Search Results (910)

Adipose tissue renewal requires precise coordination of stem/progenitor cell proliferation, preadipocyte commitment, and terminal adipocyte differentiation. T-cadherin (CDH13), an atypical GPI-anchored cadherin, is expressed in adipose tissue and functions as a receptor for high-molecular-weight (HMW) adiponectin—a key adipokine produced by adipose tissue and involved in metabolic regulation. While T-cadherin is implicated in cardiovascular and metabolic homeostasis, its role in adipogenesis still remains poorly understood. In this study, we used the 3T3-L1 preadipocyte model to investigate the function of T-cadherin in adipocyte differentiation. We analyzed T-cadherin expression dynamics during differentiation and assessed how T-cadherin overexpression or knockdown affects lipid accumulation, expression of adipogenic markers, and key signaling pathways including ERK, PI3K–AKT, AMPK, and mTOR. Our findings demonstrate that T-cadherin acts as a negative regulator of adipogenesis. T-cadherin overexpression ensured a proliferative, undifferentiated cell state, delaying early adipogenic differentiation and suppressing both lipid droplet accumulation and the expression of adipogenic markers. In contrast, T-cadherin downregulation accelerated differentiation, enhanced lipid accumulation, and increased insulin responsiveness, as indicated by PI3K–AKT pathway activation at specific stages of adipogenesis. These results position T-cadherin as a key modulator of adipose tissue plasticity, regulating the balance between progenitor expansion and terminal differentiation, with potential relevance to obesity and metabolic disease. Full article

IMF is a key determinant of meat quality, influencing tenderness, juiciness and flavor, yet the mechanisms underlying its formation remain poorly understood. Previous studies performed whole-genome resequencing and GWAS on pigs with divergent IMF content, identifying MCEE as a candidate gene associated with IMF deposition. Subsequently, gain- and loss-of-function approaches were employed to investigate the role of MCEE in porcine intramuscular preadipocytes. Here, we isolated primary preadipocytes and subjected them to adipogenic induction. The overexpression of MCEE enhanced the proliferation and adipogenic differentiation of porcine intramuscular preadipocytes, whereas its knockdown exerted the opposite effect. Transcriptomic analysis revealed that DEGs were primarily enriched in pathways related to oxidative phosphorylation, mitochondrial dysfunction-associated disorders and others. Subcellular localization prediction indicated mitochondrial targeting of MCEE, and its expression level influenced mitochondrial function, including reactive oxygen species levels, mitochondrial membrane potential and permeability transition pore opening. Collectively, MCEE regulates IMF deposition by modulating mitochondrial function, and these findings provide a potential molecular target for improving meat quality. Full article

Single three-lactic acid bacterial strains with anti-adipogenic effects in C3H10T1/2 cells and possessing beneficial probiotic properties were administered to mice fed a high-fat diet. Of the three strains, Lactiplantibacillus plantarum RP12, which had the lowest weight gain, was utilized for further studies, including a second mouse experiment lasting 10 weeks. Oral administration of Lactiplantibacillus plantarum RP12 resulted in reduced body weight gain and epididymal fat mass. Significant reductions in serum total cholesterol, triglycerides, and blood glucose were observed in the group treated with Lactiplantibacillus plantarum RP12. This strain was found to regulate the expression of genes associated with lipid metabolism in epididymal adipose tissue and liver. It induced changes in the composition of fecal microbiota. Although there is no difference in the Bacillota to Bacteroidota ratio between the HFD and RP12 groups, notable differences in the compositions at the family, genus, and species levels were evident. Specifically, differences in the proportions of some taxa reported to have an association with obesity were observed between the HFD and RP12 groups. Fecal analyses demonstrated that Lactiplantibacillus plantarum RP12 diminishes lipid absorption and augments the production of short-chain fatty acids in the intestine. Lactiplantibacillus plantarum RP12 also mitigated damage to the morphology of the ileum and colon caused by a high-fat diet and promoted the expression of Claudin-1 and Muc2. Overall, Lactiplantibacillus plantarum RP12 has potential as a useful probiotic to address metabolic disorders as well as obesity, substantiating the positive in vivo indicators and modulation of gut microbiota in a high-fat diet-induced obese mouse model. Full article

The objective of this review was to critically evaluate the available literature on the development of periodontal ligament organoids. Articles concerning periodontal ligament organoids were considered eligible. References were selected in a two-phased process. Electronic databases PubMed and Scopus were screened up to June 2024, yielding 1101 studies. After removing duplicates, titles, and abstracts were screened, resulting in 44 articles being included in this review. A detailed analysis of the included articles was organized into four categories: (1) the cell lineages used, including the simultaneous use of two or more cell types, (2) the extracellular matrix composition, (3) the organoid preparation methods, and (4) the characterization techniques employed. The main findings show that collagen combined with biodegradable polymers—such as poly(caprolactone), poly(glycolic acid), and poly(lactic acid)—is the most used material. Periodontal ligament cells and periodontal fibroblasts were the most used cell types, due to their role in extracellular matrix remodeling. The most frequent analyses performed included alkaline phosphatase, extracellular matrix mineralization, and gene expression, providing insights into differentiation and periodontal regeneration. Cementogenic differentiation was the most studied, followed by osteogenic, chondrogenic, adipogenic, and epithelial differentiation. However, challenges remain, including methodological inconsistencies and the need for scaffold optimization. Future research should focus on standardizing protocols, improving biomaterials, and integrating bioprinting techniques to improve clinical translation. Full article

The effects of Δ⁹-tetrahydrocannabinol (THC) on adipocyte function under obesogenic, free-fatty-acid (FFA)-rich conditions remain poorly characterized, particularly regarding adipogenesis, FFA buffering, and downstream hepatocyte lipid handling. We investigated THC’s effect on adipogenic differentiation, temporal FFA buffering in mature adipocytes under lipid stress, and hepatocyte lipid accumulation driven by extracellular FFAs. The 3T3-L1 preadipocytes were differentiated in 0.5 mM oleate: palmitate (2:1) medium with vehicle (EtOH), THC (1 μM), or rosiglitazone (30 μM). Adipogenesis was assessed using BODIPY/NucSpot 650 staining followed by lipid droplet (LD) analysis. Adipocytes (days 10–18) were monitored for lipid accumulation, LD morphology, lipolysis, extracellular non-esterified fatty acids (NEFA), and lipid-handling gene expression. Conditioned media (CM) were applied to AML12 hepatocytes to assess lipid uptake. By day 6, THC enhanced adipogenesis, increasing lipid accumulation. In mature adipocytes, THC induced a biphasic buffering response: on day 10, NEFA levels were elevated despite unchanged lipid content, with increased isoproterenol-stimulated lipolysis. By day 18, buffering improved, with enhanced lipid storage, elevated stimulated lipolysis, smaller LDs, and altered gene expression. AML12 lipid accumulation corresponded with residual NEFA in CM, indicating that adipocyte FFA sequestration modulates hepatocyte lipid uptake. These findings reveal that under FFA-rich conditions, THC promotes late-stage adipogenesis and remodels adipocyte lipid handling, regulating extracellular FFA availability and hepatocyte lipid loading. Full article

Primary cells better reflect the physiological situation, and mesenchymal stromal cells (MSCs), especially, are promising candidates for biomedical applications. MSCs from the umbilical cord (UC) can be collected easily, non-invasively, and painlessly and do not involve ethical problems. The derived cell products harbor great potential in stem cell technology and agricultural applications. A tissue grinder (TIGR) was used to homogenize porcine UC tissue and to dissociate the UC cells, thereby testing different tissue-to-medium ratios. Cells were cultivated until passage 3, and the proliferation rate, metabolic activity, colony forming ability, surface marker expression, and multi-lineage differentiation potential were assessed. Tissue grinding could be successfully used to isolate UC-derived porcine cells with a high yield and viability, as well as an increasing proliferation rate during cultivation. Isolated cells showed MSC-like features: the expression of CD73, CD90, and CD105, ability to form colonies, and adipogenic, chondrogenic, and osteogenic differentiation. Tissue grinding is highly suitable for isolating high-quality cells from whole UC tissue of pigs in a fast and reproducible way. Cells might be used in a wide range of therapeutical and biotechnological applications, such as understanding and treating severe disorders, drug screening, or tissue engineering. Cells from supposedly waste tissues like UC will be especially useful in transplantation medicine. Full article

Background: Obesity is a global health issue closely associated with dysregulated lipid metabolism and chronic inflammation. Effective strategies targeting both lipogenesis and inflammation are essential for managing obesity and its related metabolic disorders. Methods: This study evaluated the effects of Terminalia catappa Linn. leaf extract (TCE) on lipogenic and lipolytic pathways in high-fat diet (HFD)-induced obese mice. UPLC-QTOF-MS analysis was conducted to identify and quantify the major phenolic compounds in TCE. Mice were administered low and high doses of TCE, and various metabolic parameters, including lipid profiles, liver function markers, adipokine levels, and gene/protein expressions related to lipid metabolism and inflammation, were assessed. Results: UPLC-QTOF-MS analysis identified four major phenolic compounds in TCE—gallic acid, orientin, vitexin, and ellagic acid—with respective contents of 112.5, 163.3, 184.7, and 295.7 mg/g extract. TCE administration significantly reduced liver and adipose tissue weights, along with hepatic and adipose lipid accumulation. Both low and high doses of TCE markedly lowered serum lipid levels. Liver function was improved, as indicated by reduced levels of AST, ALT, and ALP, while BUN levels remained unchanged. On the molecular level, TCE downregulated adipogenic and lipogenic genes (PPARγ, PPARα, C/EBPα, aP2) and upregulated metabolic regulators, including leptin, adiponectin, p-HSL/HSL, and p-perilipin/perilipin, without affecting ATGL expression. TCE also suppressed pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and TGFβ-1. Conclusions: These findings highlight the therapeutic potential of TCE in managing obesity by inhibiting lipogenesis, enhancing lipolysis, and reducing inflammation. Full article

Concentrated growth factor (CGF) is an autologous blood-derived product widely used in regenerative medicine due to its high concentration of growth factors and platelets. In this study, the ability of primary stem cells isolated from human CGF to differentiate into adipocytes, endothelial cells, and neuronal-like cells was evaluated in vitro. CGF primary cells (CPCs) were obtained from CGF fragments and characterized after one month in culture. These cells were positive for the surface markers CD105, CD45, CD31, and CD14, and also expressed mRNA levels of the stemness markers Nanog and Oct3/4 comparable to human bone marrow mesenchymal stem cells (BMSCs). Results showed that, following appropriate differentiation protocols, CPCs, similarly to BMSCs, were able to differentiate into adipogenic, endothelial, and neuronal lineages, acquiring specific phenotypic and molecular markers. Adipogenic induction resulted in lipid accumulation and the upregulation of key genes, including PLIN2, FABP4, CD36, and FASN. Under pro-endothelial conditions, the cells exhibited increased expression of endothelial markers, eNOS, VEGFR-2, and CD31. Neuronal induction promoted the expression of β-tubulin III, Nestin, and Neurofilament. Overall, this work highlights the remarkable plasticity of CPCs and supports their potential application in multilineage regenerative therapies. Full article

In individuals with non-adipogenic traits and enhanced ketogenic capacity, plasma triglyceride (TG) levels are typically low, while low-density lipoprotein cholesterol (LDL-C) levels often exceed the normal range, complicating cardiovascular risk assessment. We analyzed lipid profiles to better characterize cardiovascular risk in this population. Drug-naïve patients newly diagnosed with prediabetes or type 2 diabetes (T2D) were divided into two groups based on serum β-hydroxybutyrate levels: enhanced versus non-enhanced ketogenesis. Among those with enhanced ketogenesis, 27 individuals with high LDL-C (≥100 mg/dL) and low TG (<150 mg/dL) were selected. For comparison, 27 individuals with high TG (>150 mg/dL) from the non-enhanced group were included. The enhanced ketogenesis group demonstrated more favorable lipid characteristics, including a significantly larger average LDL particle size (26.8 ± 0.3 nm vs. 25.9 ± 0.6 nm, p < 0.001), a lower proportion of small dense LDL particles, and reduced oxidized LDL to LDL-C ratio. Importantly, enhanced ketogenesis remained an independent predictor of larger LDL particle size after adjusting for potential confounders including TG. Despite the potential of selection bias intentionally induced by the predefined inclusion criteria, our findings suggest that patients with T2D or prediabetes who exhibit enhanced ketogenesis, even in the presence of elevated LDL-C levels, may have a more favorable atherogenic profile and are not necessarily at increased cardiovascular risk. Full article

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) profoundly disrupt lipid metabolism within local microenvironments of skeletal muscle and its associated connective tissues, including adipose tissue, bone, and fascia. However, the role of local communication between skeletal muscle and its proximal connective tissues in propagating metabolic dysfunction is incompletely understood. This narrative review synthesizes current evidence on these local metabolic interactions, highlighting novel insights and existing gaps. Methods: We conducted a comprehensive literature analysis of primary research published in the last decade, sourced from PubMed, Web of Science, and ScienceDirect. Studies were selected for relevance to skeletal muscle, adipose tissue, fascia, and bone lipid metabolism in the context of obesity and T2DM, with emphasis on molecular, cellular, and paracrine mechanisms of local crosstalk. Findings were organized into thematic sections addressing physiological regulation, pathological remodeling, and inter-organ signaling pathways. Results: Our synthesis reveals that local lipid dysregulation in obesity and T2DM involves altered fatty acid transporter dynamics, mitochondrial overload, fibro-adipogenic remodeling, and compartment-specific adipose tissue dysfunction. Crosstalk via myokines, adipokines, osteokines, bioactive lipids, and exosomal miRNAs integrates metabolic responses across these tissues, amplifying insulin resistance and lipotoxic stress. Emerging evidence highlights the underappreciated roles of fascia and marrow adipocytes in regional lipid handling. Conclusions: Collectively, these insights underscore the pivotal role of inter-tissue crosstalk among skeletal muscle, adipose tissue, bone, and fascia in orchestrating lipid-induced insulin resistance, and highlight the need for integrative strategies that target this multicompartmental network to mitigate metabolic dysfunction in obesity and T2DM. Full article

Periodontal therapy remains a complex task in dentistry as current methodologies often tend to induce tissue repair rather than regeneration. Caffeine is an alkaloid found in multiple natural sources, which has been reported to have multiple beneficial effects, such as promoting adipogenic differentiation, a key factor in tissue regeneration. Unfortunately, it has also been reported to decrease cell viability and reduce osteogenic and chondrogenic differentiation, both of which play an important role in regenerative medicine. In this study, we aimed to find a non-cytotoxic dose of purified caffeine over dental pulp stem cells (DPSCs) that could provide its beneficial effects over adipogenesis, while reducing the negative effect upon osteogenesis and chondrogenesis. Additional experiments were conducted to determine its impact upon the expression of pro-inflammatory enzymes, and antibacterial assays to assess a potential antibacterial effect. The results attested that purified caffeine at a dose of 8.03 μM holds no viability reduction effect, nor has any impact on the expression of pro-inflammatory enzymes, promotes adipogenic differentiation, and does not negatively affect osteogenic or chondrogenic differentiation, with any antibacterial effect against Streptococcus mutans, Escherichia coli, and Staphylococcus aureus. These findings suggest that purified caffeine at a dose of 8.03 μM has the potential to aid in the field of regenerative dentistry. Full article

Background: Postbiotics with anti-adipogenic properties can significantly modify adipocyte metabolism by influencing key cellular pathways involved in lipid accumulation. In preliminary in vitro studies, it is essential to monitor various cellular and subcellular variables, including gene expression and protein synthesis potential, through RT-qPCR analysis. It is also crucial to select internal controls carefully and evaluate their stability for effective normalization and accurate interpretation of the results. Methods: In this study, we assessed the stability of six commonly used housekeeping genes: GAPDH, Actb, HPRT, HMBS, 18S, and 36B4. We analyzed their variability in mature 3T3-L1 adipocytes treated with supernatants from newly isolated Lacticaseibacillus paracasei strains. Our analysis combined classical statistical methods, a ∆Ct analysis, and software algorithms such as geNorm, NormFinder, BestKeeper, and RefFinder. Results: Our stepwise, multiparameter strategy for selecting reference genes led to the exclusion of Actb and 18S as the most variable reference genes. We identified HPRT as the most stable internal control. Additionally, HPRT and HMBS emerged as a stable pair, while the recommended triplet of genes for reliable normalization consists of HPRT, 36B4, and HMBS. Conclusions: The widely used putative genes in similar studies—GAPDH and Actb—did not confirm their presumed stability, which once again emphasizes the need for experimental validation of internal controls to increase the accuracy and reliability of gene expression. Combining a unique biological model—postbiotic-treated adipocytes—with multiple algorithms integrated into a single workflow allows us to provide a methodological template applicable to similar nutritional and metabolic research settings. Full article

Endometrial mesenchymal stem cells (eMSCs) are a novel and biologically potent source of multipotent stromal cells with potential beyond reproductive medicine. This study explored their phenotypic profile, trilineage differentiation, and the cytoprotective effects of their conditioned media (eMSCCM) on oxidatively stressed neonatal and adult chondrocytes. Canine eMSCs displayed typical fibroblast-like morphology and expressed high levels of mesenchymal surface markers CD29 and CD44, low hematopoietic markers CD34/CD45, and variable CD90, confirming a mesenchymal identity. Differentiation assays revealed osteogenic and chondrogenic differentiation, whereas adipogenic activity was limited. Using eMSCCM at 25% and 50% concentrations, chondrocyte viability was assessed after exposure to 200 µM H₂O₂. eMSCCM significantly enhanced the viability of H₂O₂-stressed chondrocytes in a dose-dependent manner, particularly at 50%, with marked effects at 24 and 48 h. Although metabolic activity declined at 72 h, the treated cells remained more metabolically active than untreated controls. These findings suggest that eMSCCM offers promising cytoprotective effects for cartilage-related oxidative stress conditions. Full article

Adipose tissue development plays a critical role in determining carcass quality and meat production efficiency in swine; however, the regulatory mechanisms governing fat deposition remain incompletely understood. Circular RNAs (circRNAs), characterized by high stability and resistance to RNase R degradation, have emerged as important epigenetic regulators of livestock traits. This study investigated the regulatory role of circIDH2 in adipogenic differentiation of porcine preadipocytes and the underlying molecular mechanisms. Functional assays revealed that silencing circIDH2 markedly promoted preadipocyte proliferation while inhibiting differentiation and lipid accumulation; conversely, circIDH2 overexpression produced the opposite effects. Mechanistically, circIDH2 acted as a molecular sponge for miR-193a-5p through complementary base pairing, thereby relieving the repression of its target gene RASGRP4, a positive regulator of adipogenesis. Furthermore, this study demonstrated that miR-193a-5p promoted proliferation but suppressed the differentiation of porcine preadipocytes, whereas RASGRP4 inhibited proliferation while promoting adipogenic differentiation. Rescue experiments further confirmed the regulatory relationship among circIDH2, miR-193a-5p, and RASGRP4. In summary, the findings indicated that circIDH2 functioned as a key regulator of adipogenesis by modulating the miR-193a-5p/RASGRP4 axis, thereby suppressing preadipocyte proliferation and promoting adipogenic differentiation. These results provide a theoretical foundation for future investigations into the regulatory mechanisms of adipose tissue development. Full article