Search Results (2,950)

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

Various biomaterials are currently employed for dermal biostimulation and filling purposes, with hyaluronic acid (HA)-based fillers among those with the most favorable safety profile, albeit exhibiting a limited biostimulatory effect. This study suggests that hyaluronic acid and succinic acid (SA) can significantly induce beneficial effects on skin cells by targeting key aging hallmarks. Human dermal senescent fibroblasts and aged adipocytes were treated with HA + SA, and various aging characteristics were examined through gene expression analysis and microscopy staining. HA was found to stimulate autophagy gene expression, while SA modulated senescence-gene expression, and the combination of these compounds induced mitophagy in senescent fibroblasts. Additionally, the HA + SA promoted adipogenesis, increased IGF1, and decreased TNFA gene expression in aged adipocytes. Furthermore, the conditioned medium from adipocytes treated with HA + SA upregulated key dermal genes such as COL3A1 and EGF. The findings of this study suggest that HA and SA compounds can be used for the biostimulation of aged skin through the regulation of senescence-associated gene expression and cell communication between dermal fibroblasts and subcutaneous adipocytes. Full article

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

Background/Objectives: The receptor for advanced glycation end products (RAGEs) has been implicated in obesity and metabolic dysfunction. However, its precise role in diet-induced obesity remains unclear. Methods: In this study, we investigated the metabolic consequences of RAGE knockout (RAGE KO) in mice subjected to a Western diet (WD). Results: Our findings demonstrate that RAGE KO mice remained significantly leaner than their wild-type (WT) counterparts when fed a WD, exhibiting reduced body weight gain and smaller adipocyte size. Indirect calorimetry revealed that RAGE KO mice had increased oxygen consumption and locomotor activity compared to WT mice, indicating enhanced energy expenditure. Mitochondrial respiration assays indicated significantly greater oxygen consumption in RAGE KO animals. Additionally, systemic inflammation markers, such as TNF-α, were significantly lower in RAGE KO mice when fed a WD, indicating a reduction in diet-induced inflammatory responses. Conclusions: These findings suggest that RAGE plays a key role in metabolic homeostasis, and its deletion confers resistance to obesity and metabolic disruption induced by a Western diet. Targeting RAGE may provide a novel therapeutic approach for combating obesity and related metabolic disorders. Full article

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Introduction: Although lipomas are common benign tumors found in adults, lipomas of the bladder are extremely rare. Bladder lipomas are infrequently reported in the urologic literature, with only 19 cases published worldwide. These can present as a mass on cystoscopy and cause irritative voiding symptoms, depending on their location. Upon transurethral resection, seeing fat can be concerning for a perforation, as lipoma can be mistaken for extravesical fat. Hence, familiarity with this rare entity is of paramount importance for urologists to prevent unnecessary investigations and interventions that are needed in case of a true bladder perforation. Case presentation: This study presents a case of bladder lipoma in a 73-year-old male with end-stage renal disease who presented for pretransplant urologic evaluation due to microscopic hematuria and irritative lower urinary tract symptoms (LUTS). During cystoscopy, a bladder mass was seen, and a transurethral resection of the bladder tumor (TURBT) revealed bright yellow adipose tissue immediately underneath the bladder mucosa. Concerns about perforation were obviated when seeing intact detrusor muscle underneath, visually confirming the integrity of the bladder wall. The resection was completed, and the CT scan was re-read with the radiologist, which confirmed the presence of a lipoma that was missed pre-operatively due to patient’s oliguria and collapsed bladder. No catheter drainage or cystogram was performed based on these findings. Outcome: The patient healed without any complications. Histopathology confirmed the diagnosis of a mature lipoma. The patient was cleared for transplant from a urologic standpoint and had a successful renal transplantation without delay. Discussion: This case documents the anomalous occurrence of a lipoma within the bladder and supports maintaining a broad differential, including liposarcoma, angiomyolipoma, and other non-malignant fatty tumors during the evaluation of a bladder mass. Full article

Background/Objectives: Estrogen deficiency contributes to dyslipidemia and visceral adiposity, increasing cardiovascular risk in postmenopausal women. Sargassum fulvellum (Sf), a brown seaweed rich in bioactive compounds, possesses lipid-regulating properties that may be enhanced by lactic acid bacteria fermentation. This study aimed to evaluate the effects of fermented S. fulvellum (SfLlLm), prepared using Lactococcus lactis and Leuconostoc mesenteroides, on lipid metabolism and adipose tissue remodeling in an ovariectomized (OVX) mouse model of estrogen deficiency. Methods: Female C57BL/6 mice underwent ovariectomy and were fed an AIN-76A diet supplemented with either unfermented Sf or SfLlLm for eight weeks. Sham-operated and 17β-estradiol-treated OVX groups served as controls. Serum lipid levels—total cholesterol, triglycerides, LDL-C, and HDL-C—were assessed, and histological analysis of visceral adipose tissue was conducted to evaluate adipocyte morphology. Results: OVX-induced estrogen deficiency led to increased total cholesterol, triglycerides, and LDL-C, along with hypertrophic changes in visceral adipocytes. Supplementation with fermented Sargassum fulvellum (SfLlLm) markedly improved these parameters, reducing total cholesterol by 6.7%, triglycerides by 9.3%, and LDL-C by 52.9%, while increasing HDL-C by 17.5% compared to the OVX controls. SfLlLm also normalized visceral adipocyte size and distribution. These effects were comparable to or exceeded those of 17β-estradiol treatment. Conclusions: Fermented SfLlLm ameliorated dyslipidemia and visceral adiposity under estrogen-deficient conditions. These findings support its potential as a functional dietary intervention for managing postmenopausal lipid disorders and associated metabolic complications. Full article

Background: Dyslipidemia and schistosomiasis are major public health challenges, particularly in endemic regions where their coexistence may influence host metabolism and immune responses. This study aimed to evaluate visceral adipose tissue (AT) remodeling in a murine model of acute Schistosoma mansoni infection combined with diet-induced dyslipidemia. Methodology: Female Swiss Webster mice were fed either a standard or high-fat diet (HFD) for 29 weeks and infected with S. mansoni at week 20. Nine weeks after infection, biochemical, morphometric, histopathological, and immunological analyses were performed. Results: The HFD promoted weight gain and dyslipidemia, while S. mansoni infection alone did not alter lipid profiles but partially mitigated the metabolic effects of the HFD. Morphometric analysis revealed adipocyte hypertrophy and reduced cell number in HFD-fed animals. In HFD-fed infected mice, infection partially reversed hypertrophy, suggesting a modulatory effect on AT remodeling. Histopathological examinations showed that while a HFD induced mild inflammation, infection led to intense leukocyte infiltration, hyperemia, and plasma cell degeneration. Peritoneal lavage confirmed a proinflammatory immune profile. Conclusions: These findings indicate that the interaction between a HFD and S. mansoni infection exacerbates adipose tissue inflammation and metabolic alterations, highlighting the complex interplay between parasitic infection, diet, and immune-metabolic regulation. Full article

Xylosyltransferase-I (XT-I) plays a crucial role in skeletal development and cartilage integrity. An XT-I deficiency is linked to severe bone disorders, such as Desbuquois dysplasia type 2. While animal models have provided insights into XT-I’s role during skeletal development, its specific effects on adult bone homeostasis, particularly in human mesenchymal stem cell (hMSC) differentiation, remain unclear. This study investigates how XT-I deficiency impacts the differentiation of hMSCs into chondrocytes, osteoblasts, and adipocytes—key processes in bone formation and repair. The aim of this study was to elucidate for the first time the molecular mechanisms by which XT-I deficiency leads to impaired bone homeostasis. Using CRISPR-Cas9-mediated gene editing, we generated XYLT1 knockdown (KD) hMSCs to assess their differentiation potential. Our findings revealed significant disruption in the chondrogenic differentiation in KD hMSCs, characterized by the altered expression of regulatory factors and extracellular matrix components, suggesting premature chondrocyte hypertrophy. Despite the presence of perilipin-coated lipid droplets in the adipogenic pathway, the overall leptin mRNA and protein expression was reduced in KD hMSCs, indicating a compromised lipid metabolism. Conversely, osteogenic differentiation was largely unaffected, with KD and wild-type hMSCs exhibiting comparable mineralization processes, indicating that critical aspects of osteogenesis were preserved despite the XYLT1 deficiency. In summary, these results underscore XT-I’s pivotal role in regulating differentiation pathways within the bone marrow niche, influencing cellular functions critical for skeletal health. A deeper insight into bone biology may pave the way for the development of innovative therapeutic approaches to improve bone health and treat skeletal disorders. Full article

Background: Obesity is associated with insulin resistance (IR) and characterized by impaired activation of the PI3K/AKT route and glucose uptake. Elevated plasma levels of palmitic acid (PA) diminish insulin signaling in vitro and in vivo. Origanum vulgare L. essential oil (OVEO) is rich in monoterpenes with protective effects against IR. Objective: The study aimed to assess total phenols content and antioxidant activity of OVEO and its cytotoxicity, as well as its effect on insulin signaling and glucose uptake in PA-treated adipocytes. Methods: The quantification of total phenolic content was determined using the Folin–Ciocalteu method, while the antioxidant capacity of OVEO was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods. The cytotoxicity of OVEO (0.1–10 µg/mL) was assessed using the MTS assay. SW872 adipocytes were incubated with 0.4 mM PA for 24 h, with or without a 2 h preincubation of OVEO, and then stimulated with insulin (100 nM, 10 min) or a vehicle. Phosphorylation of Tyr-IRS-1, Ser-AKT, and Thr-AS160 was analyzed by Western blot, and glucose uptake was measured using 2-NBDG. Results: OVEO contained phenols and exhibits antioxidant capacity. All the concentrations of OVEO assessed were not cytotoxic on SW872 adipocytes. PA decreased basal phospho-AS160 as well as insulin-stimulated phospho-IRS1, phospho-AKT, phospho-AS160 and glucose uptake, while OVEO co-treatment enhanced these markers. Conclusions: These findings suggest a beneficial effect of OVEO on the PA-impaired insulin pathway and glucose uptake, which might be explained by its phenolic content and antioxidant capacity, highlighting its potential as a complementary therapeutic agent for IR and related metabolic disorders. Full article

Background: Cucurbitacin E (CuE), a natural tetracyclic triterpenoid compound extracted from the melon stems of Cucurbitaceae plants, has been reported to exhibit anti-inflammatory and anti-cancer properties, along with the ability to enhance cellular immunity. However, its role and molecular mechanism in regulating lipid metabolism and adipogenesis remain unclear. This study aims to investigate the potential anti-adipogenic and anti-obesity effects of CuE in 3T3-L1 adipocytes. Materials and Methods: 3T3-L1 preadipocytes were cultured and induced to differentiate using a standard adipogenic cocktail containing dexamethasone, 3-isobutyl-1-methylxanthine (IBMX), and insulin (DMI). CuE was administered during the differentiation process at various concentrations. Lipid accumulation was assessed using Oil Red O staining, and cell viability was evaluated via the MTT assay. To determine whether CuE induced apoptosis or necrosis, flow cytometry was performed using annexin V/PI staining. Additional molecular analyses, such as Western blotting and RT-PCR, were used to examine the expression of key adipogenic markers. Results: Treatment with CuE significantly reduced lipid droplet formation in DMI-induced 3T3-L1 adipocytes in a dose-dependent manner, as shown by decreased Oil Red O staining. Importantly, CuE did not induce apoptosis or necrosis in 3T3-L1 cells at effective concentrations, indicating its safety toward normal adipocytes. Moreover, CuE treatment downregulated the expression of adipogenic markers such as PPARγ and C/EBPα at both mRNA and protein levels. Discussion: Our findings suggest that CuE exerts a non-cytotoxic inhibitory effect on adipocyte differentiation and lipid accumulation. This anti-adipogenic effect is likely mediated through the suppression of key transcription factors involved in adipogenesis. The absence of cytotoxicity supports the potential application of CuE as a safe bioactive compound for obesity management. Further investigation is warranted to elucidate the upstream signaling pathways and in vivo efficacy of CuE. Conclusions: Cucurbitacin E effectively inhibits adipogenesis in 3T3-L1 adipocytes without inducing cytotoxic effects, making it a promising candidate for the development of functional foods or therapeutic agents aimed at preventing or treating obesity. This study provides new insights into the molecular basis of CuE’s anti-obesity action and highlights its potential as a natural lipogenesis inhibitor. Full article

Abdominal fat necrosis is a dystrophic–necrotic process that is relatively common in dairy cows. It is determined by productive strain (excess fat in the diet), negative energy balance after calving, a lack of physical activity, vitamin E and selenium deficiency, etc. Lipomatous masses are predominantly located in the omentum and mesentery in cattle, potentially causing intestinal obstruction. We report on an outbreak of abdominal fat necrosis that affected 135 of 220 cows and heifers (61.36%); this involved massive fat accumulation in the uterine and salpingian ligaments and severe reproductive disorders (reducing fertility to 20% in cows and 10% in heifers) caused by a hyperenergetic diet (supplementation with saturated fats). A transrectal ultrasound examination of the genital apparatus—both in heifers and in cows in the puerperium—revealed a diffuse pathological hyperechogenicity of the cervical folds, suggesting lipid infiltration, proliferation of the endocervical folds and hyperechogenic lipogranulomas located paracervically or in the uterine ligaments. An ultrasound examination of the ovaries showed the presence of parasalpingial lipogranulomas on the mesovarium, with a uniformly pixelated greasy appearance, that altered the topography of the salpinx, leading to the impossibility of oocyte retrieval. At the histopathological examination, in addition to the necrosis of adipocytes and the subacute–chronic inflammation of the abdominal and retroperitoneal adipose tissue, lipid infiltration of the uterine walls was also observed in the uterine ligaments and lymph nodes. Additionally, lipid infiltration was observed in the wall of the uterine artery. All muscular-type branches of the ovarian artery exhibited subendothelial (subintimal) amyloid deposits, severely reducing their lumen and leading to ischaemia. Amyloidosis was secondary to the systemic inflammatory process triggered by lipid deposition and necrosis. Fertility returned to normal 45–60 days after the exclusion of fat supplements from the diet and their replacement with a vitamin–mineral supplement rich in antioxidants. Full article

Thai fermented soybeans (TFSs) contain phytochemicals with anti-diabetic benefits. In this study, an initial non-optimized TFS extract (TFSE) was prepared using a conventional triplicate 80% ethanol extraction method and evaluated for its biological activity. TFSE effectively reversed TNF-α-induced insulin resistance in 3T3-L1 adipocytes by enhancing insulin-stimulated glucose uptake, indicating anti-diabetic potential. TFSE also upregulated the phosphorylation of AKT (a key insulin signaling mediator) and the expression of adipogenic proteins (PPARγ, CEBPα) in TNF-α-exposed 3T3-L1, suggesting the mitigation of adipocyte dysfunction; however, the results did not reach statistical significance. The conventional extraction process was labor-intensive and time-consuming, and to enhance extraction efficiency and bioactivity, the process was subsequently optimized using environmentally friendly microwave-assisted extraction (MAE) in combination with the Box–Behnken design (BBD) and response surface methodology (RSM). The optimized extract (O-TFSE) was obtained over a significantly shorter extraction time and exhibited higher levels of total flavonoids and antioxidant activity in comparison to TFSE, while showing reduced levels of isoflavones (daidzein, genistein, and glycitein) in relation to TFSE. Interestingly, O-TFSE retained similar efficacy in reversing TNF-α-induced insulin resistance and demonstrated significantly stronger α-glucosidase and α-amylase inhibitory activities, indicating its enhanced potential for diabetes management. These results support the use of MAE as an efficient method for extracting functional compounds from TFS for functional foods targeting insulin resistance and type 2 diabetes mellitus. Full article

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health. Full article

Micro-fragmented adipose tissue (MFAT) is a promising autologous therapy for knee osteoarthritis. To avoid repeated liposuction procedures for its clinical application, MFAT obtained from patients with knee osteoarthritis was stored at −80 °C in a tissue bank. This study describes the preparation, cryopreservation, thawing, and washing, as well as comprehensive analysis of cell populations in fresh and MFAT thawed after two years. Immunophenotyping of both fresh and thawed MFAT showed a significant presence of endothelial progenitors and pericytes in the stromal vascular fraction. Viability before (59.75%) and after freezing (55.73%) showed no significant difference. However, the average cell count per gram of MFAT was significantly reduced in thawed samples (3.00 × 10⁵) compared to fresh ones (5.64 × 10⁵), likely due to processing steps. Thawed MFAT samples showed increased CD73 expression on the CD31^highCD34^high subset of EP and SA-ASC, as well as increased expression of CD105 on EP, the CD31^lowCD34^low subset of EP, pericytes, and SA-ASC. Microbiological testing confirmed 100% sterility, and double washing efficiently removed DMSO, confirming sample safety. Histological analysis revealed healthy, uniformly shaped adipocytes with intact membranes. This approach allows accurate estimation of cell yield for intra-articular injection, ensuring delivery of the target cell number into the knee. Quality control analysis confirms that cryopreserved MFAT retains high cellular and structural integrity, supporting its safety and suitability for clinical application. Full article