood. The aim of this study was to assess sex-specific cytokine responses and metabolic adaptation in adults with obesity and insulin resistance following a six-month weight-reduction program (WRP). Methods: Thirty-six participants (24 women and 12 men) with a value of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2 underwent an individualized low-calorie diet combined with moderate physical activity and health education. Anthropometric, body composition, biochemical, oxidative stress, and cytokine parameters were evaluated before and after the intervention. Results: Both women and men showed significant reductions in body mass, Body Mass Index (BMI), waist circumference, visceral fat area (VFA), body fat mass (BFM), fasting glucose, HOMA-IR, modified Atherogenic Index of Plasma (new-AIP), malondialdehyde (MDA), and Oxidative Stress Index (OSI). Women additionally showed significant decreases in fat-free mass (FFM), skeletal-muscle mass (SMM), total body water (TBW), glycated hemoglobin A_1c (HbA1c), and triacylglycerols, whereas cholesterol in high-density lipoproteins (HDL-C) increased significantly in men. Cytokine changes were selective rather than uniform. Interleukin-1 receptor antagonist (IL-1ra), Interleukin 6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α) decreased in both women and men. In sex-stratified analyses, IL-1β decreased significantly only in women, whereas IL-7 decreased significantly only in men. ClinicalTrials.gov Registration: [NCT07645105] (retrospectively registered on [11 June 2026]). Conclusions: A 6-month lifestyle-based weight-reduction program in adults with overweight or obesity and insulin resistance was associated with metabolic improvement, reduced oxidative stress, and partial attenuation of obesity-related low-grade inflammation. The observed cytokine and metabolic changes suggest sex-related patterns of immunometabolic adaptation to weight reduction. However, these findings should be interpreted cautiously because of the relatively small sex-stratified subgroups and the number of cytokine endpoints analyzed, and they require confirmation in larger, sex-balanced studies. Full article

Insulin resistance (IR) is traditionally viewed within the context of type 2 diabetes. However, it increasingly appears to represent a broader systemic metabolic risk state with potential relevance for carcinogenesis. Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis. At the same time, IR is closely linked to oxidative stress, chronic low-grade inflammation, and epigenetic alterations, together shaping a tumor-promoting microenvironment. Epidemiological studies report consistent associations between IR and increased cancer risk, particularly for endometrial, liver, and colorectal cancers. Yet causality remains uncertain and likely varies by tumor type. Notably, metabolic dysfunction may also occur in individuals with normal body mass index (BMI), underscoring the limitations of BMI-based risk assessment. Unlike previous reviews that primarily focused on individual mechanisms or epidemiological associations, this review examines IR as a systemic metabolic risk state by integrating molecular, epidemiological, biomarker-based, and prevention-oriented perspectives. Particular emphasis is placed on strategies for earlier risk identification using integrated biomarker approaches, including fasting glucose, homeostatic model assessment of insulin resistance, triglyceride-to-high-density lipoprotein ratio, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Emerging tools such as continuous glucose monitoring and hepatokine profiling may further refine risk detection. Sustained lifestyle modification—diet, physical activity, sleep, and stress regulation—remains central to prevention. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification. Full article

Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization—characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension—is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde/oscillatory shear stress. With a central focus on the axis of “exercise-shear stress-glycocalyx-cytoskeleton/junction-permeability-plaque stability,” this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2), thereby stabilizing adherens/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation–matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites. Full article

Despite increasing efforts to improve cardiovascular disease (CVD) risk evaluation and management, it remains a leading cause of mortality and morbidity worldwide. This has driven interest in high-density lipoprotein (HDL)-related biomarkers as indicators of oxidative stress and atherogenic processes not fully captured by traditional lipid measurements. In this study, we examined specific paraoxonase 1 (PON1) activity and its relationship with anthropometric, blood pressure, and lipid metabolism measures in 100 middle-aged Lithuanian individuals at high cardiovascular risk. HDL fractions were isolated using iodixanol-based density gradient centrifugation. PON1 concentration and arylesterase activity were measured, and specific activity was defined as arylesterase activity normalized to PON1 concentration. No significant associations were observed between specific PON1 activity and age, body mass index, waist circumference, blood pressure, smoking status, or statin use. Specific PON1 activity was independently associated with lower risk-weighted apolipoprotein B and lower low-density lipoprotein cholesterol levels. These exploratory findings suggest that higher specific PON1 activity may reflect a less atherogenic lipid profile in individuals at high cardiovascular risk, as indicated by its association with LDL-C and with risk-weighted apolipoprotein B. Because direct oxidative stress and inflammatory markers were not measured, interpretations regarding oxidative burden should be considered indirect and hypothesis-generating. Given the cross-sectional nature of the study and the relatively small sample size, these results should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies in larger populations are needed to confirm these observations. Full article

Lipids play a central role in poultry nutrition by modulating energy utilization, nutrient digestibility, and metabolic processes related to lipid absorption and deposition. This review synthesizes current knowledge on the main dietary lipid sources used in poultry nutrition and their effects on performance, lipid metabolism, and egg yolk fatty acid composition. Conventional lipid sources, including vegetable oils and animal fats, differ in fatty acid profile, degree of saturation, and digestibility, which directly influence metabolic efficiency and productive responses. In addition, the strategic use of lipid sources enables the modulation of fatty acid profiles in poultry products, particularly through the enrichment of polyunsaturated fatty acids such as omega-3. These effects are associated with mechanisms involving lipid digestion, absorption, and hepatic lipoprotein synthesis, which regulate fatty acid deposition in tissues and egg yolks. However, responses to dietary lipids are influenced by factors such as inclusion level, oxidative stability, and lipid composition. Overall, dietary lipid manipulation represents an effective strategy to optimize production efficiency and enhance the nutritional quality of poultry-derived foods. Full article

Cardiovascular diseases (CVDs) continue to pose a key challenge to public health because of their high prevalence, mortality, and disability rates, together with a trend toward younger age at onset. Chronic inflammation and disordered lipid metabolism are key pathological mechanisms underlying the development and progression of CVDs. Although numerous pharmacological agents have been developed to intervene in CVDs, current therapies are still limited by adverse effects, suboptimal efficacy, and insufficient anti-inflammatory properties. Consequently, effective drug-based strategies for the prevention and treatment of certain CVDs are still insufficient. Cluster of differentiation 36 (CD36), a class B scavenger receptor, mediates the recognition and uptake of long-chain fatty acids, oxidized low-density lipoprotein, and other ligands, and is present in diverse tissues and cell types. Accumulating evidence indicates that CD36 plays a critical role in lipid metabolism and inflammatory signalling pathways implicated in CVDs, suggesting that it represents a promising focus for treatment-oriented interventions. This review synthesizes current evidence on the multifaceted roles of CD36 in lipid metabolism dysregulation and inflammation-associated pathways in CVDs and evaluates its potential as a tractable target for disease prevention and management. Full article

Adipose tissue-derived extracellular vesicles (adiposomes) carry a protein cargo that we previously showed differs between obese and lean individuals. In this study, we investigate how adiposomal protein cargo changes in response to sleeve gastrectomy and examine whether these changes are associated with clinical improvements. Twenty-three obese adults underwent pre- and post-bariatric surgery adipose sampling for adiposome isolation and clinical assessments that included vascular and metabolic profiles and inflammatory markers. The adiposomal protein cargo was analyzed via non-targeted proteomics. Differential protein abundance, pathway enrichment, and correlation analyses were assessed. Twelve weeks after bariatric surgery, BMI and fat mass decreased, accompanied by improved glucose and lipid profiles. Inflammatory markers (leptin, IL-6, CRP) also declined, while adiponectin and nitric oxide increased. Adiposomal proteomics identified 287 proteins, with 138 significantly altered. Downregulated proteins included PRDX2, FN1, SERPIND1, and inflammatory mediators; upregulated proteins included talin-1, fibrinogens, and adiponectin. Correlation analysis linked these changes to improvements in lipid profiles, vascular function, and circulating inflammatory markers. Pathway analysis revealed inhibition of lipid-regulatory pathways alongside enrichment of immune, metabolic, and vascular pathways, including lipoprotein metabolism and endothelial signaling. Bariatric surgery-induced cardiometabolic improvements were accompanied by adiposome proteomic remodeling, characterized by reduced inflammation and metabolic reprogramming. Full article

Oxidative stress (OS) significantly impairs poultry production; however, the protective mechanisms of rutin in the chicken liver remain unclear. In this study, we investigated the regulatory effects of rutin on oxidative stress and lipid metabolism using H₂O₂-exposed primary hepatocytes derived from chicken embryos. Specifically, we focused on antioxidant indicators, the Nrf2/Keap1 signaling pathway, and the ZAKα-mediated ribotoxic stress response (RSR). Results showed that pretreatment with 800 μmol/L rutin significantly alleviated oxidative damage by increasing superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, while decreasing malondialdehyde (MDA) and reactive oxygen species (ROS) levels. This protective effect was mediated by activation of the Nrf2/Keap1 signaling pathway and its downstream effectors, HO-1 and SOD2. Concurrently, rutin suppressed lipid accumulation, as evidenced by reduced levels of triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C), along with the downregulation of SREBP1 expression. Mechanistically, we found that rutin inhibited ZAKα and its downstream signaling, the p38/JNK pathway, which is associated with RSR. Crucially, co-treatment with ZAKα overexpression significantly attenuated the protective effects of rutin on both antioxidant defense and lipid regulation, confirming that rutin functions by inhibiting ZAKα-mediated signaling to restore Nrf2 activity. Molecular docking revealed a binding energy of −8.6 kcal/mol between rutin and ZAKα, verifying that ZAKα serves as a potential target for rutin. Collectively, these findings elucidate a novel mechanism whereby rutin enhances antioxidant defense and inhibits lipid deposition via the ZAKα-p38/JNK-Nrf2 signaling pathway, providing a theoretical basis for the application of rutin as a targeted regulator in poultry health. Full article

Atherosclerosis is a chronic inflammatory arterial disease and the primary underlying cause of cardiovascular morbidity and mortality worldwide. Its development and progression are driven by a mechanistically interconnected triad of endothelial dysfunction, oxidative stress, and vascular inflammation. Current pharmacotherapy, primarily focused on low-density lipoprotein cholesterol (LDL-C) reduction through statin-based and adjunctive therapies, does not fully address the residual inflammatory and calcific components of atherosclerotic risk. Menaquinone-7 (MK-7), a long-chain isoform of vitamin K2 with superior bioavailability and extrahepatic tissue distribution, has emerged as a multi-target modulator of atherogenic processes. Its classical function is to serve as a cofactor for the gamma-carboxylation of vitamin K-dependent proteins (VKDPs), principally matrix Gla protein (MGP), the primary endogenous inhibitor of vascular calcification. Beyond this established pathway, a growing body of experimental evidence indicates that MK-7 may modulate endothelial nitric oxide (NO) production through carboxylation-dependent activation of Growth Arrest-Specific Protein 6 (Gas6) and suppress lipid peroxidation and ferroptosis via Ferroptosis Suppressor Protein 1 (FSP1)-mediated reduction of vitamin K hydroquinone (VKH₂). In addition, it may attenuate nuclear factor kappa-B (NF-κB)-driven inflammatory gene transcription in vascular cells. Previous reviews mainly focused on how vitamin K2 influences vascular calcification and cardiovascular outcomes. However, emerging mechanistic evidence linking MK-7 to endothelial dysfunction, oxidative stress, ferroptosis, and vascular inflammation has not been comprehensively integrated. This review summarizes the current knowledge of in vitro, animal, observational, and randomized controlled trial evidence for MK-7 in the context of atherosclerosis. It particularly emphasises mechanistic pathways, the strength of evidence, and translational limitations, highlighting the lack of direct human vascular evidence in several areas. Full article

Citrus flavonoid intake is associated with beneficial effects on endothelial function. Our previous randomized control trial demonstrated that the concentration of Hesperetin-7-O-glucuronide (H7G) was positively correlated with the improvement in endothelial function in overweight and obese participants following blood orange juice consumption. To explore the underlying mechanism by which H7G improves endothelial function, we investigated the regulation of H7G on endothelial function in a permanent human endothelial cell line (EA. hy926 cells) under normal and oxidative conditions treated with high-oxidation low-density lipoprotein. The results indicated that H7G improved the expression of nitric oxide synthase 3 (NOS3), heme oxygenase 1 (HMOX1) ad glutamate cysteine ligase catalytic (GCLC), and inhibited the expression of endothelin-1 (EDN1), through the upregulation of miR-660-5p and inhibition of miR-21-5p. In summary, H7G improves endothelial cell function via the upregulation of miR-660-5p and the inhibition of miR-21-5p. Full article

Intensive aquaculture of rice field eel (Monopterus albus) is constrained by oxidative stress induced by high-density culture resulting in growth inhibition, while prophylactic antibiotics pose escalating risks of drug resistance and food safety hazards. This study addresses the critical need for developing efficient, environmentally friendly functional feed additives as sustainable growth promoters in intensive aquaculture. To investigate the dietary berberine (BBR) effect on promoting growth performance, hepatic antioxidant capacity and metabolism in M. albus, four experimental groups were established: control (CON, 0 mg/kg) and berberine-supplemented groups (BBR25, 25 mg/kg; BBR50, 50 mg/kg; BBR100, 100 mg/kg). Growth performance, serum biochemical parameters, hepatic antioxidant capacity, and liver metabolomics (LC-MS) were evaluated after the 8-week feeding trial. BBR50 and BBR100 had significantly increased final weight, weight gain rate (WG), and survival rate (SR), while reducing feed conversion ratio (FCR) (p < 0.05). Serum glucose (Glc), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased (p < 0.05), while high-density lipoprotein cholesterol (HDL-C) and phosphofructokinase (PFK) activity were increased (p < 0.05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly reduced (p < 0.05). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were upregulated (p < 0.05), whereas malondialdehyde (MDA) was downregulated (p < 0.05). Metabolomics identified 98 differential metabolites, with significant enrichment of metabolites associated with arachidonic acid metabolism, histidine metabolism, arginine/proline metabolism, tryptophan metabolism, and pathways related to mTOR signaling. Overall, dietary supplementation with 50 mg/kg BBR emerged as a practically favorable dose among the tested concentrations for promoting growth performance and feed utilization efficiency, whereas 100 mg/kg BBR was associated with lipid and amino acid metabolic alterations suggestive of metabolic reprogramming and antioxidant-related shifts, without conferring additional growth benefits. Full article

Neural tube defects (NTD) are congenital malformations that lead to structural abnormalities of the brain or spine. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1 KO), the main receptor for high-density lipoproteins, exhibit a high incidence of anterior NTD, which is associated with vitamin E deficiency and elevated levels of reactive oxygen species (ROS). Maternal supplementation with vitamin E, a micronutrient with antioxidant properties, completely prevents the occurrence of NTD and normalizes ROS levels in SR-B1 KO embryos, suggesting a contribution of oxidative stress to NTD in this model. In this work, we showed that SR-B1 KO embryos at gestational day E9.5 display higher levels of lipoperoxidative damage markers. Analysis of data obtained through shotgun lipidomics evidenced a selective and coordinated reorganization of fatty acid distribution, characterized by altered polyunsaturated and monounsaturated composition, together with reduced phosphatidylcholine and increased lysophosphatidylcholine levels, and diversion of fatty acids into triacylglyceride storage. Transcriptomic analysis revealed a coordinated upregulation of genes involved in phospholipid synthesis and remodeling, consistent with the altered lipid homeostasis observed in SR-B1 KO embryos. Together, these results provide novel information showing a potential link between oxidative stress and disruptions in mammalian embryonic lipid metabolism, highlighting phospholipid remodeling as a potential determinant of susceptibility to NTD. Full article

Previous studies have demonstrated that phloretic acid (PA), a phenolic compound, exerts beneficial effects on inflammation, oxidative stress, and aging. However, its effects on obesity and associated metabolic abnormalities, including dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD), remain unclear. To evaluate the effects of PA on these obesity-related metabolic alterations and explore the underlying mechanisms, male C57BL/6J mice were divided into three groups and fed for 10 weeks with a low-fat diet (10 kcal% fat), a high-fat diet (HFD, 60 kcal% fat), or an HFD containing 0.02% (w/w) PA. PA-supplemented mice showed no significant weight loss and fat loss. However, PA supplementation significantly reduced circulating levels of free fatty acid, triglyceride, and non-high-density lipoprotein cholesterol (HDL-C) while increasing HDL-C levels in HFD-fed mice. It also reduced hepatic lipid deposition and alleviated hepatocellular injury. These effects were accompanied by the coordinated modulation of hepatic lipid metabolism, including reduced lipogenesis and cholesterol esterification, enhanced fatty acid oxidation, and increased bile acid synthesis and excretion. Furthermore, PA attenuated hepatic oxidative stress and suppressed systemic and hepatic inflammation. These observations suggest that PA may counteract HFD-induced MASLD by modulating hepatic lipid metabolism, and that its anti-inflammatory and antioxidant effects may also contribute to these metabolic improvements. Full article