{"title":"Adipogenic dedifferentiation enhances survival of human umbilical cord-derived mesenchymal stem cells under oxidative stress.","authors":"Yin Yuan, Meina Kuang, Tengye Yu, Sirui Huang, Fujie Jiang, Biyi Lu, Mingen Cai, Xin Lu","doi":"10.1080/21623945.2025.2467150","DOIUrl":"10.1080/21623945.2025.2467150","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2467150"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456410","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 : 2025-12-01Epub Date: 2025-04-10DOI: 10.1080/21623945.2025.2489467
Mansour M Alotaibi, Naif Z Alrashdi, Marzouq K Almutairi Pt, Mohammed M Alqahtani, Anwar B Almutairi, Sami M Alqahtani, Hamoud M Alajel, Amani K Bajunayd
{"title":"Association of adipose tissue infiltration with cardiac function: scoping review.","authors":"Mansour M Alotaibi, Naif Z Alrashdi, Marzouq K Almutairi Pt, Mohammed M Alqahtani, Anwar B Almutairi, Sami M Alqahtani, Hamoud M Alajel, Amani K Bajunayd","doi":"10.1080/21623945.2025.2489467","DOIUrl":"https://doi.org/10.1080/21623945.2025.2489467","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2489467"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965655","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 : 2025-12-01Epub Date: 2025-05-26DOI: 10.1080/21623945.2025.2508188
Hernan Yupanqui-Lozno, Jancy Andrea Huertas-Quintero, Maria E Yupanqui-Velazco, Rocío A Salinas-Osornio, Carlos M Restrepo, Adriana Gonzalez, Edna J Nava-Gonzalez, Luis G Celis-Regalado, Constanza Neri Morales, Victor M Hernandez-Escalante, Julio Licinio, Hugo A Laviada-Molina, Ernesto Rodriguez-Ayala, Carlos Arango, Raul A Bastarrachea
{"title":"One-year metreleptin in Colombian sisters with congenital leptin deficiency.","authors":"Hernan Yupanqui-Lozno, Jancy Andrea Huertas-Quintero, Maria E Yupanqui-Velazco, Rocío A Salinas-Osornio, Carlos M Restrepo, Adriana Gonzalez, Edna J Nava-Gonzalez, Luis G Celis-Regalado, Constanza Neri Morales, Victor M Hernandez-Escalante, Julio Licinio, Hugo A Laviada-Molina, Ernesto Rodriguez-Ayala, Carlos Arango, Raul A Bastarrachea","doi":"10.1080/21623945.2025.2508188","DOIUrl":"10.1080/21623945.2025.2508188","url":null,"abstract":"<p><p>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/m<sup>2</sup> (OBX1, age 27) and 60 to 48 kg/m<sup>2</sup> (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.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2508188"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141245","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":"Bioactive peptides PDBSN improve mitochondrial function and suppression the oxidative stress in human adiposity cells.","authors":"Huiping Shen, Yong Lei, Wen Xie, Tieliang Ma, Li Bao, Qin Gao, Bingyu Chen, Biao Dai, Dani Qin","doi":"10.1080/21623945.2023.2278213","DOIUrl":"10.1080/21623945.2023.2278213","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":" ","pages":"2278213"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520168","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":"Anti-inflammatory effect of Angiotensin 1-7 in white adipose tissue.","authors":"Nozomi Nishida, Satoru Sugimoto, Satoshi Miyagaki, Chiharu Cho, Madoka Konishi, Takeshi Goda, Mihoko Yamaguchi, Yasuhiro Kawabe, Hidechika Morimoto, Joji Kusuyama, Takuro Okamura, Masahide Hamaguchi, Jun Mori, Hisakazu Nakajima, Michiaki Fukui, Tomoko Iehara","doi":"10.1080/21623945.2024.2449027","DOIUrl":"10.1080/21623945.2024.2449027","url":null,"abstract":"<p><p>Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are <i>in vitro</i> experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2449027"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969170","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 : 2025-12-01Epub Date: 2025-06-05DOI: 10.1080/21623945.2023.2283213
Morgane Couchet, Hui Gao, Felix Klingelhuber, Jutta Jalkanen, Thais De Castro Barbosa, Muhmmad Omar-Hmeadi, Lucas Massier, Natalie Krahmer, Niklas Mejhert, Mikael Rydén
{"title":"Adipogenic characterization of immortalized CD55<sup>+</sup> progenitor cells from human white adipose tissue.","authors":"Morgane Couchet, Hui Gao, Felix Klingelhuber, Jutta Jalkanen, Thais De Castro Barbosa, Muhmmad Omar-Hmeadi, Lucas Massier, Natalie Krahmer, Niklas Mejhert, Mikael Rydén","doi":"10.1080/21623945.2023.2283213","DOIUrl":"10.1080/21623945.2023.2283213","url":null,"abstract":"<p><strong>Background: </strong>Mature adipocytes are difficult to study ex vivo, prompting the use of human adipose progenitor cells (hAPCs). However, hAPCs undergo replicative senescence, limiting their utility in long-term studies.</p><p><strong>Methods: </strong>We inserted human telomerase reverse transcriptase (TERT) into the AAVS1 locus of CD55+ hAPCs derived from abdominal subcutaneous adipose tissue, and characterized the cells before and after adipogenic differentiation.</p><p><strong>Results: </strong>TERT-hAPCs retained proliferative and adipogenic capacities for over 80 passages, comparable to early-passage wild type hAPCs. Transcriptomic and proteomic analyses confirmed strong adipocyte gene expression. Functionally, TERT-hAPCs responded to insulin and lipolytic stimuli (isoprenaline, dibutyryl cAMP, TNF-α). They adapted well to both 2D and 3D cultures, with improved adipogenesis under spheroid conditions.</p><p><strong>Conclusion: </strong>Immortalization of CD55+ hAPCs yields cells with stable proliferative and adipogenic capacity across passages. Being cryopreservable and suitable for both 2D and 3D cultures, TERT-hAPCs offer a reliable, reusable model system for adipocyte studies using cells with a consistent genetic background.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":" ","pages":"2283213"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138045962","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 : 2025-12-01Epub Date: 2025-06-30DOI: 10.1080/21623945.2025.2524638
Mengjiang Lu, Ziwei Yu, Xingyu Yang, Ze Yang, Tiancheng Xu, Zhi Yu, Xinyue Jing, Li An, Jianbin Zhang, Bin Xu
{"title":"Electroacupuncture stimulation induced M1/M2 polarization in white adipose tissues by activating the Y1 receptor in obese mice to reduce chronic inflammation.","authors":"Mengjiang Lu, Ziwei Yu, Xingyu Yang, Ze Yang, Tiancheng Xu, Zhi Yu, Xinyue Jing, Li An, Jianbin Zhang, Bin Xu","doi":"10.1080/21623945.2025.2524638","DOIUrl":"10.1080/21623945.2025.2524638","url":null,"abstract":"<p><p>Chronic inflammation in obesity can induce complications such as diabetes and cardiovascular disease. Visceral adipose tissue is the main source of inflammation, but it is difficult to regulate effectively. Here, we investigated whether ES suppressed inflammation in eWAT and reduced chronic inflammation in obese individuals. We established a high-fat diet (HFD) model with C57BL/6J mice to measure chronic inflammation in obesity. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, the immunostaining and flow cytometry were used to detect the Y1 receptors in macrophage. Finally, the key role of the M1/M2 polarization in white adipose tissues by activating the Y1 receptor was verified by Y1 receptor antagonist BIBP3226. ES reduced the contents of IL-1β, TNF-α, IL-6 and TGF-β in the plasma and the mRNA expression of il-1 and tnfα in eWAT. Also, ES suppressed SNA in eWAT which regulated NPY1R receptor. In addition, ES induced M1/M2 polarization in eWAT via the Y1 receptor. The injection of a Y1 receptor (NPY1R) antagonist BIBP3226 restrained M1/M2 polarization. Further studies revealed that ES regulated sympathetic axons in eWAT to activate the Y1 receptor. This research demonstrates ES reduce chronic inflammation e mechanism is associated with the sympathetic Y1 receptor pathway, which promotes M1/M2 polarization.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2524638"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525976","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 : 2025-12-01Epub Date: 2025-04-29DOI: 10.1080/21623945.2025.2490258
Shiyue Sun, Muhammad Arif Aslam, Eun Bi Ma, Gahui Lee, Hafiz Muhammad Ahmad Javaid, Somy Yoon, Joo Young Huh
{"title":"Activation of CXCR7 exerts an inhibitory effect on adipogenesis through regulation of β-arrestin2/Wnt and AKT signalling.","authors":"Shiyue Sun, Muhammad Arif Aslam, Eun Bi Ma, Gahui Lee, Hafiz Muhammad Ahmad Javaid, Somy Yoon, Joo Young Huh","doi":"10.1080/21623945.2025.2490258","DOIUrl":"https://doi.org/10.1080/21623945.2025.2490258","url":null,"abstract":"<p><p>CXCR7, an alternative receptor for the inflammatory chemokine SDF-1, is involved in cell proliferation and migration. Recent studies have reported that CXCR7 also plays a role in adipose tissue. However, evidence regarding the role of CXCR7 and its ligands in adipocyte differentiation is limited. In this study, we aimed to elucidate changes in CXCR7 expression during adipocyte differentiation and the role of the SDF-1/CXCR7/CXCR4 axis in adipogenesis using recombinant SDF-1, the CXCR7 ligand CCX771, and small interfering RNAs. The results indicated that the levels of SDF-1 and its receptors, CXCR7 and CXCR4, decreased during the early stages of adipogenesis. Treatment with recombinant SDF-1 and CCX771 inhibited adipogenesis and lipid accumulation by inducing β-arrestin2, Wnt expression, and AKT phosphorylation and downregulating C/EBPα, PPARγ, and FABP4 expression. In contrast, knockdown of SDF-1 and CXCR7 in preadipocytes downregulated the β-arrestin2/Wnt and AKT pathway, leading to the induction of adipogenesis. Meanwhile, knockdown of CXCR4 had no significant effect. In mice, basal gene expression levels of SDF-1 and CXCR7 were higher in the stromal vascular fraction compared to mature adipocytes and were significantly upregulated by a high-fat diet. Our results provide new insights into the local role of the SDF-1-CXCR7 axis in adipocytes and offer additional benefits for the prevention of obesity-related metabolic disorders.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2490258"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958040","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 : 2025-12-01Epub Date: 2025-06-21DOI: 10.1080/21623945.2025.2518285
Lisa Guerrier, Ruddy Richard, Jean Brac de la Perrière, Ophélie Bacoeur-Ouzillou, Julianne Touron, Johan Gagnière, Alexandre Pinel, Corinne Malpuech-Brugère
{"title":"FLOT chemotherapy treatment affects adipocyte's lipid metabolism: an <i>in vitro</i> study.","authors":"Lisa Guerrier, Ruddy Richard, Jean Brac de la Perrière, Ophélie Bacoeur-Ouzillou, Julianne Touron, Johan Gagnière, Alexandre Pinel, Corinne Malpuech-Brugère","doi":"10.1080/21623945.2025.2518285","DOIUrl":"10.1080/21623945.2025.2518285","url":null,"abstract":"<p><p>Cachexia is a complex syndrome that is often associated with cancer. Chemotherapy, one of the main cancer treatments, worsens weight loss in cancer-induced cachexia. In this context, it is thought that fat loss precedes muscle loss, and that alterations in adipose tissue are associated with tumours. However, the effect of cancer treatment on adipose tissue is not well understood. This study aimed to evaluate the impact of chemotherapy alone on mature 3T3-L1 adipocytes to identify the mechanisms contributing to adipose tissue alteration. The murine cell line 3T3-L1, a model of mature adipocytes, was used in this study. After differentiation, cells were treated for 48 h with a chemotherapy cocktail called FLOT composed of 5-fluorouracil, leucovorin, oxaliplatin and docetaxel at two concentrations (FLOT 1X and 0.1X). The control group was treated with the vehicle of the chemotherapy cocktail. Viability, mitochondrial function and dynamics, lipid metabolism, and cellular stress were also evaluated. FLOT 1X chemotherapy significantly reduced viability of mature 3T3-L1 cells and inhibited lipid accumulation. Interestingly, while FLOT 1X treatment downregulated lipogenesis markers, FLOT 0.1X treatment upregulated some of them. Although, the treatment showed no effect on mitochondrial respiration or density, it significantly increased expression of oxidative stress and inflammation markers in adipocytes.This <i>in vitro</i> study provides the first evidence of FLOT chemotherapy's direct effects on healthy mature adipocytes. The results demonstrate significant treatment-induced reductions in cell viability along with dysregulation of both lipogenic and lipolytic pathways. These findings elucidate previously unrecognized mechanisms underlying adipose tissue dysfunction in cancer cachexia.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2518285"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339800","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 : 2025-12-01Epub Date: 2025-02-17DOI: 10.1080/21623945.2025.2468275
Lea M Merz, Karsten Winter, Sandy Richter, Sonja Kallendrusch, Andreas Horn, Sonja Grunewald, Nora Klöting, Kerstin Krause, Wieland Kiess, Diana Le Duc, Antje Garten
{"title":"Effects of alpelisib treatment on murine <i>Pten</i>-deficient lipomas.","authors":"Lea M Merz, Karsten Winter, Sandy Richter, Sonja Kallendrusch, Andreas Horn, Sonja Grunewald, Nora Klöting, Kerstin Krause, Wieland Kiess, Diana Le Duc, Antje Garten","doi":"10.1080/21623945.2025.2468275","DOIUrl":"10.1080/21623945.2025.2468275","url":null,"abstract":"<p><p> Phosphatase and tensin homolog (PTEN) hamartoma tumour syndrome (PHTS) is a rare disorder caused by germline mutations in the tumour suppressor gene PTEN, a key negative regulator of phosphatidylinositol 3-kinase (PI3K)/AKT signalling. Children with PHTS often develop lipomas, for which only surgical resection is available as treatment. We investigated the effects of the selective PI3K-inhibitor alpelisib on Pten-deficient lipomas. After incubation with alpelisib or the non-selective PI3K inhibitor wortmannin, we analysed histology, gene expression, and Pi3k pathway in lipoma and control epididymal adipose tissue (epiWAT). Alpelisib increased adipocyte area in lipomas compared to epiWAT. Baseline gene expression showed higher levels of markers for proliferation (<i>Pcna</i>), fibrosis (<i>Tgfb1</i>), and adipogenesis (<i>Pparg</i>) in lipomas, while hormone-sensitive lipase expression was lower than in epiWAT. Following alpelisib incubation, target genes of Pi3k signalling and extracellular matrix factors were reduced. We confirmed Pi3k inhibition through detecting decreased Akt levels compared to control treatment. Human lipoma samples treated with alpelisib showed variable lipolysis responses, suggesting variability in therapeutic outcomes. We established an ex vivo model to study alpelisib effects on Pten-deficient lipomas. These results underscore the therapeutic potential of targeted PI3K inhibition in the treatment of PHTS-associated lipomas, particularly in cases that are inoperable.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2468275"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439506","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}