AdipocytePub Date : 2026-12-31Epub Date: 2026-09-27DOI: 10.1080/21623945.2026.2737919
Sonja Großmann, Petra Waldegger, Tina Deutinger, Werner Zwerschke
{"title":"The extracellular matrix protein SNED1 affects self-renewal, proliferation and adipogenic differentiation of human adipose stem/progenitor cells.","authors":"Sonja Großmann, Petra Waldegger, Tina Deutinger, Werner Zwerschke","doi":"10.1080/21623945.2026.2737919","DOIUrl":"10.1080/21623945.2026.2737919","url":null,"abstract":"<p><p>The fate of adipose stem/progenitor cells (ASCs) is influenced by the extracellular matrix (ECM). However, the interaction between ASCs and components of the ECM in human white adipose tissue (WAT) is not precisely understood. The gene Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1) encodes a secreted ECM glycoprotein of unknown function in AT. In the present study, we show that knockdown of the SNED1 expression in ASCs leads to a significantly reduced self-renewal and proliferation capacity; moreover, the adipogenic differentiation potential is reduced. Our data suggest that SNED1 contributes to a functional interaction between ECM and ASCs, which is important for stemness and commitment to proliferation and differentiation in adult adipose stem/progenitor cells.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2737919"},"PeriodicalIF":3.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-31Epub Date: 2026-05-12DOI: 10.1080/21623945.2026.2671558
Erica de Sousa, Magdalena Blaszkiewicz, Kristy Townsend
{"title":"A non-invasive method for light-inducible knockout across all cell types in mouse subcutaneous adipose tissue.","authors":"Erica de Sousa, Magdalena Blaszkiewicz, Kristy Townsend","doi":"10.1080/21623945.2026.2671558","DOIUrl":"10.1080/21623945.2026.2671558","url":null,"abstract":"<p><p>Cre recombination is a widely used technique for mechanistic insights in physiology and disease. However, available constitutive and inducible Cre systems present challenges that can be prohibitive for some study designs. For example, Cre expression can result in cell types targeted across numerous tissues and organs, or when a gene is expressed across multiple cell types in a tissue, Cre-Lox restricted knockout will not enable ablation across an entire tissue or organ. Photoactivatable Cre (PA-Cre) systems enable temporally and spatially restricted gene expression control in delimited anatomical regions, typically requiring a micro-LED or fibre optic implantation. Here, we report as proof-of-concept the effective knockout of BDNF in subcutaneous adipose tissue after PA-Cre activation through external blue light illumination in awake, freely moving mice. We demonstrated that for mice with black fur, shaving can be used to anatomically limit PA-Cre activation. BDNF protein expression was decreased by 87% in the inguinal scWAT after blue light exposure, with no effect observed in the perigonadal (deep) or axillary subcutaneous (non-shaved) adipose tissues. We propose blue light induction of PA-Cre as safe and effective to study adipose tissue physiology and pathology across models. Considerations for applying this tool to future studies are also presented.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2671558"},"PeriodicalIF":3.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13170378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-01Epub Date: 2026-08-20DOI: 10.1080/21623945.2026.2719267
Deborah Scherkamp, Victoria Wachenfeld-Teschner, Larissa Rabe, Fábio Dos Santos Adrego, Gerrit Freund, Andreas Kroh, Andrea Schenk, Justus P Beier, Anja M Boos
{"title":"Lipedema and obesity: biological interactions, diagnostic challenges, and principles of interdisciplinary management - a narrative review.","authors":"Deborah Scherkamp, Victoria Wachenfeld-Teschner, Larissa Rabe, Fábio Dos Santos Adrego, Gerrit Freund, Andreas Kroh, Andrea Schenk, Justus P Beier, Anja M Boos","doi":"10.1080/21623945.2026.2719267","DOIUrl":"10.1080/21623945.2026.2719267","url":null,"abstract":"<p><p>Lipedema and obesity are chronic, frequently progressive disorders that can present with increased adipose-tissue volume, functional impairment and reduced quality of life. Although often approached as differential diagnoses, they frequently coexist and may aggravate one another. This narrative review addresses how lipedema and obesity interact biologically and clinically and what evidence supports a staged interdisciplinary approach to diagnosis and management. Obesity is increasingly conceptualized as an adiposity-based chronic disease characterized by excess adipose, abnormal adipose-tissue distribution or dysfunction, and associated medical or functional impairment. Obesity can impair lymphatic morphology and function, whereas lymphatic dysfunction may promote subcutaneous adipose-tissue expansion and fibrosis. Literature was identified through iterative PubMed searches and focused supplementary searches in Embase and the Cochrane Library. Publications were selected purposively for their relevance to predefined clinical and mechanistic domains; no systematic screening or formal risk-of-bias assessment was performed. This review synthesizes clinical overlap, biological evidence, diagnostic implications, and staged management for predominantly adult women with suspected or confirmed lipedema, including those with coexisting overweight or obesity. The proposed framework is intended to support clinical reasoning rather than serve as a formal guideline.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2719267"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of select 3D human mesenchymal stromal cell-derived spheroid models for adipogenic differentiation.","authors":"Bianca Vezzani, Elisa Tamburini, Anna Terenziani, Nadia Ilaria Oliverio, Simonetta Croci, Alessandro Bartolomucci","doi":"10.1080/21623945.2026.2736340","DOIUrl":"10.1080/21623945.2026.2736340","url":null,"abstract":"<p><p><i>In vitro</i> modelling of adipose tissue (AT) commonly employs 2D systems, which do not fully capture the complexity of AT, lacking cell-cell interactions and extracellular matrix (ECM) remodelling. Despite the innovations in 3D culture systems offering physiologically relevant AT platforms, the field lacks consensus and cross-protocol method comparison. We performed a comparative analysis of three scaffold-free spheroid-generation techniques: Ultra Low Attachment plates (ULA), Hanging Drops (HD), and Microwell Culture Plates (MCP), utilizing human AT-derived mesenchymal stromal cells. Each method produced viable spheroids of similar size and morphology within 48 hours. However, MCP demonstrated greater uniformity and a significant increase in mass density when compared to ULA and HD. Adipogenic media increased spheroid size in ULA and MCP, but not in HD spheroids. Notably, the diameter of ULA spheroids was 2- and 6-times larger compared to HD and MCP ones, respectively, regardless of adipogenic induction. Gene expression analysis indicated that all techniques led to <i>PPARγ</i> and <i>ADIPOQ</i> expression during adipogenesis. All methods supported adipocyte differentiation, as evidenced by lipid droplet accumulation, PLIN1, CD36, and HSL expression, and ECM rearrangement. These findings suggest that all the described techniques constitute a robust platform for producing adipogenesis-competent spheroids, while method-specific differences suggest an application-dependent choice.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2736340"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-01Epub Date: 2026-01-18DOI: 10.1080/21623945.2025.2610544
Seyede Fatemeh Heydari, Mehrdad Moosazadeh Moghaddam, Soyar Sari, Mohammad Heiat
{"title":"Physical differentiation of adipose-derived mesenchymal stem cells into pancreatic beta-like cells using cell-imprinting and evaluation of insulin production.","authors":"Seyede Fatemeh Heydari, Mehrdad Moosazadeh Moghaddam, Soyar Sari, Mohammad Heiat","doi":"10.1080/21623945.2025.2610544","DOIUrl":"10.1080/21623945.2025.2610544","url":null,"abstract":"<p><p>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 <i>PDX1, NKX6.1, NGN3,</i> and <i>insulin</i>. The results of dithizone staining and ELISA confirmed insulin secretion by differentiated cells compared to stem cells (<i>p</i> ≤ 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 (<i>p</i> ≤ 0.05).</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2610544"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-01Epub Date: 2026-03-13DOI: 10.1080/21623945.2026.2638071
Sen Li, Shuhui Ji, Zihan Yu, Haiyang Liu, Jianxin Wu
{"title":"Super-enhancer-associated miR-1260b coordinates adipogenesis and metabolic programming in human adipose stem cells.","authors":"Sen Li, Shuhui Ji, Zihan Yu, Haiyang Liu, Jianxin Wu","doi":"10.1080/21623945.2026.2638071","DOIUrl":"10.1080/21623945.2026.2638071","url":null,"abstract":"<p><p>Obesity and its metabolic complications represent a major and growing public health burden, for which effective therapeutic strategies remain limited. Although super-enhancers are recognized as key regulators of cell identity and adipogenesis, the roles of super-enhancer- microRNAs in obesity and adipocyte dysfunction remain insufficiently characterized. Here, we identify miR-1260b as a super-enhancer-associated miRNA that influences human adipogenesis. Analysis of adipose-related datasets from SEdb 2.0 revealed that MIR1260B is consistently linked to a clustered SE region across multiple human adipose tissues. Integrated ATAC-seq and Hi-C analyses demonstrated progressive chromatin opening and dynamic enhancer-promoter interactions between this SE and the MIR1260B promoter during adipogenic differentiation. Functionally, miR-1260b overexpression markedly inhibited adipocyte differentiation of human adipose-derived stem cells. Quantitative proteomic profiling revealed that miR-1260b suppresses adipogenic and lipogenic programmes while activating lipid catabolic pathways. Notably, the MIR1260B-associated SE overlaps with a previously reported diabetes-associated SNP, and external clinical datasets indicate reduced miR-1260b levels in umbilical cord serum from children at increased risk of obesity. Together, these findings suggest that miR-1260b may function as a super-enhancer-associated regulator that inhibits adipogenesis and indicate that SE-informed multi-omics approaches can aid in identifying miRNA regulators relevant to metabolic disorders of obesity.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2638071"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-01Epub Date: 2026-10-06DOI: 10.1080/21623945.2026.2719272
Tingting Lai, Yi Lin, Fuping Ding, Zhenni Shi, Jun Zhang, Yongjin Yan, Shunzhong Gu, Kunting Zhong, Jinhong Liu, Weiyu Liang, Yilin Duan, Zhanhui Huang, Shuhe Zhang, Jin Zhang
{"title":"Cinnamaldehyde combined with 18β-glycyrrhetinic acid promotes the differentiation of C3H10T1/2 MSCs into thermogenic adipocytes through PGC1α/FNDC5/UCP1 pathway.","authors":"Tingting Lai, Yi Lin, Fuping Ding, Zhenni Shi, Jun Zhang, Yongjin Yan, Shunzhong Gu, Kunting Zhong, Jinhong Liu, Weiyu Liang, Yilin Duan, Zhanhui Huang, Shuhe Zhang, Jin Zhang","doi":"10.1080/21623945.2026.2719272","DOIUrl":"10.1080/21623945.2026.2719272","url":null,"abstract":"<p><p>Finding bioactive substances that can promote the <i>de novo differentiation</i> of stem cells into thermogenic adipocytes is a promising anti-obesity strategy. Cinnamaldehyde (CM) and 18β-glycyrrhetinic acid (GA) are the main active ingredients in Chinese herbal medicine. In this study, C3H10T1/2 mesenchymal stem cells (MSCs) were used to investigate whether CM and GA could promote the differentiation of MSCs into thermogenic adipocytes and the possible molecular mechanism. The experimental results demonstrated that CM and GA could promote the mRNA expression of adipogenic transcription factors <i>Pparγ, Cebpα</i> and <i>Cebpβ</i>, as well as thermogenic adipocyte-specific markers <i>Pgc1α</i> and <i>Ucp1</i>. CM combined with GA further enhanced these effects. CM/GA alone or in combination could increase the expression of FNDC5 mRNA and protein. After transfection with FNDC5 siRNA, the mRNA and protein levels of FNDC5 and UCP1 were significantly decreased, while the levels of PGC1α did not change apparently. After the combination of CM and GA intervention, the levels of FNDC5 and UCP1 were slightly restored, but could not return to the normal level. In conclusion, CM and GA could promote the differentiation of C3H10T1/2 MSCs into thermogenic adipocytes, and their combination could enhance this effect, which may be mediated by PGC1α/FNDC5/UCP1 signalling pathway.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2719272"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypotonic induced volume activated chloride current in 3T3-L1 preadipocytes and its effect on cell differentiation.","authors":"Hua Guan, Zhenghao Huang, Ziyue Wang, Aoqi Xiang, Lusha Zhang, Xiaochang Chen, Peihong Su, Rui Wang, Haifeng Zhang, Qi Yu","doi":"10.1080/21623945.2026.2649662","DOIUrl":"10.1080/21623945.2026.2649662","url":null,"abstract":"<p><p>Volume-activated chloride current (VACC), the most common and abundant anion current in organisms, is involved in various physiological and pathological processes. However, its expression and characteristics in preadipocytes remain unclear. Whole-cell patch clamp technique was used to investigate the presence and properties of VACC in 3T3-L1 preadipocytes, as well as the effects of chloride channel blockers (NPPB, DIDS, and tamoxifen) on this current under different osmotic conditions. Additionally, 3T3-L1 preadipocytes were treated with the chloride channel blocker TMEM16A to observe its effect on cell differentiation. Hypotonic stimulation significantly induced whole-cell currents in 3T3-L1 preadipocytes, which exhibited obviously outward-rectifying and volume-activated characteristics. Under hypotonic stimulation, NPPB, DIDS, and tamoxifen all inhibited the current, with NPPB showing a significantly stronger inhibitory effect than DIDS and tamoxifen. Moreover, growth-arrested 3T3-L1 preadipocytes at 2 days post-confluence were successfully induced, with mRNA levels of C/EBPα, C/EBPβ, PPARγ and FABP4 peaking on day 3 and decreasing by day 14. Protein levels of PPARγ, perilipin 1 and LRRC8A were significantly upregulated during differentiation. Treatment with TMEM16A significantly reduced adipocyte lipid droplet formation and FABP4 mRNA/protein levels, but increased C/EBPα and PPARγ mRNA levels, as well as LRRC8A protein levels after 3 days. Collectively, our results clarify the characteristics of VACC in 3T3-L1 preadipocytes, confirm the inhibitory effect of chloride channel blockers on 3T3-L1 preadipocyte differentiation, fill the gap in the understanding of VACC in preadipocytes, and lay a preliminary experimental foundation for further exploring the role of VACC in adipocyte differentiation.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2649662"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-01Epub Date: 2026-06-24DOI: 10.1080/21623945.2026.2694149
Chen Kai, Haiyan Xu, Suzhen Lv, Xin Huang
{"title":"Twf1 regulates adipocyte proliferation and differentiation through Yap nucleus accumulation.","authors":"Chen Kai, Haiyan Xu, Suzhen Lv, Xin Huang","doi":"10.1080/21623945.2026.2694149","DOIUrl":"10.1080/21623945.2026.2694149","url":null,"abstract":"<p><p>Obesity involves white adipose tissue (WAT) expansion via hyperplasia and hypertrophy. Impaired adipocyte proliferation leads to pathological hypertrophy, inflammation and metabolic dysfunction. Aberrant F‑actin turnover disrupts proliferation/differentiation. Twinfilin‑1 (Twf1) regulates actin dynamics and cell proliferation/differentiation, but its role in adipocytes is unknown. Obese mice were induced by high‑fat diet (HFD) and weight loss by calorie restriction. Inguinal, epididymal and scapular adipose tissues were collected. Proteomics used pressure cycling, DDA library building and DIA quantification. Twf1 expression was validated by RT‑qPCR and Western blot. In C3H10T1/2 preadipocytes, Twf1 knockdown and overexpression were established. Differentiation was induced with dexamethasone, rosiglitazone, insulin and IBMX. Adipogenesis and proliferation were assessed by RT‑qPCR, Western blot, Oil Red O and CCK8. Nuclear‑cytoplasmic fractionation evaluated Yap localization and HIPPO activity. HFD mice showed weight gain, dyslipidemia and adipocyte hypertrophy, reversed by weight loss. Proteomics identified 43 proteins intersecting obesity, weight loss, and actin‑related datasets; Twf1 was upregulated in obese epididymal/inguinal fat and downregulated after weight loss. In C3H10T1/2 cells, Twf1 knockdown enhanced white adipocyte differentiation (upregulated Pparg2, Fsp27, Fabp4) and proliferation (2.28‑fold vs. control), promoted Yap nuclear accumulation, and inhibited HIPPO signalling. Twf1 overexpression reduced differentiation, lipid droplets, and proliferation (to 44.7% of control). Twf1 is upregulated in white/beige adipose tissue of obese mice and downregulated after weight loss. Twf1 knockdown promotes Yap nuclear accumulation, inhibits HIPPO and enhances adipocyte proliferation and white adipocyte maturation, indicating a key role in obesity development.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2694149"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AdipocytePub Date : 2026-12-01Epub Date: 2026-04-29DOI: 10.1080/21623945.2026.2665903
Weihua Xiao, Jingdan Sheng, Chunjiao Liu, Junqiang Li, Peng Shu, Maofen Jiang, Min Wang, Ji He, Haifen Ma, Yaxin Ding
{"title":"mTORC2 regulates lipid metabolism-driven TAMs via the PPAR-γ/CD36 pathway to promote liposarcoma progression.","authors":"Weihua Xiao, Jingdan Sheng, Chunjiao Liu, Junqiang Li, Peng Shu, Maofen Jiang, Min Wang, Ji He, Haifen Ma, Yaxin Ding","doi":"10.1080/21623945.2026.2665903","DOIUrl":"10.1080/21623945.2026.2665903","url":null,"abstract":"<p><p>Tumour-associated macrophages (TAMs) exert a pivotal function in tumour progression, and M2-type TAMs are closely linked to tumour-promoting functions. Mechanistic target of rapamycin complex 2 (mTORC2) may mediate TAM polarization and subsequent tumour development, yet their roles in liposarcoma (LPS) remain unclear. Macrophage polarization was assessed via flow cytometry for CD206. Western blot for Arg-1, Rictor, PPAR-γ, CD36, ACSL1 and CPT2, qPCR for IL-10, Arg-1 and Ym1, and ELISA for IL-10 secretion. Fatty acid metabolism was evaluated using free fatty acid (FFA) uptake assays and Oil Red O staining for intracellular lipid droplets. A Transwell assay was established to assess the effect of treated macrophages on LPS cell biology, and EdU assays were used for proliferation assessment. Transwell migration and invasion assays were utilized for assessing cellular motility. IL-4 induced RAW264.7 macrophages to undergo M2 polarization, characterized by upregulated CD206, Arg-1, and IL-10. During this process, mTORC2 was activated, promoting FFA uptake, lipid droplet accumulation, and fatty acid oxidation via the PPAR-γ/CD36 axis. Co-culture experiments showed that IL-4-polarized M2 macrophages enhanced LPS cell proliferation, migration, and invasion; these effects were inhibited by JR-AB2-011 and restored by LPA, confirming mTORC2-PPAR-γ/CD36-mediated TAMs drive LPS progression. mTORC2 regulates M2 TAM polarization and metabolic reprogramming via the PPAR-γ/CD36 pathway, thereby promoting LPS cell proliferation, migration, and invasion.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"15 1","pages":"2665903"},"PeriodicalIF":3.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}