Adipocyte最新文献

Purpose: To evaluate a radiomics-based nomogram using peri-prostatic adipose tissue (PPAT) features for predicting bone metastasis (BM) in newly diagnosed prostate cancer (PCa) patients.

Methods: A retrospective study of 151 PCa patients (October 2010-November 2022) was conducted. Radiomic features were extracted from axial T2-weighted MRI of PPAT, and normalized PPAT was calculated as the ratio of PPAT volume to prostate volume. A radiomics score (Radscore) was developed using logistic regression with 16 features selected via LASSO regression. Independent predictors identified through univariate and multivariate logistic regression were used to construct a nomogram. Predictive performance was assessed using ROC curves, and internal validation involved 1000 bootstrapped iterations.

Results: The Radscore, based on 16 features, showed significant association with BM and outperformed normalized PPAT in predictive value. Independent predictors of BM included Radscore, alkaline phosphatase (ALP), and clinical N stage (cN). A nomogram integrating these factors demonstrated strong discrimination (C-index: 0.908; 95% CI: 0.851-0.966) and calibration, with consistent results in validation (C-index: 0.903; 95% CI: 0.897-0.916). Decision curve analysis confirmed its clinical utility.

Conclusions: Radscore, cN, and ALP were identified as independent BM predictors. The developed nomogram enables accurate risk stratification and personalized BM predictions for newly diagnosed PCa patients.

Obesity lacks physiologically relevant human models, which constrains in-depth investigation into its underlying mechanisms and hampers the development of effective therapeutic strategies for obesity and its associated comorbidities. Here, we developed vascularized adipose organoids (VAOs) from peripheral blood mesenchymal stem cells (PBMSCs) using a standardized three-dimensional dynamic culture system that sequentially induces angiogenesis and adipogenesis. These VAOs mimic native adipose tissue with coexisting adipocytes and endothelial cells. Transcriptomic analysis shows that vascularization alters genes linked to inflammation and redox homoeostasis, yielding distinct metabolic and inflammatory profiles in VAOs versus non-vascularized controls. Notably, upon TNF-α stimulation, VAOs exhibit markedly reduced IL-6 secretion relative to non-vascularized adipose organoids (NVAOs). Importantly, Celastrol simultaneously inhibits angiogenesis and adipogenesis in VAOs and broadly modulates the expression of genes associated with mitochondrial metabolic processes. This study establishes PBMSC-derived VAOs as a scalable, patient-accessible model for investigating adipose development, metabolism, and inflammation. The system also provides a platform for mechanistic research and high-throughput drug screening in obesity and related metabolic diseases.

Acute myocardial infarction (AMI) is a critical condition that induces myocardial ischaemic injury and necrosis, requiring timely intervention to improve outcomes. Emerging evidence suggests that brown adipose tissue (BAT) plays a crucial role in cardiac protection by releasing bone morphogenetic protein 3b (BMP3b), which targets the Smad1/5 pathway in the heart. Here, we investigated whether Electroacupuncture (EA) pretreatment alleviates myocardial injury by activating BAT in AMI mice. The AMI model was established by left coronary artery ligation in male C57BL/6J mice, and EA was applied before AMI model establishment. Comprehensive assessments included morphological and molecular analyses of BAT, cardiac function evaluation, and infarct area measurements. The BMP3b/Smad1/5 signalling pathway was detected in BAT and the heart. Finally, we used mice with scapular BAT removed to verify the pivotal role of BAT in reducing myocardial injury caused by EA. The results showed that EA at ST25 enhanced BAT activation, upregulated BMP3b expression, promoted Smad1/5 phosphorylation, and increased the anti-apoptotic factor Bcl-xL, reducing myocardial damage. However, the protective effect of EA was not observed in the BAT-deficient mice. These findings suggest that EA at ST25 is a promising approach to reduce myocardial injury via the BAT and BMP3b/Smad1/5 pathways.

Adipocytes are abundant in the breast tissue microenvironment. In breast cancer, they can change morphologically according to their proximity to tumour cells, with the closest becoming cancer-associated adipocytes (CAAs). It remains unclear whether breast cancer risk factors, including menopausal status, body mass index (BMI), and mammographic density (MD), influence CAAs morphology in breast carcinogenesis. This study aimed to quantify morphological differences in adipocytes across breast cancer pathologies and associated risk factors. Whole slide images of haematoxylin and eosin stained cancer (n = 149) and normal (n = 182) breast tissue samples were analysed. Parameters representative of adipocyte morphology: perimeter, area, concavity, and aspect ratio, were measured using ImageJ. Adipocytes were considered close (≤2 mm) or distant ( > 2 mm) to cancer cells in cancer samples or breast epithelial cells in normal samples. Close adipocytes in cancer samples were designated CAAs. CAAs decreased in size compared to distant adipocytes (p≤0.0001). A similar trend was observed between close and distant adipocytes in normal (p≤0.0001). CAAs size increased post menopause (p ≤ 0.0001). CAAs size positively correlated with BMI (p ≤ 0.0001). In cancer cases, distant adipocyte size increased and concavity decreased with increasing MD (p ≤ 0.01). Smaller CAAs were associated with poorer survival (p≤0.05). Morphological differences were identified in adipocytes dependent on location within the breast, tissue, pathology and risk factors. Understanding what drives these morphological differences could provide mechanistic insight into whether risk factor-induced alterations in adipocytes influence their role in breast carcinogenesis.

Post-translational modification by the small ubiquitin-like modifier (SUMO) is essential for cellular differentiation and homeostasis. Here, we investigate the role of SUMOylation in adipose tissue development using TAK-981, a pharmacological inhibitor of SUMOylation. Administration of TAK-981 to mice resulted in significant defect in weight gain and adipocyte atrophy in perigonadal white adipose tissue (gWAT) depots. Gene expression analyses revealed a marked downregulation of adipogenic genes, including Pparg, Cebpa, and Fasn. Our data thus indicate that TAK-981 treatment impaired adipogenesis in gWAT, consistent with prior findings that SUMOylation supports transcriptional regulation of adipogenesis and lipid metabolism. We also found significant infiltration of immune cells and efferocytosis in gWAT. Our results thus indicate that SUMOylation inhibition using a small molecule phenocopies genetic hypoSUMOylation models, highlighting its critical role in maintaining adipocyte functionality and immune environment. These findings provide evidence that SUMOylation is essential for fat accumulation in vivo. Furthermore, given that TAK-981 is currently under clinical evaluation for the treatment of solid tumors, our results underscore the importance of considering the potential unintended effects of SUMOylation inhibition on adipose tissue in patients.

Mesenchymal stem cells (MSCs) serve as ideal candidates for a broad range of cell-based therapies. However, cell ageing caused by long-term in vitro expansion and poor survival after in vivo delivery greatly limits their success in preclinical and clinical applications. Dedifferentiation represents a potential strategy for enhancing the retention and function of MSCs in hostile environments. In this study, we evaluated the cell phenotype, proliferation, and differentiation potential, as well as the anti-oxidative stress ability of human umbilical cord-derived MSCs (hMSCs) manipulated with adipogenic priming and subsequent dedifferentiation. After an in vitro differentiation and dedifferentiation procedure, the resultant dedifferentiated hMSCs (De-hMSCs) displayed properties similar to their original counterparts, including immunophenotype and mesodermal potential. Upon re-induction, De-hMSCs exhibited a significantly higher adipogenic differentiation capability than unmanipulated hMSCs. Importantly, De-hMSCs showed a significantly enhanced ability to resist tert-butyl hydroperoxide (t-BHP) induced apoptosis compared to undifferentiated hMSCs. Mechanisms involving bcl-2 family proteins and autophagy may contribute to the demonstrated advantages of dedifferentiation-reprogrammed hMSCs. These results indicate that adipogenic dedifferentiation promotes adipogenesis and cell persistence, as well as preserves the stemness of human umbilical cord-derived MSCs that have been committed to the adipocytic lineage. As a unique stem cell population, dedifferentiated MSCs may represent an attractive and promising candidate for MSC-based therapy.

Evidence suggests that adipose tissue (AT) infiltration in skeletal muscles may negatively influence cardiac function, yet its use as a biomarker remains unclear. This scoping review examined the relationship between AT infiltration and cardiac function in adults. A systematic search of PubMed, CINAHL and SCOPUS identified peer-reviewed studies reporting AT infiltration and cardiac function measures. Excluded were review-type studies, animal studies, abstracts and case series. Study quality was assessed using the Study Quality Assessment Tool (SQAT). Three good-quality studies were included. Findings demonstrated a negative association between AT infiltration and cardiac function parameters, including exercise capacity, left ventricular ejection fraction (LVEF) and heart failure events, in cancer survivors and healthy individuals. There is evidence supporting an association between increased AT infiltration of skeletal muscles and impaired cardiac function, highlighting the need for further research to validate AT infiltration as a potential biomarker. Despite the limited available studies, our findings highlight a distinct association between skeletal muscle AT infiltration and cardiac dysfunction, independent of general obesity.

Mitochondria are essential for generating cellular energy and are significant in the pathogenesis of obesity. Human visceral and subcutaneous preadipocytes (HPA-v and HPA-s) were cultured into mature adipocytes. Intracellular triglyceride (TG) content was assessed using oil-red O staining and tissue triglyceride determination. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were measured with fluorescent indicators. Gene and protein expression related to mitochondrial biogenesis were analyzed by real-time quantitative PCR and Western blotting. Morphological changes were observed via electron microscopy. Results show that PDBSN significantly increased MMP while decreasing TG and ROS levels. The transcription and protein levels of PGC1-α and MTFA were upregulated, and mitochondrial fusion and fission markers (MFN1, MFN2, NRF1, DRP1) were elevated. Additionally, PDBSN enhanced maximum respiratory capacity and reduced ROS. These findings suggest that PDBSN improves mitochondrial function, providing insights for obesity treatment and metabolic disease management.

Obesity is a major global health issue. This study aimed to elucidate its molecular mechanisms by analysing the expression of lncRNAs, miRNAs, and mRNAs in visceral adipose tissue. Through integrated transcriptome sequencing and bioinformatics analysis of obese and normal groups, we observed 118, 92 and 227 differentially expressed lncRNAs, miRNAs and mRNAs, respectively. Functional enrichment analysis revealed these genes were primarily involved in immune response and inflammation-related pathways. A competing endogenous RNA (ceRNA) network was constructed, identifying key interactions among five target genes, including SDC4. Validation confirmed SDC4 was significantly upregulated in obese subjects, and this expression level positively correlated with body mass index and triglyceride. These findings suggest that SDC4 offers the possibility of being a therapeutic target for obesity.

We discovered two adult sisters in Colombia, lineally consanguineous, with severe obesity and undetectable serum leptin levels despite markedly elevated body fat. Their clinical profile included childhood-onset extreme weight gain, intense hunger, hyperphagia, hypogonadotropic hypogonadism, and family history of obesity. Direct sequencing of the LEP gene revealed a novel homozygous missense mutation in exon 3 (c.350G>T [p.C117F]). The presence of this mutation, undetectable leptin, and severe obesity confirmed a diagnosis of monogenic leptin deficiency. Here we describe the clinical outcomes of a 12-month treatment with recombinant human leptin (metreleptin). Metabolic and endocrine assessments were conducted before and after therapy. Metreleptin therapy significantly reduced BMI: from 59 to 38 kg/m² (OBX1, age 27) and 60 to 48 kg/m² (OBX2, age 24). Total body fat mass decreased, serum lipids normalized, and insulin sensitivity improved. Hypogonadotropic hypogonadism reversed, and menstruation resumed. Thus, metreleptin reversed the major metabolic and endocrine abnormalities associated with leptin deficiency in these sisters. Limitations include the small sample size, absence of a control group, and lack of anti-metreleptin antibody measurements. Nevertheless, our findings support that leptin replacement with metreleptin is currently the only effective hormonal treatment for this monogenic form of human obesity.