Search Results (225)

Background: Long pulse width stimulation (LPWS; 120–150 ms) has the potential to stimulate denervated muscles in persons with spinal cord injury (SCI). We examined whether testosterone treatment (TT) + LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in SCI persons with denervation. We hypothesized that one year of combined TT + LPWS would downregulate gene expression of muscle atrophy and upregulate gene expression of muscle hypertrophy and increase mitochondrial health in SCI persons with lower motor neuron (LMN) injury. Methods: Ten SCI participants with chronic LMN injury were randomized into either 12 months, twice weekly, of TT + LPWS (n = 5) or a TT+ standard neuromuscular electrical stimulation (NMES; n = 5). Measurements were conducted at baseline (week 0), 6 months following training (post-intervention 1), and one week following 12 months of training (post-intervention 2). Measurements included body composition assessment using magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA). Metabolic profile assessment encompassed measurements of resting metabolic rate, carbohydrate and lipid profiles. Finally, muscle biopsy was captured to measure RNA signaling pathways and mitochondrial oxidative phosphorylation. Results: Compliance and adherence were greater in the TT + NMES compared to the TT + LPWS group. There was a 25% increase in the RF muscle CSA following P1 measurement in the TT + LPWS group. There was a recognizable non-significant decrease in intramuscular fat in both groups. There was a trend (p = 0.07) of decrease in trunk fat mass following TT + LPWS, with an interaction (p = 0.037) in android lean mass between groups. There was a trend (p = 0.08) in mean differences in DXA-visceral adipose tissue (VAT) between groups at P1 measurements. For genes targeting muscle atrophy, TT + LPWS showed a trending decline in MURF1 and FOXO3 genes returning to similar levels as TT + NMES before 12 months. Conclusions: These pilot data demonstrated the safety of applying LPWS in persons with SCI. Six months of TT + LPWS demonstrated increases in rectus femoris muscle CSA. The effects on muscle size were modest between groups. Signaling pathway analysis suggested downregulation of genes involved in muscle atrophy pathways. Future clinical trials may consider a home-based approach with more frequent applications of LPWS. Full article

Background/Objectives: The increase in the global prevalence of obesity has created a need for safe and effective preventive strategies. Probiotics have gained attention for their potential to modulate the gut microbiota and improve metabolic health. In this study, we examined the anti-obesity effects of Lactiplantibacillus plantarum strain 06CC2 (LP06CC2) in a mouse model of mild diet-induced obesity that mimics early-stage metabolic imbalance without significant body weight gain. Methods: Mice were fed a high-fat diet for 8 weeks, with or without LP06CC2 supplementation. Biochemical assays were used to determine the metabolic effects of LP06CC2, and 16S rRNA sequencing was performed to analyze the gut microbiota. Results: LP06CC2 attenuated epididymal fat accumulation and adipocyte hypertrophy, improved the gene expression profiles related to lipid metabolism and inflammation in adipose tissue, and reduced early hepatic steatosis. 16S rRNA sequencing revealed that LP06CC2 modulated the diversity and composition of the gut microbiota, notably suppressing HFD-induced increases in Mucispirillum schaedleri and other taxa associated with inflammation. LP06CC2-treated mice exhibited higher alpha diversity and partial restoration of their microbial profiles toward those of the normal diet-fed animals. LP06CC2 also downregulated pro-inflammatory cytokines and genes related to lipid uptake while modulating markers of thermogenesis and lipolysis. Conclusions: These findings indicate that LP06CC2 can prevent fat accumulation and gut dysbiosis in the pre-obese state, supporting its potential as a functional food ingredient for early intervention in obesity. Further human trials and studies using advanced obesity models are warranted to confirm its efficacy and elucidate its underlying mechanisms of action. Full article

Background/Objectives: Obesity is a major risk factor for cardiovascular disease (CVD), but traditional risk calculators such as Systematic COronary Risk Evaluation (SCORE2) may not fully capture the elevated risks in individuals with obesity, especially when metabolic health is considered. This study aimed to evaluate the effectiveness of QRESEARCH risk estimator version 3 (QRISK3) in estimating 10-year cardiovascular risk in individuals with varying obesity phenotypes compared to SCORE2. Methods: A total of 88 participants (25 men, 63 women; mean age 37.4 ± 11.8 years) were categorized into four obesity phenotypes according to metabolic and anthropometric criteria. The 10-year CVD risk was calculated using SCORE2 and QRISK3 algorithms. Functional cardiovascular assessment included blood pressure (BP) measurement and electrocardiogram (ECG) interpretation for conduction abnormalities and left ventricular hypertrophy (LVH). Biochemical analysis included carbohydrate metabolism (fasting glucose, postprandial glucose, HbA1c) and lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides, atherogenic index). Results: SCORE2 underestimated CVD risk (3–8%), whereas QRISK3 predicted higher values (6–16%), particularly in metabolically unhealthy phenotypes. LVH occurred in 26–45% of participants, with elevated BP and early subclinical ECG changes even in metabolically healthy obesity individuals. Carbohydrate metabolism disturbances were observed in metabolically unhealthy participants with normal or elevated BMI, while lipid abnormalities—including elevated total cholesterol, LDL-C, triglycerides, and atherogenic index—were prominent in these metabolically unhealthy phenotypes. Insulin resistance, assessed via the triglyceride–glucose index, exceeded reference ranges in all obesity phenotypes, with the highest values seen in metabolically unhealthy individuals. Conclusions: QRISK3 provides a more precise and thorough assessment of 10-year cardiovascular risk in individuals with obesity than SCORE2. These findings highlight the importance of incorporating anthropometric and metabolic data into cardiovascular risk assessments and support the clinical use of QRISK3 for more personalized risk stratification, especially in populations with obesity and metabolic disturbances. Early identification of high-risk individuals using QRISK3 could lead to more timely and targeted preventive interventions, improving long-term cardiovascular outcomes. Full article

Cassava fiber (CF) is a novel dietary fiber extracted from cassava by-products. To investigate its anti-obesity mechanism, obesity was induced in mice through a high-fat diet (HFD). Dietary supplementation with 10% CF significantly reduced body weight, body fat, triglycerides, low-density lipoprotein cholesterol, total cholesterol, and fasting blood glucose in mice. CF effectively ameliorated hepatic steatosis and adipocyte hypertrophy, increased the villus height-to-crypt depth ratio, enhanced mucus secretion by intestinal goblet cells, down-regulated the expression of ileal lipid absorption-related genes (NPC1L1, CD36, and FABP2), and up-regulated the short-chain fatty acid receptor GPR43, collectively improving intestinal health. Compared to HFD mice, CF altered the gut microbiota: it increased beneficial Actinobacteria (including Bifidobacterium and Blautia) and decreased Proteobacteria (including Desulfovibrio) (p < 0.05). Functional analysis showed that the HFD mice microbiota was enriched in genes linked to disease (e.g., lipid metabolism disorders, cancer, antibiotic resistance), whereas CF-enriched microbiota had genes for energy, carbohydrate, and pyruvate metabolism. Compared to microcrystalline cellulose, CF and MCC both alleviated HFD-induced obesity. In summary, cassava fiber helped prevent obesity in mice by modulating gut microbes, strengthening the gut barrier, and improving host metabolic balance. Full article

Background/Objectives: Increased fat intake and high content of saturated fatty acids in the diet are associated with higher body weight and an increased risk of obesity. This study aimed to determine the impact of a high-fat diet (HFD) on white adipose tissue (WAT) metabolism and to verify whether this effect depends on the sources of lipids in HFD. Methods: Male C57BL/6J mice, 7 weeks old, received a control (Ctrl.) or high-fat diet (HFD) with 10% and 45% energy from fat, respectively, for 15 weeks. Lard was used as the main dietary fat in the HFD group. Next, the HFD group was subdivided into HFD-L, HFD-CO, HFD-OO and HFD-FO groups differing in the lipid sources (lard, coconut oil, olive oil, fish oil, respectively). The experiment was continued for 12 consecutive weeks. The study analyzed the concentration of different fatty acids in visceral (VAT) and subcutaneous (ScAT) adipose tissue; the levels of autophagy markers: beclin1, Atg5, LC3, p62, AMPK; ER stress markers: phos-PERK, CHOP, XBP-1 and oxidative stress parameters: TAS and TBARS in VAT and ScAT. Results: Mice in all HFD groups showed increased body mass and adipose tissue hypertrophy. Blood glucose concentration remained elevated in the HFD-L group but normalized in other HFD groups by the end of the dietary intervention. Fatty acid content in VAT and ScAT reflected the dietary sources in HFD. The HFD-L, HFD-CO, HFD-OO groups showed increased beclin1, ATG5, and p62 levels in VAT but the LC3-II/LC3-I ratio was similar to the control, suggesting impaired autophagic flux. In the HFD-FO group, the LC-II/LC-I ratio was elevated, along with decreased p62 levels, indicating active autophagic degradation. Changes in autophagy activity were insignificant in ScAT. ER stress markers were also mostly unaffected by HFD in both adipose tissue depots. TAS and TBARS values in VAT and ScAT were similar in the HFD-L and HFD-CO groups, and the HFD-OO group showed increased TAS and decreased TBARS, while the HFD-FO reduced TBARS. Conclusions: Antioxidant capacity and autophagy activity in WAT depended on fat content and lipid source, especially in the visceral depot. Fish oil induced changes in cellular metabolism, especially in VAT, diminishing the detrimental effects of HFD. Full article

Background: Bee pollen is a uniquely complete nutritional product that has shown promise in alleviating obesity. While existing research has largely focused on the role of gut microbiota in obesity, the mechanisms by which bee pollen influences bile acid (BA) metabolism via microbial regulation remain poorly understood. Methods: This study hypothesized that Schisandra chinensis bee pollen extract (SCPE) could mitigate high-fat diet (HFD)-induced obesity by regulating BA metabolism. Results: In a 12-week animal experiment, SCPE supplementation significantly reduced body weight gain, lipid accumulation, and adipocyte hypertrophy, while improving insulin sensitivity and relieving hepatic oxidative stress. These benefits were attributed to an increased relative abundance of bile salt hydrolase (BSH)-producing microbes, including Bacteroides, Lachnospiraceae NK4A136 group, and Akkermansia, which modulated BA metabolism by improving the expression of BA metabolism-related genes and reducing the concentrations of various types of BAs. Conclusions: These findings provide new insights into the mechanism by which SCPE alleviates obesity through the gut microbiota-BA axis and support the potential of bee pollen as a functional food for obesity management. Full article

The global rise in obesity and metabolic disorders has intensified the demand for safe and effective sugar alternatives. Monellin, a naturally sweet protein derived from Dioscoreophyllum cumminsii, serves as an excellent sugar alternative, but its broader application has been constrained by poor thermal stability and limited evaluation of long-term metabolic effects. In this study, we evaluated the metabolic effects of MNEI-Mut6, a boiling-resistant single-chain monellin variant, in male C57BL/6 mice fed standard chow supplemented with either 4% sucrose or an equivalent sweetness concentration of MNEI-Mut6 for 16 weeks. Compared with sucrose, MNEI-Mut6 did not promote weight gain, preserved insulin sensitivity, and maintained glucose homeostasis. In addition, MNEI-Mut6 reduced hepatic lipid accumulation and adipocyte hypertrophy without inducing hepatotoxic or nephrotoxic effects. Collectively, these findings demonstrate that MNEI-Mut6, a thermally stable and metabolically neutral sweetener, is a promising and safer alternative to sucrose and artificial sweeteners suitable for application in food processing and product formulation. Full article

Diabetic nephropathy (DNR) remains a major complication of type 2 diabetes with limited options to halt progression. We evaluated whether DNR (a sulfur-rich extract from Hongsan garlic) confers renoprotection in a db/db mouse model. Seventy male C57BLKS/J mice were randomized into seven groups (db/m control, db/db control, metformin 250 mg/kg, DNR 100/300/900 mg/kg, and metformin 250 mg/kg + DNR 300 mg/kg) and treated orally for eight weeks. Physiological, biochemical, urinary, histological, and immunohistochemical(IHC) endpoints were assessed, including serum creatinine, blood urea nitrogen(BUN), lipids, glucose, urinary microalbumin/albumin-to-creatinine ratio(ACR), glomerular area, mesangial expansion, and renal KIM-1 and TGF-β1 expression. Chemical profiling of the DNR extract by HPLC and LC–MS/MS identified allicin as a principal sulfur-containing constituent, exhibiting a distinct retention peak at 2.90 min and a protonated molecular ion at m/z 162.1 [M]⁺ with diagnostic fragment ions at m/z 145.1, 120.1, and 99.0. Allicin was qualitatively confirmed as a characteristic component of DNR, serving as a representative chemical marker for compositional characterization. DNR produced dose-dependent improvements: reductions in serum creatinine and BUN, improved lipid and glycemic profiles, decreased urinary microalbumin and ACR, and amelioration of glomerular hypertrophy and mesangial matrix expansion. IHC showed lower KIM-1 and TGF-β1 staining in treated groups. Effects at higher DNR doses were comparable to or additive with metformin for several endpoints. These findings indicate that DNR has promising renoprotective effects in this preclinical model. Full article

Left ventricular hypertrophy (LVH) refers to the pathological thickening of the myocardial wall and is strongly associated with several adverse cardiac outcomes and sudden cardiac death. While the biomechanical drivers of LVH are well established, growing evidence points to a critical role for cardiac and systemic metabolism in modulating hypertrophic remodeling and disease pathogenesis. Despite the efficiency of fatty acid oxidation (FAO), LVH hearts preferentially increase glucose uptake and catabolism to drive glycolysis and oxidative phosphorylation (OXPHOS). The development of therapies to increase and enhance LFCA FAO is underway, with promising results. However, the mechanisms of systemic metabolic states and LCFA dynamics in the context of cardiac hypertrophy remain incompletely understood. Further, it is unknown to what extent cardiac metabolism is influenced by whole-body energy balance and lipid profiles, despite the common occurrence of lipotoxicity in LVH. In this study, we measured whole-body and cellular respiration along with analysis of lipid and glycogen stores in a mouse model of LVH. We found that loss of the cardiac-specific gene, myosin-binding protein C3 (Mybpc3), resulted in depletion of adipose tissue, decreased mitochondrial function in skeletal muscle, increased lipid accumulation in both the heart and liver, and loss of whole-body metabolic flux. We found that supplementation of exogenous LCFAs boosted LVH mitochondrial function and reversed cardiac lipid accumulation but did not fully reverse the hypertrophied heart nor systemic metabolic phenotypes. This study indicates that the LVH phenotype caused systemic metabolic rewiring in Mybpc3^−/− mice and that exogenous LCFA supplementation boosted mitochondrial function in both cardiac and skeletal muscle. Full article

Obesity contributes to the development of metabolic disorders such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) through sustained low-grade inflammation and mitochondrial dysfunction. In obesity, hypertrophied adipose tissue release high levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and elevates circulating free fatty acids. These changes promote systemic insulin resistance and ectopic lipid deposition. Mitochondrial dysfunction, including reduced oxidative phosphorylation, excess reactive oxygen species (ROS) production, and mitochondrial DNA damage, further stimulate inflammatory pathways such as the NLRP3 inflammasome, creating a feedback loop that worsens metabolic stress. Ultimately, this interaction disrupts energy balance, weakens insulin signaling, and accelerates β-cell dysfunction and hepatic steatosis. In both T2DM and MASLD, oxidative stress, defective mitochondrial quality control, and dysregulated immunometabolic responses are consistently observed pathophysiological features. Interventions aimed at reducing inflammation and restoring mitochondrial function—including lifestyle modification, mitochondria-targeted therapies, inflammasome regulation, and enhancement of mitochondrial biogenesis or mitophagy—may retard disease progression. Full article

Diabetic nephropathy (DN) is a consequence of diabetes mellitus (DM), in which hyperglycemia triggers osmotic and oxidative stress and activates inflammatory pathways. These processes damage kidney cells, with mesangial cells (MCs) undergoing mesangial expansion. Antihyperglycemic drugs prevent the progression of renal disease. Although tamsulosin is not conventionally used for the treatment of DN, its previously reported anti-fibrotic and anti-inflammatory effects in liver and lung injury models suggest that it may exert renoprotective actions like those of pioglitazone, which has also been shown to improve cellular carbohydrate and lipid metabolism. MCs were exposed to 20 mM glucose medium and treated with either 50 nM tamsulosin or 100 nM pioglitazone. Subsequently, cell proliferation, inflammatory markers (NF-κB, IL-1β, IL-17), fibrogenic markers (TGF-β, collagen I), oxidative stress parameters (NRF2, superoxide), and indicators of mesangial activation (α-SMA, rhodamine–phalloidin) were assessed in vitro. Both treatments reduced cellular proliferation and hypertrophy, attenuated the release of reactive oxygen species (ROS), decreased IL-17 and α-SMA expression, and reduced mesangial activation and hypertrophy. In an in vivo model of DN in Wistar rats, both treatments decreased mesangial cell activation and expansion. In conclusion, tamsulosin and pioglitazone exert anti-fibrogenic and anti-inflammatory effects in MCs exposed to HG, thereby limiting mesangial activation and expansion. Full article

Background/Objectives: Recent studies suggest that plasma ceramide levels may be better predictors of CVD risk than LDL cholesterol. Ceramides are part of the sphingolipid class of lipids and are the central intermediates in complex sphingolipid biosynthesis. Sphingolipids are crucial for cellular structure and have important biological roles as complex signaling lipids, structurally and functionally differentiated by their acylated fatty acid. Higher plasma concentrations of 16:0 ceramide are associated with increased risk of heart failure. In contrast, higher concentrations of 22:0 plus 24:0 ceramide are associated with lower risk. We aim to address how alterations in these lipids can affect the human cardiac hypertrophic response. Methods: We silenced the ceramide synthase genes (CERS) responsible for the production of 16:0 ceramide (CERS5/6) or 22:0 and 24:0 ceramide (CERS2) in immortalized human ventricular cardiomyocytes and examined the altered cardiac hypertrophic response to phorbol 12-myristate 13-acetate treatment by examining changes in the transcriptome. Results: We discovered that silencing CERS2 or CERS5/6 drastically altered the cardiac cell hypertrophic response. We demonstrated that human cardiomyocytes with silenced CERS2 appeared to have an exacerbated hypertrophy response, while cardiomyocytes with silenced CERS5/6 had a more favorable response, suggesting that CERS2 and CERS5/CERS6 and their gene product metabolites may have opposing roles in the development and progression of CVD. Conclusions: The exact mechanisms through which various ceramides contribute to CVD progression are still unknown. This study will help elucidate the role of specific ceramides during cardiac hypertrophy and suggests that drugs targeting specific sphingolipids can potentially be a viable treatment option for the prevention of CVD. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses several cardiometabolic risk factors (obesity, insulin resistance, diabetes, and dyslipidemia), in addition to hepatic steatosis. Therefore, treatment is often challenging and frequently involves polypharmacy. This study investigated whether the combination of empagliflozin/metformin improves MASLD disease outcomes in an experimental model of metabolic syndrome (MS). To evaluate the efficacy of the empagliflozin/metformin (12.5/850 mg/kg/day/30 days) combination, male Wistar rats (200–220 g) were fed a Western-type diet and sugary drink to induce MS. Biochemical parameters, markers of liver damage, oxidative stress, and histopathological analysis were assessed. Also, the expression of transcription factors associated with carbohydrate and lipid metabolism and the modulation of oxidative stress were assessed. The analyses were performed with the combination and with the drugs independently. The combination empagliflozin/metformin decreased body weight, plasma triglycerides, and total cholesterol levels, while improving fasting blood glucose, oral glucose tolerance test, and plasma HDL-cholesterol levels. Additionally, it prevented hepatic hypertrophy, liver damage at both biochemical and histological levels, and intrahepatic lipid accumulation. The combination also demonstrated a significantly greater effect in improving mitochondrial function and reducing oxidative stress by modulating the Nrf2-mediated pathway. The empagliflozin/metformin combination therapy mitigates MASLD progression, likely by improving liver and mitochondrial function, and attenuating oxidative stress. Notably, co-therapy shows greater beneficial effects than single treatments. This protective effect appears to involve modulation of key transcription factors regulating lipid and carbohydrate metabolism, as well as influencing endogenous antioxidant defenses. Full article

Adipose tissue functions not only as a lipid storage depot but also as an active endocrine organ that regulates key physiological processes. In obesity, oxidative stress disrupts the molecular pathways for adipose tissue homeostasis, triggering chronic inflammation, tissue dysfunction, and metabolic disorders. This review explores the mechanisms by which lipid storage drives adipose tissue expansion, highlighting the detrimental effects of hypertrophy in promoting oxidative stress, inflammation, and insulin resistance. These processes can ultimately contribute to metabolic pathologies such as cardiovascular diseases and type 2 diabetes. We also discuss how lipid composition influences these pathways, acting as signaling molecules that activate inflammatory and oxidative stress-related signaling cascades. Additionally, we compile evidence from studies on individuals with obesity, identifying lipids, oxidative stress markers, and inflammatory mediators as potential biomarkers of metabolic dysfunction. Finally, we assess the therapeutic potential of antioxidants in mitigating the metabolic effects of obesity, focusing on their mechanisms of actions. By integrating these insights, this review aims to clarify the complex relationship between oxidative stress, lipid metabolism, and inflammation, and highlight the role of antioxidant molecules in addressing adipose tissue dysfunction in obesity. Full article

Exposure to persistent organic pollutants such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD) increases metabolic disorder risk. In this study, we show that a single intraperitoneal injection of TCDD (10 μg/kg) in C57BL/6J mice induced body weight gain, lipid accumulation in the liver and adipose tissue, macrophage infiltration, and elevated hepatic and serum triglyceride levels after 12 weeks. Despite serum aryl hydrocarbon receptor (AhR) ligand levels normalizing by 12 weeks, the persistent effects suggest TCDD sequestration in fat tissue. TCDD inhibited the expression of mitochondrial proteins (COX1, TOM20, TFAM, H2AX) and reduced mitochondrial oxygen consumption. Liver-specific AhR knockout ameliorated TCDD-induced mitochondrial dysfunction, lipid accumulation, and macrophage infiltration. Mechanistically, TCDD-induced hepatic plasminogen activator inhibitor-1 (PAI-1) promoted adipocyte hypertrophy. In the liver, PAI-1 disrupted the interaction between tissue-type plasminogen activator (tPA) and apolipoprotein B (ApoB), thereby enhancing very-low-density lipoprotein (VLDL) assembly. These findings reveal that hepatocyte-derived circulating PAI-1, upregulated via hepatic AhR activation, contributes to adipocyte hypertrophy and hepatosteatosis through the intracellular modulation of the tPA–PAI-1 axis. Thus, hepatic AhR activation drives mitochondrial dysfunction and obesity, even after a single TCDD exposure. Full article