The FASEB Journal最新文献

{"title":"PTPN9 promotes melanoma progression by regulating the ferroptosis pathway","authors":"Hongmei Wang,&nbsp;Sen Qiao,&nbsp;Lingyan Huang,&nbsp;Zhengping Zhang,&nbsp;Jiao Wang,&nbsp;Wenxiu Tian","doi":"10.1096/fj.202402285R","DOIUrl":"https://doi.org/10.1096/fj.202402285R","url":null,"abstract":"<p>In recent years, there has been a gradual increase in the incidence and mortality rates of melanoma, posing a significant threat to human health and life. Protein tyrosine phosphatases (PTPNs) have been implicated in the progression of various human cancers, including breast, lung, and cervical cancer. To investigate PTPN9 expression in melanoma, impacting the disease's survival and prognosis. Our study, which involved an analysis of The Cancer Genome Atlas database and immunohistochemical staining of pathological sections, identified an upregulation of PTPN9 expression in melanoma, impacting the disease's survival and prognosis. At the cellular level, we investigated the effects of PTPN9 on the proliferation, invasion, and metastasis of A375 and SK-MEL-28 cells. Through various experimental techniques such as Western blot protein detection, electron microscopy, and oil red O staining, we observed that PTPN9 potentially contributes to the development of skin cutaneous melanoma (SKCM) by regulating ferroptosis-related proteins ACSL4, FTH1, and P53, thereby influencing lipid metabolism. The results of this study highlight the unique role of PTPN9 in SKCM and suggest its potential as a biomarker for the disease.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 4","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary intake of whale oil–containing ω-3 long-chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice","authors":"Ryoji Yanai,&nbsp;Genta Yasunaga,&nbsp;Shunya Tsuji,&nbsp;Takeshi Honda,&nbsp;Arihiro Iwata,&nbsp;Eiji Miyagawa,&nbsp;Koji Yoshida,&nbsp;Mitsuhiro Kishimoto,&nbsp;Hiroki Sakai,&nbsp;Yoshihiro Fujise,&nbsp;Masataka Asagiri,&nbsp;Yoshinori Mitamura","doi":"10.1096/fj.202402041R","DOIUrl":"https://doi.org/10.1096/fj.202402041R","url":null,"abstract":"<p>Age-related macular degeneration (AMD) is a leading cause of blindness in Western and developing countries. Since antivascular endothelial growth factor (VEGF) therapy is available for the regression of choroidal neovascularization (CNV), it does not work for the pathophysiology of AMD so a cure is increasingly demanded. Whale oil promotes various bodily functions, such as anti-inflammatory effects for cardiovascular disease, but its physiological mechanisms are still unclarified. Here, we examined the effects of whale oil on a mouse model of AMD. The area of CNV measured in choroidal flat-mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice free of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). The plasma concentrations of ω-3 LCPUFAs were higher, whereas those of ω-6 LCPUFAs were lower in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of VEGF was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil–containing ω-3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and it, therefore, warrants further study as a means to protect against AMD in humans.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 4","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402041R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMBIM1 ameliorates sepsis-induced cardiac dysfunction by promoting Parkin-mediated mitophagy","authors":"Weichang Huang,&nbsp;Anni Lou,&nbsp;Jun Wang,&nbsp;Yuegang Wang,&nbsp;Wenyong Zhang,&nbsp;Jierui Li,&nbsp;Shuanghu Wang,&nbsp;Shiyu Geng,&nbsp;Guozhen Wang,&nbsp;Xu Li","doi":"10.1096/fj.202402599RR","DOIUrl":"https://doi.org/10.1096/fj.202402599RR","url":null,"abstract":"<p>Myocardial dysfunction is a significant complication of sepsis that is associated with elevated mortality rates. Transmembrane BAX inhibitor motif containing 1 (TMBIM1), a stress-responsive protein, has garnered interest in the field of cardiovascular disease for its cardioprotective properties. Nevertheless, the role of TMBIM1 on sepsis-induced cardiac dysfunction (SICD) remains unknown. Here, our findings revealed a significant elevation in TMBIM1 expression within the myocardium following endotoxin challenge and further demonstrate the cardioprotective effects of TMBIM1 through adenovirus-mediated gene manipulation. Notably, lipopolysaccharide exposure markedly induced mitochondrial dysfunction in cardiomyocytes, which was effectively alleviated by TMBIM1 overexpression, while TMBIM1 knockdown exacerbated this dysfunction. Moreover, in cardiomyocytes subjected to endotoxin challenge, TMBIM1 was observed to interact with Parkin, facilitating its translocation from the cytosol to damaged mitochondria. This interaction enhanced the activation of mitophagy, thereby promoting the clearance of dysfunctional mitochondria and subsequently mitigating cellular injury. Hence, targeting TMBIM1 could be a novel therapeutic strategy for treating SICD.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 4","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-body vibration protects against chronic high-altitude hypoxic bone loss by regulating the nitric oxide/HIF-1α axis in osteoblasts","authors":"Dan Wang,&nbsp;Ruobing Liu,&nbsp;Yuanjun Ding,&nbsp;Qilin Pei,&nbsp;Tao Sun,&nbsp;Xi Shao,&nbsp;Maogang Jiang,&nbsp;Juan Liu,&nbsp;Jinghui Huang,&nbsp;Zedong Yan,&nbsp;Xiaoxia Hao,&nbsp;Da Jing,&nbsp;Jing Cai","doi":"10.1096/fj.202402629R","DOIUrl":"https://doi.org/10.1096/fj.202402629R","url":null,"abstract":"<p>The hypobaric hypoxia environment found at high altitudes imposes various reversible and irreversible detrimental effects on living organisms. Accumulating evidence suggests that hypobaric hypoxia negatively impacts skeleton health by diminishing bone quality and disrupting bone microarchitecture. However, therapeutic strategies to counteract this bone loss remain limited. This study investigates the impact of whole-body vibration (WBV) stimulation on skeletal health of rats continuously exposed to simulated hypobaric hypoxia environment at an altitude of 4500 m for 6 weeks. We found that WBV stimulation at 30 Hz and 0.3 g significantly improved femoral bone mass, microarchitecture, and biomechanical properties in rats exposed to chronic hypobaric hypoxia. Additionally, in vitro studies demonstrated that WBV enhanced osteogenic potential and activity in primary osteoblasts under hypoxia conditions. It also reduced levels of hypoxia-inducible factor 1α (HIF-1α), a key transcription factor involved in cellular response to hypoxia. Conversely, overexpression of HIF-1α significantly inhibited cellular differentiation and osteogenesis in osteoblasts exposed to WBV stimulation under hypoxic conditions. Furthermore, WBV stimulation led to a significant increase in nitric oxide (NO) concentrations in osteoblasts during hypoxic exposure. In vitro experiments showed that blocking of NO synthesis with L-NAME impeded WBV-stimulated osteogenic activity in hypoxia-exposed osteoblasts. In vivo studies demonstrated that inhibiting NO synthesis similarly abolished the positive impact of WBV on bone microarchitecture and biomechanical properties under hypobaric hypoxia. Collectivity, our findings indicate that WBV protects against hypobaric hypoxia-induced bone loss by regulating the NO/HIF-1α axis in osteoblasts, and reveal its clinical potential as a promising non-invasive approach.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated fatty acid metabolism in pericardiac adipose tissue of pulmonary hypertension due to left heart disease mice","authors":"Haihua Qiu,&nbsp;Jingyuan Chen,&nbsp;Zhang Mei,&nbsp;Wenjie Chen,&nbsp;Luo Jun,&nbsp;Yusi Chen,&nbsp;Yingjie Tan,&nbsp;Tianyu Wang,&nbsp;Yaqin Chen,&nbsp;Jiang Li","doi":"10.1096/fj.202402842R","DOIUrl":"https://doi.org/10.1096/fj.202402842R","url":null,"abstract":"<p>Pulmonary hypertension associated with left heart disease (PH-LHD) represents the most prevalent form of pulmonary hypertension; however, being lacks precise and effective treatment strategies. Recent clinical studies have indicated a positive correlation between the volume of pericardiac adipose tissue (PAT) and the severity of PH-LHD. Nonetheless, there is a paucity of research characterizing PAT phenotypes in PH-LHD disease models. This study aimed to elucidate the gene-level characteristics of PAT in PH-LHD through RNA sequencing and targeted metabolomic analysis of PAT in order to identify potential therapeutic targets for PH-LHD by modulating PAT. This study developed a mouse model of PH-LHD through cardiac overload combined with metabolic syndrome and verified that PAT volume and adipocyte size were significantly increased in PH-LHD mice. We used RNA sequencing to reveal that DEGs in PAT were primarily enriched in fatty acid metabolism pathways. Then, real-time PCR showed no significant differences in the mRNA expression of inflammatory markers or adipocytokines; however, genes of fatty acid synthesis (Fasn, Acaca, and Scd1) and fatty acid decomposition (Ehhadh, Acot4, and Pdk1) significantly changed between the two groups. Consistently, targeted metabolomic analysis showed levels of most types of medium- and long-chain fatty acids substantially reduced in PAT, suggesting that PAT in PH-LHD mice exhibits suppressed fatty acid de novo synthesis and enhanced fatty acid breakdown, resulting in impaired fatty acid storage. These findings highlight the potential of targeting PAT fatty acid synthesis and metabolism pathways as a novel therapeutic approach for PH-LHD.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402842R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel role of the SOX4/CSNK2A1 axis in regulating TOP2A phosphorylation in breast cancer progression","authors":"Jiaqiong Zou,&nbsp;Ruiman Geng,&nbsp;Zhengkun Zhang,&nbsp;Xuxu Ji,&nbsp;Zhaoru Yin,&nbsp;Dingxue Wang,&nbsp;Rong Guo,&nbsp;Lihong Chen,&nbsp;Ji Liu","doi":"10.1096/fj.202401907RR","DOIUrl":"https://doi.org/10.1096/fj.202401907RR","url":null,"abstract":"<p>This study examines the critical role of DNA topoisomerase II alpha (TOP2A) phosphorylation in breast cancer progression, regulated by the SRY-box transcription factor 4 (SOX4)/Casein kinase II subunit alpha 1 (CSNK2A1) axis. Using integrated transcriptomic and proteomic analyses, data were sourced from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) databases. To explore the dataset, differential analysis, kinase-substrate enrichment analysis (KSEA), and weighted gene co-expression network analysis (WGCNA) were performed. Immune profiling, combined with survival analysis, revealed the prognosis linked to different immune profiles in breast cancer patients. In vitro experiments assessed the effect of SOX4 on CSNK2A1 promoter activity through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, dual-luciferase reporter assays, and chromatin immunoprecipitation (ChIP). The phosphorylation level of TOP2A was also measured. Cell proliferation, migration, and invasion were evaluated using cell counting kit-8 (CCK-8), colony formation, and Transwell assays. In vivo studies extended to mouse models, where the effect of SOX4 on CSNK2A1-TOP2A phosphorylation was analyzed about tumor growth and metastasis. The results showed that upregulation of SOX4 increases CSNK2A1 transcription, which in turn promotes TOP2A phosphorylation and accelerates breast cancer progression. The clinical analysis identified three immune profiles, with the intermediate profile associated with a poorer prognosis, possibly due to enhanced TOP2A phosphorylation mediated by SOX4/CSNK2A1. Silencing SOX4 significantly reduced cell proliferation, migration, invasion, and tumor growth in vivo by lowering CSNK2A1-TOP2A phosphorylation. These findings highlight the therapeutic potential of targeting the SOX4/CSNK2A1 axis in breast cancer and provide insight into its mechanism through TOP2A phosphorylation.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiles of gut microbiota and metabolites for high risk of transgenerational depression-like behavior by paternal methamphetamine exposure","authors":"Yuanyuan Zhang,&nbsp;Tao Hu,&nbsp;Xinyu Wang,&nbsp;Nongyuan Sun,&nbsp;Qinglong Cai,&nbsp;Hee Young Kim,&nbsp;Yu Fan,&nbsp;Dekang Liu,&nbsp;Xiaowei Guan","doi":"10.1096/fj.202402839R","DOIUrl":"https://doi.org/10.1096/fj.202402839R","url":null,"abstract":"<p>Parental substance abuse increases the risk of neurological and psychiatric disorders in offsprings. However, its underlying mechanism remains elusive. Our previous study demonstrated that long-term exposure to methamphetamine (Meth), a psychostimulant drug with high addiction potential, remarkably alters the gut microbiome and metabolites in male mice, which contribute to Meth-induced anxiety-like behaviors. The current study aimed to investigate whether gut microbiota and metabolism serve as potential peripheral targets for transgenerational mental problems by paternal Meth exposure. We found that paternal Meth exposure induced depression-like behaviors both in the first (F1) and the second (F2) generations of male mice. Further, the depletion of gut bacteria through antibiotic treatments normalized the depression-like behaviors to normal levels in both F1 and F2 male mice. Then, alterations in gut bacterial composition were observed in both F1 and F2 male mice. Specifically, <i>Eubacterium_ruminantium_group, Enterorhabdus, Alloprevotella</i>, and <i>Parabacteroides</i> were the commonly affected bacterial taxa in F1 and F2 male mice. In addition, the results of alterations in gut metabolism showed that LPC 14:1-SN1 emerged as the consistently altered metabolite in the colons of F1 and F2 male mice. Taken together, our findings provide the first evidence that paternal Meth exposure enhances depression-like behaviors in F1 and F2 male mice, potentially mediated by the gut microbiome and metabolism.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring a novel risk model based on core disulfidptosis-related genes in periodontitis: Bioinformatics analyses and experimental validation","authors":"Yiqiang Yang,&nbsp;Qi Liu,&nbsp;Xun Lu,&nbsp;Yuran Wang,&nbsp;Xue Tian,&nbsp;Jiahui Yang,&nbsp;Jia Chen","doi":"10.1096/fj.202401986R","DOIUrl":"https://doi.org/10.1096/fj.202401986R","url":null,"abstract":"<p>Bacteria in dental plaque invade periodontal tissues, causing chronic inflammation known as periodontitis. Despite advancements in understanding periodontitis, its molecular pathogenesis remains incompletely elucidated. In this study, a total of 247 samples were retrieved from the Gene Expression Omnibus (GEO) database, comprising 183 from individuals with periodontitis and 64 from healthy controls. Differentially expressed DRGs (DE-DRGs) were identified, and their expression correlations were analyzed. Immune cell infiltration and its association with DE-DRGs were assessed. Gene Set Variation Analysis (GSVA) was performed to determine key functions and pathways related to DE-DRGs. Characteristic DE-DRGs (CDE-DRGs) were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and a risk model and personalized nomogram were constructed. Model performance was validated through calibration and decision curve analysis (DCA). External experiments, including qRT-PCR and Western blot, confirmed the differential expression of DE-DRGs. Fourteen DE-DRGs were identified. Expression analysis revealed a strong synergistic correlation between MYH9 and ACTB (coefficient = 0.86) and an antagonistic correlation between NCKAP1 and FLNA (coefficient = −0.52). Immune profiling showed significant differences in the proportions of 22 immune cell types between groups, with 14 DE-DRGs correlated with immune infiltration levels. Cluster analysis of periodontitis samples revealed distinct patterns of DE-DRGs expression and immune cell infiltration across two clusters. A risk model incorporating four CDE-DRGs (DSTN, SLC7A11, SLC3A2, and RPN1) was developed, alongside a personalized nomogram for predicting periodontitis risk. qRT-PCR and Western blot analyses demonstrated downregulation of DSTN, SLC3A2, IQGAP1, CD2AP, and NCKAP1 and upregulation of SLC7A11, RPN1, FLNA, MYH9, TLN1, ACTB, MYH10, CAPZB, and PDLIM1 in periodontitis tissues. This study identified key DRGs in periodontitis, developed a predictive risk model and nomogram, and detailed the immune infiltration profile and its association with DRGs. These findings provide insights into the molecular pathogenesis of periodontitis and suggest potential strategies for personalized risk assessment, early diagnosis, and targeted therapy.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prussian blue nanoparticles prevent RANKL-induced osteoclastogenesis by scavenging ROS and inactivating NF-κB/MAPK signaling pathways","authors":"Jiancheng Yang,&nbsp;Qinghua Tang,&nbsp;Siyu Li,&nbsp;Lei Yang,&nbsp;Ming Yang,&nbsp;Qingmei Li,&nbsp;Yan Feng,&nbsp;Mingming Pan,&nbsp;Yuhong Zeng","doi":"10.1096/fj.202402646R","DOIUrl":"https://doi.org/10.1096/fj.202402646R","url":null,"abstract":"<p>The accumulation of intracellular reactive oxygen species (ROS) is widely recognized to stimulate the development of osteoclasts, a crucial factor in the onset of osteoporosis. The ROS scavenging capability of Prussian blue nanoparticles (PBNPs) is exceptional, and they possess excellent biocompatibility. However, the effects of PBNPs on osteoporosis remain unknown. Present study aimed to investigate whether PBNPs could inhibit osteoclast differentiation and prevent ovariectomy (OVX)-induced bone loss by suppressing ROS. In vitro experiments demonstrated that PBNPs attenuated osteoclastogenesis and downregulated the expression of osteoclast-related genes. Mechanistically, PBNPs reduce cellular ROS by blocking RANKL-induced ROS generation and increasing the expression of ROS scavenging enzymes, which in turn block the NF-κB, ERK, JNK, and p38 pathways, thereby reducing NFATc1 signaling. According to in vivo experimental results, OVX caused a significant rise in ROS in the bone marrow, an increase in osteoclastic number on the bone surface, and substantial bone loss; however, PBNPs significantly reduced ROS and successfully protected OVX-induced bone damages. In conclusion, this study showed for the first time that PBNPs prevented OVX-induced bone loss and attenuate osteoclastogenesis, indicating that PBNPs may be a viable alternative therapy for the management of osteoclast-associated bone disorders.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CETP expression in females increases body metabolism under both cold exposure and thermoneutrality contributing to a leaner phenotype","authors":"Júlia Z. Castelli,&nbsp;Helena F. Raposo,&nbsp;Claudia D. C. Navarro,&nbsp;Carolina M. Lazaro,&nbsp;Marina R. Sartori,&nbsp;Ana Paula Dalla Costa,&nbsp;Pedro A. S. Nogueira,&nbsp;Lício A. Velloso,&nbsp;Anibal E. Vercesi,&nbsp;Helena C. F. Oliveira","doi":"10.1096/fj.202402843RR","DOIUrl":"https://doi.org/10.1096/fj.202402843RR","url":null,"abstract":"<p>Susceptibility to obesity differs depending on the genetic background and housing temperatures. We have recently reported that CETP expressing female mice are leaner due to increased lipolysis, brown adipose tissue (BAT) activity, and body energy expenditure compared to nontransgenic (NTg) littermates under standard housing temperature (22°C). The aim of this study is to evaluate how CETP expression affects body temperature, composition, and metabolism during cold exposure (4°C) and thermoneutrality (30°C). When submitted to cold, CETP mice maintained rectal temperature, body weight, and food intake similarly to NTg mice along acute or chronic exposure to 4°C. The body oxygen consumption in response to an isoproterenol challenge was 21% higher at 22°C, and 41% higher after 7 days of cold exposure in CETP than in NTg mice. In addition, BAT biopsies from CETP mice showed reduced lipid content and increased basal oxygen consumption rates. Under thermoneutrality (30°C), when BAT activity is inhibited, CETP mice showed higher rectal and tail temperatures, increased food intake, and increased energy expenditure. Lean mass was elevated and fat mass reduced in CETP mice kept at 30°C. In this thermoneutral condition, soleus muscle, but not gastrocnemius or liver of CETP mice, showed increased mitochondrial respiration rates. These data indicate that CETP expression confers a greater capacity of elevating body metabolic rates at both cold exposure, through BAT activity, and at thermoneutrality, through increased muscle metabolism. Thus, the CETP expression levels in females should be considered as a new influence in the contexts of obesity and metabolic disorders propensity.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}