Adipocyte最新文献

Stem cell-based therapies are emerging as a promising treatment for diabetes by differentiating these cells into insulin-producing cells (IPCs). However, using growth factors for differentiation has always been challenging. Physical differentiation of stem cells presents a promising approach to reduce reliance on chemical growth factors. One method of physical cell differentiation is cell imprinting. This study aimed to physically induce the differentiation of rat adipose-derived mesenchymal stem cells (rADSCs) into β-like cells using the cell-imprinting technique. For this purpose, RIN-5F cells were used to transfer their geometry and cell-specific topographies to a polydimethylsiloxane (PDMS) substrate. After cell imprinting, the rADSCs were seeded on the substrate, and their differentiation into β-like cells was evaluated after 14 and 21 days by assessing insulin production using dithizone staining and ELISA, as well as real-time PCR and immunocytochemistry (ICC) for expression analysis of the genes effective in cell differentiation into β-like cells, including PDX1, NKX6.1, NGN3, and insulin. The results of dithizone staining and ELISA confirmed insulin secretion by differentiated cells compared to stem cells (p ≤ 0.05). Real-time PCR and ICC results showed that after 21 days, the differentiated cells expressed key β-cell genes significantly more than stem cells (p ≤ 0.05).

Brown and beige adipose tissue represent evolutionary adaptations in mammals, functioning as specialized thermogenic organs to maintain body temperature. Over the past two decades, researches have demonstrated that white adipose tissue (WAT) browning is an effective strategy to enhance energy expenditure. However, a growing body of evidence indicates that the browning process frequently occurs in a variety of chronic disease states, though its pathophysiological significance remains unclear. This review summarized evidence of pathological browning observed in human diseases and animal models, including breast cancer, colorectal cancer (CRC), clear cell renal cell carcinoma (ccRCC), kidney health, burn injury, atherosclerotic, SARS-CoV-2 and sepsis. Despite distinct pathological contexts, adipose tissue browning is consistently observed. This suggests that browning may not simply serve its classical metabolically protective role, but instead reflect an atypical response to pathological stress. It is currently unclear whether this is a compensatory mechanism by the organism in a diseased state or merely a byproduct of the disease process. Whether this response is adaptive or a cause of disease progression remains unresolved. Future research should therefore focus on identifying the triggers and functional outcomes of pathological browning to better understand adipocyte plasticity and its role in disease progression.

Adipose omeostasishomoeostasis is maintained through the precise coordination of lipogenesis, lipolysis, and adipocyte differentiation, with microenvironmental components dynamically regulating lipid metabolism. Even though the classical cAMP-PKA pathway has been well-characterized for its function in lipid metabolism by phosphorylating transcription factors and lipolytic enzymes, little is known about how it collaborates with elements of the adipose tissue microenvironment, such as immune cells and the vascular endothelium, especially in pathological situations like obesity. EPAC, a newly discovered cAMP effector, has shown new signalingsignallingsignalling signalling pathways in the immune and cardiovascular systems by activating small G proteins. However, there are important understanding gaps regarding its roles in adipose metabolism, namely adipocyte development, microenvironmental interaction, and the pathophysiology of metabolic diseases. By bringing together disparate studies on PKA and EPAC, this review provides the first comprehensive synthesis of the cAMP-PKA/EPAC dual signaling signalling signallingcins signalling network, filling in knowledge gaps. The reciprocal regulation between this signaling signalling signalling signalling network and the adipose microenvironment establishes a novel 'signaling-microenvironment-systemic metabolism' framework for understanding metabolic disorders, including obesity, diabetes, and hepatic steatosis. Pharmacological modulation of the PKA/EPAC signalingsignalling signalling signalling pathways may therefore represent a viable therapeutic approach for restoring adipose tissue homeostasis homoeostasis.

Erianin, a natural bibenzyl compound, has recently garnered attention owing to its diverse biological activities. In the present study, we investigated the effects of Erianin on adipocyte differentiation, lipid metabolism, and mitochondrial respiration in murine 3T3-L1 cells. Cytotoxicity assays indicated that Erianin exhibited low toxicity towards preadipocytes at concentrations up to 200 μM. Treatment with 20 μM Erianin completely inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes and reduced lipid droplets. Western blot analysis revealed that Erianin attenuated Akt and p38 MAPK signalling without inducing apoptosis, suppressed the expression of key pro-adipogenic transcription factors, C/EBPα and PPARγ during the early stages of differentiation. This suppression was accompanied by the downregulation of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), pyruvate carboxylase (PC) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). While early-stage differentiation was robustly inhibited, higher concentrations (≥25 μM) were required to suppress terminal differentiation of immature adipocytes. This late-stage inhibition was accompanied by decreased expression of PPARγ, PC, and HMGCR, with minimal effects on ACC1 and FASN, suggesting a more modest role for Erianin in terminal adipogenesis. Assessment of mitochondrial metabolism of 3T3-L1 cells following 24-hour treatment of Erianin showed that it modestly impaired ATP-linked respiration, maximal respiration, spare respiratory capacity and intracellular ATP levels while basal respiration was unaffected. Collectively, these findings indicated that Erianin predominantly targets early adipogenic differentiation and mitochondrial bioenergetics.

The receptor for advanced glycation end products (RAGE) and its ligands are critical drivers of adipose tissue inflammation. While RAGE expression increases in ageing cells and pathological conditions, its specific role in high-fat diet (HFD)-induced adipose tissue senescence remains to be fully elucidated. In this study, we investigated the function of RAGE in the development of adipose tissue senescence associated with obesity. We observed that HFD-fed RAGE-deficient (RAGE^-/-) mice exhibited significantly reduced body weight and adipocyte hypertrophy compared to wild-type (WT) controls. At the molecular level, RAGE^-/- mice displayed lower mRNA expression of cell cycle regulators and markers of the senescence-associated secretory phenotype. This anti-senescent phenotype was accompanied by decreased reactive oxygen species (ROS) production and elevated expression of anti-oxidant genes. Mechanistically, the lack of RAGE resulted in the upregulation of silent information regulator type 1 (SIRT1) in adipose tissues. Notably, the inhibition of SIRT1 reversed these anti-senescent effects and attenuated anti-oxidant gene expression in RAGE-deficient mice. Furthermore, while antioxidant treatment with N-acetylcysteine (NAC) reduced p53 in WT mice, it failed to fully suppress p16 and p21, whereas NAC treatment in RAGE^-/- mice significantly downregulated all senescence markers, suggesting a synergistic protective effect. In conclusion, our results demonstrated that RAGE deficiency improved anti-oxidant properties and prevents adipocyte senescence via the SIRT1 signalling pathway, highlighting a potential therapeutic target for obesity-associated tissue dysfunction.

The objective of this study was to identify key secretory protein-encoding differentially expressed genes (SP-DEGs) in adipose tissue in female metabolic syndrome, thus detecting potential targets in treatment. We examined gene expression profiles in 8 women with metabolic syndrome and 7 healthy, normal body weight women. A total of 143 SP-DEGs were screened, including 83 upregulated genes and 60 downregulated genes. GO analyses of these SP-DEGs included proteolysis, angiogenesis, positive regulation of endothelial cell proliferation, immune response, protein processing, positive regulation of neuroblast proliferation, cell adhesion and ER to Golgi vesicle-mediated transport. KEGG pathway analysis of the SP-DEGs were involved in the TGF-beta signalling pathway, cytokine‒cytokine receptor interactions, the hippo signalling pathway, Malaria. Two modules were identified from the PPI network, namely, Module 1 (DNMT1, KDM1A, NCoR1, and E2F1) and Module 2 (IL-7 R, IL-12A, and CSF3). The gene DNMT1 was shared between the network modules and the WGCNA brown module. According to the single-gene GSEA results, DNMT1 was significantly positively correlated with histidine metabolism and phenylalanine metabolism. This study identified 7 key SP-DEGs in adipose tissue. DNMT1 was selected as the central gene in the development of metabolic syndrome and might be a potential therapeutic target.

Obesity is characterized by macrophage infiltration into adipose tissue. White adipose tissue remodelling under inflammatory conditions involves both hypertrophy and adipogenesis and is regulated by transcription factors, which are influenced by bone morphogenetic protein (BMP) signalling. MicroRNAs (miRNAs) regulate gene expression and are involved in obesity-related processes such as adipogenesis. Therefore, we identified differentially expressed miRNAs in the epididymal white adipose tissue (eWAT) of mice fed a normal diet (ND) and those fed a high-fat diet (HFD). The expression of miR-6402 was significantly suppressed in the inflamed eWAT of HFD-fed mice than in ND-fed mice. Furthermore, Bmpr2, the receptor for BMP4, was identified as a target gene of miR-6402. Consistently, miR-6402 was downregulated in the inflamed eWAT of HFD-fed mice and in 3T3-L1 cells (preadipocytes) and differentiated 3T3-L1 cells (mature adipocytes) , and BMPR2 expression in these cells was upregulated. Adipogenesis was induced in WAT by BMP4 injection (in vivo) and in 3T3-L1 cells by BMP4 stimulation (in vitro), both of which were inhibited by miR-6402 transfection. Inflamed eWAT showed higher expression of BMPR2 and the adipogenesis markers C/EBPβ and PPARγ, which was suppressed by miR-6402 transfection. Our findings suggest that miR-6402 is a novel anti-adipogenic miRNA that combats obesity by inhibiting the BMP4/BMPR2 signalling pathway and subsequently reducing adipose tissue expansion.

The aim of this study was to create and validate a high-throughput method based on open-source software for the measurement of adipocyte diameters in white adipose tissue histological sections. Human omental and subcutaneous adipose tissue samples collected during bariatric surgery were used to prepare haematoxylin and eosin-stained histological slides. Adipocyte diameters were measured both manually and with an automated procedure created using ImageJ. Comparative analysis of our automated method with the manual measurement and associations of the mean adipocyte diameters with cardiometabolic markers were used to validate our method. A total of 377 adipose samples (190 participants) were included in the analysis. Pearson correlation of mean adipocyte diameters showed a strong linear relationship between methods (r = 0.87, p < 0.0001). Omental adipocyte diameters of both methods were significantly associated with the same markers of cardiometabolic risk (fasting concentrations of TG, HDL-Chol, homoeostasis model assessment of insulin resistance, and visceral adiposity index values) with no significant differences between methods. There were also no significant differences between the manual and automated method regarding the correlations between mean subcutaneous adipocyte diameters and anthropometric or metabolic markers. In conclusion, we have created and validated a rapid automated method to measure adipocyte diameters from whole-slide adipose tissue images.

Coronavirus disease 2019 (COVID-19) is more severe in obesity. A cytokine storm was observed in critically ill patients. Since adipose tissue secretes cytokines, we investigated whether cytokines mediate the effect of obesity on COVID-19 severity. Using replicated two-sample Mendelian randomization analyses, we assessed the causal effect of body mass index (BMI) on COVID-19 severity. We evaluated the BMI effect on 41 inflammatory cytokines, JAK-2, lymphocyte percentage and leptin. We tested the relationship between these immunological factors and COVID-19 severity and conducted mediation analysis.Higher BMI increased the risk of COVID-19 severity. BMI was causally associated with five inflammatory cytokines - HGF, TRAIL, IL-13, IL-6, and IL-7 - with replication confirming these associations. TNF-α and IL-8 were identified as associated with COVID-19 severity, but with no replication support. Leptin-related genetic variation was associated with COVID-19 severity and supported by replication, but JAK-2 and lymphocyte percentage provided no evidence of association. None of the immunological factors tested showed consistent statistical evidence of mediation between BMI and COVID-19 severity. Our findings support the reported causal association between BMI and COVID-19 severity. Although several cytokines elevated due to higher BMI, we observed inconsistent evidence for baseline cytokines levels increasing COVID-19 severity. Baseline levels of circulating cytokines, JAK-2, lymphocyte percentage, and leptin showed no evidence of mediating the BMI and severe COVID-19 link. Limited participants in cytokine GWASs reduce statistical power, and missing population data on cytokine responses to infection are major limitations requiring resolution to explain cytokines' mediating role between BMI and severe COVID-19.

White adipose tissue (WAT) browning has gained increasing attention as potential strategy for obesity management. The conversion of WAT into brown adipose tissue (BAT) enhances energy expenditure and improves metabolic health. Propolis, natural resinous substance produced by honeybees, contains bioactive compounds such as caffeic acid phenethylester, chrysin and quercetin, which are thought to regulate adipogenesis and promote WAT browning. This systematic review aimed to synthesize preclinical evidence on the molecular mechanisms by which propolis and its bioactive compounds regulate adipogenesis, lipid metabolism and the browning of white adipose tissue. We conducted a systematic search of electronic databases, including PubMed, Scopus and Google Scholar, without time restrictions, using relevant keywords related to propolis and obesity. A total of 7 preclinical studies (animal and in vitro) met the inclusion criteria. These studies indicate that propolis and its bioactive compounds, modulate adipogenic transcription factors, reduce lipid accumulation and increase expression of browning markers in cellular and animal models. Studies in vivo demonstrate reductions in body weight, fat accumulation and adipocyte differentiation, accompanied by increased thermogenesis. Preclinical evidence suggests that propolis modulates adipogenesis, lipid metabolism and WAT browning; however, clinical trials assessing mechanistic endpoints are lacking and necessary before translational recommendations can be made.