Search Results (670)

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders. Full article

There are currently no approved therapeutic treatments targeting metabolic dysfunction-associated steatotic liver disease (MASLD). Albumin, a liver-produced plasma protein with anti-inflammatory and antioxidant properties, is reduced in advanced liver disease. Considering the role of chronic obesity-induced inflammation in MASLD pathogenesis, we investigated whether albumin administration could prevent disease progression to metabolic dysfunction-associated steatohepatitis (MASH). MASLD was induced in mice using a high-fat and high-cholesterol (PC) treatment for 8 weeks, followed by treatment with bovine serum albumin (BSA; 0.8 mg/kg) every three days for another 8 weeks. This regimen prevented time-dependent weight gain, regardless of diet, with 57% and 27% reductions in mice fed a standard chow (Std Chow) or PC diet, respectively. Further, supplementation reduced nuclear factor kappa B (NF-κB) activation by 2.8-fold (p = 0.0328) in PC-fed mice, consistent with albumin’s known anti-inflammatory properties. Unexpectedly, albumin also reduced hepatic neutral lipid accumulation and circulating non-esterified fatty acids. While PC-fed mice did not exhibit full progression to MASH, albumin treatment significantly increased hepatic matrix metalloproteinase-2 expression, suggesting the inhibition of early fibrotic signalling. While further studies are needed to elucidate the underlying mechanisms, these findings offer new insight into the potential of albumin, either alone or in combination with other therapies, to reduce hepatic steatosis in MASLD. Full article

Background: Metabolic syndrome (MetS) is characterized by chronic inflammation, oxidative stress, and mitochondrial dysfunction. MetS is associated with increased intestinal permeability and dysbiosis. The objective of this study was to investigate the effects of peanut shell extract (PSE) and luteolin (LUT) on the kidneys, colon, and ileum in a MetS-like murine model. Methods: Thirty-six male Slc6a14^y/− mice were divided into four groups: low-fat diet (LFD), high-fat diet (HFD), HFD + 200 mg PSE/kg BW (PSE, p.o.), and HFD + 100 mg LUT/kg BW (LUT, p.o.) for 4 months. Outcome measures included glucose homeostasis, intestinal permeability, gut microbiome composition, and mRNA gene expression of mitochondrial homeostasis and inflammation/oxidative stress in the kidneys, colon, and ileum. Results: HFD resulted in glucose dysregulation with hyperglycemia and insulin resistance. PSE and LUT improved insulin tolerance and beta-cell function. PSE and LUT mitigated HFD-increased serum lipopolysaccharide-binding protein concentration. Perturbations in the gut microbiome were associated with HFD, and PSE or LUT reversed some of these changes. Specifically, Phocaeicola vulgatus was depleted by HFD and reverted by PSE or LUT. Relative to the LFD group, the HFD group (1) upregulated mitochondrial fusion (MFN1, MFN2, OPA1), mitophagy (TLR4, PINK1, LC3B), and inflammation (NFκB, TNFα, IL6), and (2) downregulated mitochondrial fission (FIS1, DRP1), biosynthesis (PGC1α, NRF1, NRF2, TFAM), electron transport chain (complex I), and antioxidant enzyme (SOD1) in the kidneys, colon, and ileum. Conclusions: PSE and LUT reversed such HFD-induced changes in the aforementioned gene expression levels. Full article

Background/Objectives: Metabolic syndrome (MetS) in adolescence increases chronic disease risk in adulthood. No study has explored the combined effects of skeletal muscle strength and dietary patterns in MetS. This study aimed to examine the individual and combined effects of dietary patterns and HGS on MetS and its components in Korean adolescents. Methods: Using the 2014–2019 Korea National Health and Nutrition Examination Survey data, a weighted sample of approximately 3.75 million adolescents was included. Dietary patterns were derived using principal component analysis. Relative handgrip strength (HGS) was calculated. Multivariable logistic regression and relative excess risk due to interaction (RERI) were used to assess dietary patterns, HGS, and MetS, stratified by sex and adjusted for age, smoking, alcohol consumption, economic status, residential area, and physical activity. Results: Low HGS was independently associated with a high odds of developing MetS in both men (OR, 1.108; 95% CI, 1.038–1.182) and women (OR, 1.128; 95% CI, 1.047–1.216). In contrast, dietary pattern alone was not significantly associated with MetS. Men with both low HGS and unhealthy dietary patterns (processed fat or Western diet) had higher odds of developing MetS, even though the interaction was sub-additive, as indicated by negative RERI values (processed fat: −0.22; Western diet: −0.11). Conclusions: Low HGS was a significant risk factor for MetS in Korean adolescents. Although no synergistic interaction was observed, low HGS remained a significant independent risk factor for MetS, underscoring the need to promote muscular strength in adolescents even in the absence of an unhealthy diet. Full article

Background/Objectives: The establishment of early gut microbiota is crucial for host health. Lactoferrin (LF), which is present in breast milk, positively impacts gut microbiota composition. However, the effect of lactation LF on the establishment and composition of early gut microbiota in different disease models in adulthood remains unclear. Methods: Lactation-LF-deficient mice were established using systemically LF–knocked-out maternal mice. This study assessed the maturity of the gut microbiota in LF feeding-deficient mice in relation to age and changes in the gut microbiota in adult high-fat diet (HFD)-induced obesity, dextran sodium sulfate (DSS)-induced acute colitis, and chronic unpredictable mild stress (CUMS)-induced depression models. Results: Compared to LF intake during lactation, LF deficiency during lactation increased the abundance of potentially pathogenic bacteria in the gut, resulting in abnormal microbial maturation. LF intake during lactation aggravated gut microbiota dysbiosis induced via HFD, DSS, and CUMS in adulthood and may change the function of Enterorhabdus, GCA-900066575, Peptococcus, Tuzzerella, Akkermansia, and Desulfovibrio. Comparing the different models revealed that bacteria that were jointly upregulated via HFD and DSS exhibited increased levels of inflammation and oxidation. LF deficiency during lactation may weaken the association between an HFD and inflammatory bowel disease (IBD). The changing trends in many gut microbes caused by DSS and HFD were opposite to those that changed with age. Conclusions: Lactoferrin deficiency increases the abundance of potential pathogens and disrupts microbial maturation. This lack of LF exacerbates dysbiosis in models of obesity, colitis, and depression. Regulating the gut microbiota according to the rules of microbial succession during the maturation process of gut microbiota may improve gut microbiota dysbiosis in patients with obesity and IBD. Full article

Background: Diabetic lung disease, characterized by inflammation and fibrosis, is an emerging chronic complication of type 2 diabetes mellitus (T2DM). However, systematic studies on the effects of exercise interventions remain limited. This study aimed to investigate the impact of different exercise types (swimming, resistance training, and high-intensity interval training [HIIT]) on pulmonary inflammation and fibrosis in T2DM mice, and to explore underlying molecular mechanisms. Methods: A T2DM mouse model was established by a high-fat diet (HFD) combined with streptozotocin (STZ) induction. Mice were randomly divided into sedentary control, swimming, resistance training, and HIIT groups, and underwent 8 weeks of exercise intervention. After the intervention, body composition was assessed. Lung histopathological changes were evaluated by hematoxylin&eosin (HE) and Masson staining. Inflammatory cytokines, fibrosis markers, and the expression of the TGF-β1/Smad signaling pathway were detected. Macrophage infiltration and polarization were also analyzed. Results: Exercise intervention improved body composition and reduced oxidative stress in T2DM mice. All three exercise modalities downregulated inflammatory cytokine expression, inhibited macrophage activation and M1 polarization, and promoted M2 polarization. Additionally, exercise improved lung tissue structure, reduced collagen deposition, and decreased the expression of fibrosis-related markers. Furthermore, anti-fibrotic effects were mediated by suppression of the TGF-β1/Smad signaling pathway and inhibition of epithelial-mesenchymal transition (EMT). Among the interventions, HIIT demonstrated the strongest inhibitory effect on the TGF-β1/Smad pathway, while swimming showed the most significant anti-inflammatory benefits. Conclusions: Different types of exercise effectively alleviate pulmonary inflammation and fibrosis in T2DM mice. These effects are closely related to the inhibition of oxidative stress, regulation of macrophage polarization, and suppression of TGF-β1/Smad signaling activation, with swimming and HIIT demonstrating superior protective benefits. Full article

Background: Diabetic cardiomyopathy (DCM) is characterized by progressive cardiac dysfunction, metabolic dysregulation, myocardial fibrosis, and mitochondrial impairment. Existing animal models, such as streptozotocin (STZ)-induced models, suffer from high mortality and fail to replicate chronic metabolic dysregulation induced by high-fat diets (HFD), whereas HFD or HFD/STZ-combined rodent models require high maintenance costs. This study aimed to establish a zebrafish HFD-DCM model to facilitate mechanistic exploration and drug discovery. Methods: Eighty wild-type female zebrafish were divided into normal diet (N, 6% fat) and HFD (H, 24% fat) groups and fed the diet for 8 weeks. Metabolic phenotypes were evaluated using intraperitoneal glucose tolerance tests and insulin level analysis. Cardiac function was assessed by using echocardiography (ejection fraction, E peak). Structural, metabolic, and oxidative stress alterations were analyzed by histopathology (H&E, Masson, and Oil Red O staining), molecular assays (RT-qPCR, Western blotting), and mitochondrial structure/function evaluations (respiratory chain activity, transmission electron microscopy, and DHE staining). Results: HFD-fed zebrafish developed obesity, insulin resistance, and impaired glucose tolerance. Echocardiography revealed cardiac hypertrophy, reduced ejection fraction, and diastolic dysfunction. Excessive lipid accumulation, upregulated fibrosis/inflammatory markers, impaired mitochondrial respiration, elevated reactive oxygen species levels, and a disrupted redox balance were observed. Conclusions: We established a female zebrafish HFD model that recapitulates human DCM features, including hypertrophy, metabolic dysregulation, fibrosis, inflammation, and mitochondrial dysfunction. This model offers novel insights into DCM pathogenesis and serves as a valuable platform for mechanistic studies and targeted drug screening. Full article

Background/Objectives: High-fat-diet (HFD) consumption drives chronic liver injury via gut dysbiosis and metabolic disturban. Apple cider vinegar, rich in polyphenols and organic acids, shows potential in metabolic regulation. This study aimed to investigate whether apple cider vinegar powder (ACVP) alleviates HFD-induced liver injury by modulating the gut–liver axis. Methods: For 12 weeks, C57BL/6 J mice received daily ACVP gavage while being fed a HFD. A series of biological assessments were conducted, including systemic metabolic evaluations (body weight, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and lipid/glucose levels), hepatic steatosis (hematoxylin and eosin (H&E) staining), intestinal microbiome characterization (16S rRNA gene genomic analysis), and comprehensive metabolite profiling of cecal contents (non-targeted metabolomics). Pearson correlation networks integrated multi-omics data. Results: ACVP attenuated HFD-induced weight gain by 26.3%, hepatomegaly and dyslipidemia, as well as reduced hepatic lipid vacuoles and serum ALT (48%)/AST (21.5%). ACVP restored gut microbiota diversity, enriching Muribaculaceae. Cecal metabolomics identified 38 HFD-perturbed metabolites reversed by ACVP, including indolelactate, hyocholate, and taurocholic acid. the Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed ACVP-mediated recovery of linoleic acid metabolism. Correlation networks linked Akkermansia to anti-inflammatory metabolites (e.g., trans-ferulic), while Desulfobacterota correlated with pro-inflammatory oxylipins (e.g., 12,13-dihydroxy-9Z-octadecenoic acid (DHOME)). Conclusions: ACVP mitigates HFD-induced liver injury by remodeling gut microbiota, restoring microbial metabolites, and enhancing gut–liver crosstalk. Full article

In recent years, plant-based fermented foods (PBFs) have become popular all over the world due to their high nutritional value. Compared with traditional foods, PBFs can effectively address dietary issues of high fat content, excessive calories, and elevated cholesterol levels in food formulations, while providing higher nutritional value and enhanced sensory properties (taste and flavor) than conventional plant-based products. These characteristics make PBFs more suitable for people’s yearning for a healthy diet. This review discussed the close relationship between PBFs and human health, elaborating on the definition of PBFs, common types, and the beneficial effects that occur during the fermentation process for human health. Furthermore, we also explored the nutritional value of PBFs. Herein, PBFs are not only rich in probiotics, organic acids, and various bioactive substances that promote gut health and boost immunity but also play a positive role in preventing certain chronic diseases. Finally, this article looks forward to the future development trends of PBFs, predicting their significant potential in healthy eating and sustainability. Full article

Depression and obesity are comorbid conditions linked through shared neuroinflammatory and immune mechanisms. This study examined the effects of chronic cannabidiol (CBD) treatment on behavior and neuroinflammatory gene expression in female rats exposed to a combined model of high-fat diet (HFD) and unpredictable chronic mild stress (UCMS). Rats were subjected to an acute HFD for 2 weeks, followed by 4 weeks of UCMS. CBD (10 mg/kg, i.p.) or vehicle was administered during the final 2 weeks of UCMS. Specifically, mRNA levels of nuclear factor kappa B1 (NF-κB1), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were measured in the ventromedial prefrontal cortex (vmPFC) and CA1. CBD’s effects varied depending on the type of stressor. It promoted coping behavior, increased locomotion, reduced freezing, and restored UCMS-induced depressive-like behavior in a splash test. In the vmPFC, CBD normalized the HFD- and UCMS-induced increase in il1β, and downregulated nfkb1 and tnfa expression. In the CA1, it normalized stress-induced downregulation in nfkb1 expression. These findings suggest that the efficacy of CBD in modulating both behavior and neuroinflammation is contingent upon the nature of the stress exposure, highlighting its potential as a targeted treatment for stress-related neuropsychiatric disorders in females. Full article

Background: The Mediterranean diet is considered one of the healthiest and safest diets for preventing chronic diseases. The primary objective of this study was to assess the association between adherence to the Mediterranean diet and the occurrence of prediabetes in a representative population of Bialystok, Poland. Prediabetes is a condition characterized by elevated blood glucose levels that are higher than normal but not yet in the diabetic range, indicating an increased risk of developing type 2 diabetes. Methods: The study participants were selected into healthy control (HC) and prediabetic (PreD) groups based on age and gender. Biochemical measurements included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting glucose (FG), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6). Additionally, blood pressure, handgrip strength, anthropometric parameters, and body composition were measured. Information on patients’ social data, medical history, and lifestyle history was collected using questionnaires developed for this study. A standardized questionnaire, the Satisfaction with Life Scale (SWLS), was used to assess life satisfaction. Dietary total antioxidant capacity (DTAC) and dietary total polyphenol intake (DTPI) were determined using a 3-day nutritional interview and appropriate databases containing information on polyphenols and the antioxidant potential of food products. To assess adherence to the Mediterranean diet recommendations, a 9-item Mediterranean Diet Index (MDI) was used. Results: It was found that the mean MDI for the entire group was low (3.98 ± 1.74), and the HC was characterized by a significantly higher MDI compared to the PreD. A statistically significant positive correlation was found between MDI and HDL-C, whereas a negative correlation was found between MDI and FG, homeostatic model assessment for insulin resistance (HOMA-IR), diastolic blood pressure (DBP), IL-6, body mass index (BMI), waist-hip ratio (WHR), waist circumference, visceral fat mass, android/gynoid fat ratio. Conclusions: Abdominal obesity was shown to significantly reduce life satisfaction. In model 3, after adjusting for age, sex, dietary energy intake, alcohol consumption, and smoking, each additional MDI point indicated a 10% lower risk of prediabetes. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver condition linked to obesity and metabolic imbalance. Alterations in the gut microbiota are increasingly recognized as contributors to its progression. Alistipes putredinis, a core member of the human gut microbiota, has been linked with metabolic health, but its functional role in MASLD remains unclear. Methods: This study evaluated the potential of A. putredinis strain Ap77, isolated from the stool of a healthy adult, to mitigate MASLD-related alterations in a high-fat diet (HFD)-induced rat model. Animals were divided into normal chow (NC), HFD, and HFD plus Ap77 groups and received daily oral gavage of Ap77 or PBS for 8 weeks. Results: Ap77 supplementation attenuated the body weight increase associated with high-fat diet consumption. It also reduced hepatic triglyceride levels and fat mass and improved liver histology. Transcriptomic analysis revealed suppression of inflammation-associated pathways. Correspondingly, the concentrations of IL-1β, IL-6, and TNF-α in both the liver and serum were reduced. Ap77 supplementation was associated with an increased abundance of health-associated bacterial genera, such as Lachnospiraceae UCG_010, Akkermansia, and Flavonifractor, as well as elevated serum levels of butyrate, indole-3-propionic acid, and indoleacrylic acid. Notably, correlation analysis revealed that Lachnospiraceae UCG_010 was positively associated with these metabolites. Conclusions: A. putredinis Ap77 alleviates hepatic steatosis and inflammation in MASLD, potentially by reshaping gut microbiota and suppressing inflammation-related signaling pathways. Full article

Background: An unbalanced dietary intake of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been associated with chronic inflammation and oxidative stress, both of which contribute to the pathophysiology of obesity. Objective: We aimed to evaluate the effects of a diet with an n-6:n-3 PUFA ratio of 5:1 on body composition, biochemical parameters, and the gene expression of cytokines and antioxidant enzymes in a murine model of diet-induced obesity. Methods: A diet-induced obesity model was established in C57BL6/J mice over 17 weeks. Mice were then fed different diets for 8 weeks: a control diet (chow), a high-fat diet with a 30:1 n-6:n-3 ratio (HFD-30:1), and a high-fat diet enriched with n-3 fatty acids, with a 5:1 n-6:n-3 ratio (HFD-5:1). Body weight and food intake were monitored throughout this study. Biochemical parameters were measured, and the expression of antioxidant enzymes and cytokine genes was analyzed by qPCR. Data were analyzed using GraphPad Prism software. Results: The HFD-5:1 group exhibited a significant reduction in body weight (p = 0.0182), liver tissue weight (p = 0.01), serum glucose levels (p = 0.010), area under the curve (AUC) (p = 0.0161), cholesterol (p < 0.0001), and triglycerides (p = 0.0069) compared to the HFD-30:1 group. The body weight in the HFD-5:1 group decreased to levels comparable to the control group. Additionally, the expression of the inflammatory cytokine genes Ccl2 (p = 0.0389) and Tgfb1 (p = 0.0226) was significantly reduced. Conclusions: These findings suggest that adjusting the dietary n-6:n-3 ratio to 5:1 modulates inflammation-related gene expression and improves metabolic markers in obese mice, supporting its potential relevance for future translational research. Full article

Obesity is a major risk factor for atrial fibrillation (AF), the most common serious cardiac arrhythmia, but the molecular mechanisms underlying obesity-induced AF remain unclear. In this study, we subjected mice to a chronic high-fat diet and acute sympathetic activation to investigate how obesity promotes AF. Surface electrocardiography revealed that obesity and sympathetic activation synergize during intracardiac tachypacing to induce AF. At the cellular level, this combination facilitated delayed afterdepolarizations in atrial myocytes, implicating altered Ca²⁺ dynamics. Interestingly, obesity did not affect the expression of key atrial Ca²⁺-handling proteins, including the cardiac sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a). However, obesity increases the proportion of inhibitory phospholamban (PLN) monomers and decreases PLN phosphorylation, suggesting reduced SERCA2a activity. Paradoxically, Ca²⁺ reuptake in atrial myocytes from obese mice was similar to that achieved by potent small-molecule SERCA2a activators. We found that adrenergic stimulation increased Ca²⁺ transient amplitude without altering Ca²⁺ reuptake in myocytes from obese mice. Transcriptomic analysis revealed that a high-fat diet upregulated neuronatin, a protein involved in obesity that enhances SERCA2-mediated Ca²⁺ reuptake in neurons. We propose that obesity enables SERCA2a activation independently of PLN regulation, while adrenergic stimulation triggers arrhythmogenic Ca²⁺-induced Ca²⁺ release, promoting AF. In conclusion, this study demonstrates that obesity causes a paradoxical dysregulation of SERCA2a in atrial myocytes, with increased activity despite higher levels of inhibitory PLN monomers and reduced PLN phosphorylation. These findings offer new insights into the cellular mechanisms of obesity-induced AF and suggest potential therapeutic targets. Full article