The FASEB Journal最新文献

{"title":"Retinoid X receptor agonist 9CDHRA mitigates retinal ganglion cell apoptosis and neuroinflammation in a mouse model of glaucoma","authors":"Devaraj Basavarajappa,&nbsp;Nitin Chitranshi,&nbsp;Seyed Shahab Oddin Mirshahvaladi,&nbsp;Veer B. Gupta,&nbsp;Viswanthram Palanivel,&nbsp;Gabriella E. Parrilla,&nbsp;Akanksha Salkar,&nbsp;Mehdi Mirzaei,&nbsp;András M. Komáromy,&nbsp;Wojciech Krezel,&nbsp;Stuart L. Graham,&nbsp;Vivek Gupta","doi":"10.1096/fj.202402642R","DOIUrl":"https://doi.org/10.1096/fj.202402642R","url":null,"abstract":"<p>Glaucoma, a leading cause of irreversible blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs) and optic nerve damage, often associated with elevated intraocular pressure (IOP). Retinoid X receptors (RXRs) are ligand-activated transcription factors crucial for neuroprotection, as they regulate gene expression to promote neuronal survival via several biochemical networks and reduce neuroinflammation. This study investigated the therapeutic potential of 9-cis-13,14-dihydroretinoic acid (9CDHRA), an endogenous retinoid RXR agonist, in mitigating RGC degeneration in a high-IOP-induced experimental model of glaucoma. We administered 9CDHRA to glaucomatous mice eyes via intravitreal injections and assessed its effects on endoplasmic reticulum (ER) stress markers, glial cell activation, and RGC survival. Our findings demonstrated that 9CDHRA treatment significantly protected inner retinal function and retinal laminar structure in high-IOP glaucoma. The treatment reduced ER stress markers, increased protein lysine acetylation, and diminished glial cell activation, leading to a significant decrease in apoptotic cells under glaucomatous conditions. These results suggest that 9CDHRA exerts neuroprotective effects by modulating key pathogenic pathways in glaucoma, highlighting its potential as a novel therapeutic strategy for preserving vision in glaucoma.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 6","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402642R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602741","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":"Nobiletin-mediated autophagy mitigates nanoplastic-induced toxicity in human intestinal Caco-2 cells","authors":"Junho Yu,&nbsp;Ji-Hwan Yoon,&nbsp;Miey Park,&nbsp;Hae-Jeung Lee","doi":"10.1096/fj.202402761R","DOIUrl":"https://doi.org/10.1096/fj.202402761R","url":null,"abstract":"<p>The presence of nanoplastics (NPs), which cause oxidative stress and damage to the cell structure due to the breakdown of microplastics (MPs), poses considerable ecological and health challenges. This study investigated the protective role of nobiletin (NOB), a flavonoid derived from citrus peel, in modulating autophagy and mitigating NP-induced toxicity in human intestinal Caco-2 cells. The Caco-2 cells were treated with NPs and varying concentrations of NOB to evaluate cell viability, apoptosis, and autophagic activity. We observed that exposure to NPs resulted in a concentration-dependent decrease in cell viability and an increase in the expression of apoptosis markers. Exposure to NPs reduced Caco-2 cell viability and disrupted autophagic processes by decreasing LC3B and increasing p62 levels, indicating impaired autophagy. NOB treatment reversed these effects by enhancing autophagic activity by upregulating LC3B and downregulating p62. Furthermore, NOB improved lysosomal integrity and decreased apoptotic markers such as Bax and cleaved caspase-3 while increasing Bcl-2 expression. NOB also facilitated the nuclear translocation of transcription factor EB through activating AMP-activated protein kinase (AMPK) and inhibiting mechanistic target of rapamycin (mTOR), promoting cellular detoxification and homeostasis. NOB has the potential as a therapeutic agent that leverages the autophagic pathway to mitigate the adverse effects of NPs, suggesting a novel approach for managing NPs toxicity in human intestinal Caco-2 cells.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 6","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402761R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595535","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":"Activation of SIK2 inhibits gluconeogenesis and alleviates lipogenesis-induced inflammatory response by SIK2-CRTC2-ACC1 in hepatocytes of large yellow croaker (Larimichthys crocea)","authors":"Shangzhe Han,&nbsp;Xiaojun Xiang,&nbsp;Xinwen Zhang,&nbsp;Lin Ou,&nbsp;Qiangde Liu,&nbsp;Xiang Xu,&nbsp;Jinze Zhang,&nbsp;Tingting Hao,&nbsp;Jianlong Du,&nbsp;Yueru Li,&nbsp;Kangsen Mai,&nbsp;Qinghui Ai","doi":"10.1096/fj.202402628R","DOIUrl":"https://doi.org/10.1096/fj.202402628R","url":null,"abstract":"<p>As an important kinase that maintains metabolic homeostasis, salt-induced kinase 2 (SIK2) inhibits adipogenesis in adipocytes and regulates mammalian glucose metabolism. Excessive lipid accumulation can lead to an inflammatory response, and SIK2 also controls the expression of inflammatory cytokines. However, the precise mechanisms and interconnections through which SIK2 modulates these processes remain incompletely understood. The present study explores the regulatory role of SIK2 in hepatic glucose and lipid metabolism and lipogenesis-induced inflammatory response of <i>Larimichthys crocea</i>. We found that palmitic acid or glucose reduces <i>sik2</i> mRNA expression, while its expression increases in response to insulin. Further, SIK2 reduces glucose content by inhibiting gluconeogenesis and activating insulin signaling pathways. Meanwhile, SIK2 overexpression decreases lipogenesis-related gene expression and increases lipolysis-related gene expression, alleviating hepatocyte lipid accumulation. Due to sequence conservation, SIK2 mutants are constructed. Only the T176A mutant weakens the inhibition of wt-SIK2 on the acetyl-CoA carboxylase 1 (ACC1) promoter through cyclic AMP-responsive element-binding protein (CREB). It increases the expression of CREB-regulated transcription coactivator 2 (CRTC2) in the nucleus. Then, ACC1 inhibition attenuates the inflammatory response. SIK2 alleviates the inflammatory response by reducing pro-inflammatory cytokines expression and inactivating the mitogen-activated protein kinase (MAPK) pathway. Furthermore, similar results were obtained by inhibiting SIK2 in vivo. Overall, this study explores the role of SIK2 in hepatic glucose and lipid metabolism and lipogenesis-induced inflammatory response in fish for the first time, which provides insights into the functional protection of SIK2 in vertebrate evolution and may serve as a target for the treatment of nutritional and immune disorders.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 6","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595534","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":"Intensive stress impedes hair follicle growth through triggering cell cycle arrest of hair follicle stem cells","authors":"Xinhui Wang,&nbsp;Yumiao Lin,&nbsp;Lingchen Yan,&nbsp;Binqi Wu,&nbsp;Kechen Zhu,&nbsp;Xusheng Wang,&nbsp;Zhongjie Liu","doi":"10.1096/fj.202403343R","DOIUrl":"https://doi.org/10.1096/fj.202403343R","url":null,"abstract":"<p>The detrimental effects of stress on hair growth are supported by empirical and experimental evidence, but the specific impact and mechanisms remain poorly understood. Here we utilized two intensive stress paradigms, repeated resiniferatoxin (RTX) injections and physical restraint in mice, to assess the effects of intensive stress on hair follicle growth after depilation. Initially, macroscopic pictures of the mice dorsal skin and HE staining showed a substantial inhibition of depilation-induced hair growth in both telogen and anagen hair follicle growth under intensive stress induced by RTX and restraint. Mechanistically, single-cell RNA sequencing analysis of mice skin under intensive stress highlighted a significant downregulation of cell-cycle genes and upregulation of the cAMP signaling pathway in <i>Lgr5</i>^<i>+</i> hair follicle stem cells (HFSCs). Notably, the sympathetic nervous system was activated under intensive stress. Then, the neurotransmitter noradrenaline (NA), a secretion of the sympathetic nervous system, and 8-bromo-cAMP, a cAMP analog, were used to manifest the inhibitory effect of the sympathetic nervous system on HaCaT cell proliferation, as evidenced by the results of decreased cell activity and colony formation, downregulated expression of cyclin D1/2 and CDK4, the increased percentage of G0/G1, and decreased percentage of the S phase. Importantly, hair follicle regeneration was significantly inhibited by NA and 8-bromo-cAMP in mice. Collectively, our study suggests that intensive stress inhibits the cell cycle of hair follicle growth through the sympathetic nervous system/NA/cAMP pathway, thus providing a mechanistic insight into intensive stress-induced inhibition in hair follicle growth.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581807","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":"Loss of the vitamin A receptor RBPR2 in mice disrupts whole-body retinoid homeostasis and the quantitative balance regulating retinylidene protein synthesis","authors":"Rakesh Radhakrishnan,&nbsp;Matthias Leung,&nbsp;Anjelynt Lor,&nbsp;Swati More,&nbsp;Glenn P. Lobo","doi":"10.1096/fj.202403090R","DOIUrl":"https://doi.org/10.1096/fj.202403090R","url":null,"abstract":"<p>The distribution of stored dietary vitamin A/all-<i>trans</i>-retinol (ROL) from the liver throughout the body is critical for maintaining retinoid function in peripheral tissues and for generating visual pigments for photoreceptor cell function. ROL circulates in the blood bound to the retinol binding protein 4 (RBP4) as RBP4-ROL. Two membrane receptors, RBPR2 in the liver and other non-ocular tissues, and STRA6 in the eye are proposed to bind circulatory RBP4 and this mechanism facilitates the internalization of ROL. Herein, we conducted a longitudinal study to investigate the importance of RBPR2 and influence of vitamin A content in the diet on whole-body retinoid homeostasis and its effects on chromophore production in the support of visual function. <i>Rbpr2</i>-knockout (<i>Rbpr2</i>^{<i>−/−</i>}) and wild-type mice were fed a vitamin A sufficient (VAS) or a vitamin A deficient (VAD) diet. After 3-months of dietary intervention and compared with WT mice, <i>Rbpr2</i>^{<i>−/−</i>} mice showed significantly lower hepatic ROL and retinyl ester content, and decreased chromophore concentrations, manifesting in dysfunctional scotopic and photopic electroretinogram (ERG) responses. These phenotypes were more severe in VAD <i>Rbpr2</i>^{<i>−/−</i>} mice, when compared with VAS <i>Rbpr2</i>^{<i>−/−</i>} mice. After 6 months of dietary intervention, while WT mice were able to maintain retinoid homeostasis in peripheral tissues, <i>Rbpr2</i>^{<i>−/−</i>} mice showed elevated serum apo-RBP4 protein, decreased retinoid content in peripheral tissues including the liver and the eye causing an accumulation of apoprotein opsin in photoreceptors, which resulted in delayed rod and cone opsin regeneration. Together, our analyses characterize the molecular events underlying nutritional blindness in a novel mouse model and indicate that the vitamin A receptor, RBPR2, is required for whole-body retinoid homeostasis, which supports chromophore production and visual function under variable conditions of dietary vitamin A intake throughout the lifespan of the animal.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403090R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581806","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":"Toxoplasma survives the loss of key enzymes of peroxide and glutathione metabolism","authors":"Qinghong Guo,&nbsp;Jiajia Pan,&nbsp;Xuefang Guo,&nbsp;Meng Zhao,&nbsp;Huiyu Du,&nbsp;Mengting Wang,&nbsp;Marcel Deponte,&nbsp;Xinhua Zhong,&nbsp;Lihua Xiao,&nbsp;Yaoyu Feng,&nbsp;Ningbo Xia","doi":"10.1096/fj.202402341R","DOIUrl":"https://doi.org/10.1096/fj.202402341R","url":null,"abstract":"<p><i>Toxoplasma gondii</i> is an obligate intracellular protozoan parasite that replicates rapidly in a variety of host cells. The parasite encodes diverse enzymes of glutathione and peroxide metabolism, but their physiological roles remain poorly understood. Herein, we shed a new perspective on the functions and relevance of the peroxiredoxin and glutathione metabolism in the zoonotic pathogen <i>T. gondii</i>. We show that two cytosolic peroxidases (<i>Tg</i>PRX1, <i>Tg</i>PRX2), a mitochondrial peroxiredoxin (<i>Tg</i>PRX3), and the cytosolic glutathione reductase (<i>Tg</i>GR2), glutamate-cysteine ligase (<i>Tg</i>GCL), and glutathione synthetase (<i>Tg</i>GS) are not required for the lytic cycle of <i>T. gondii</i> under standard growth conditions. However, mutants lacking the gene for either <i>Tg</i>PRX1 or <i>Tg</i>GR2 exhibited increased susceptibility to exogenous hydrogen peroxide compared to wild-type parasites. Furthermore, we found that the combined deletion of <i>Tg</i>PRX1 and <i>Tg</i>PRX2 led to a notable impairment of parasite growth, suggesting a functional redundancy between the two peroxidases. Finally, our results show that the apicoplast glutathione reductase (<i>Tg</i>GR1) is required for normal parasite growth in vitro and in vivo but is not essential for parasite survival. Our findings highlight that the redox metabolism of <i>Toxoplasma</i> is surprisingly robust and flexible, allowing the parasite to survive under the loss of several key enzymes of peroxide and glutathione metabolism.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581772","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":"SNAI2, a potential crossing point between cancer and cardiovascular disease","authors":"Zihao Liu,&nbsp;Yingzi Wang,&nbsp;Lei Li,&nbsp;Linlu Liu,&nbsp;Yuhao Li,&nbsp;Zhixin Li,&nbsp;Yucheng Xie,&nbsp;Fengxu Yu","doi":"10.1096/fj.202500198R","DOIUrl":"https://doi.org/10.1096/fj.202500198R","url":null,"abstract":"<p>Cancer and cardiovascular disease remain the leading causes of morbidity and mortality worldwide, and the two separate disease entities share several similarities and possible interactions. Patients with cancer may have underlying cardiovascular disease, which is often exacerbated by the stress of tumor growth or treatment. At the same time, cardiotoxicity induced by anti-cancer therapies or the malignant process itself can lead to new cardiovascular diseases. Efforts have been made to find a rational explanation for this phenomenon. As a classical tumor-promoting factor, we notice that SNAI2 simultaneously plays an important pathogenic role in cardiovascular diseases. Moreover, there are several striking parallels in the mechanisms of cancer and CVD, such as shared risk factors (e.g., smoking and diabetes), cellular phenotypic switching, and metabolic remodeling, all of which are mediated by SNAI2. This review aims to summarize SNAI2's role in the core mechanisms linking cancer and CVD, as well as explore therapeutic approaches targeting SNAI2 and also seeks to provide insights into the common mechanisms underlying both cancer and CVD.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500198R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581773","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":"Di-(2-ethylhexyl)-phthalate disrupts mouse placental growth by regulating the cell cycle of mouse placental trophoblasts through the Trim38-p53 signaling axis","authors":"Yafei Guo,&nbsp;Bowen Li,&nbsp;Nanjun Zhang,&nbsp;Yu Yan,&nbsp;Shuran Shao,&nbsp;Lixia Yang,&nbsp;Ping Wu,&nbsp;Hongyu Duan,&nbsp;Kaiyu Zhou,&nbsp;Yimin Hua,&nbsp;Chuan Wang","doi":"10.1096/fj.202402049RR","DOIUrl":"https://doi.org/10.1096/fj.202402049RR","url":null,"abstract":"<p>Di-(2-ethylhexyl)-phthalate (DEHP) is a common endocrine disruptor that causes very serious environmental pollution. Recent studies have described that DEHP exerts detrimental effects on key processes of placental development, including implantation, differentiation, invasion, and angiogenesis. However, its effects on the proliferation of placental trophoblasts and related regulatory mechanisms remain elusive. This study demonstrated that maternal DEHP exposure significantly disrupted placental growth. Similarly, transcriptomic and proteomic analyses of DEHP-treated placental tissues revealed that DEHP may disrupt placental growth by affecting the cell cycle of placental trophoblasts. Further analyses validated that DEHP inhibited the growth of mouse placental trophoblasts by significantly upregulating the expression of the p53 protein, which arrests the cell cycle. Mechanistically, Tripartite motif protein 38 (Trim38) was identified as a target protein of MEHP, with Trim38 binding to p53 and downregulating p53 expression by promoting its ubiquitination-proteasomal degradation. Interestingly, MEHP could inhibit the Trim38-regulated ubiquitination degradation of p53 and up-regulate p53 protein expression, which in turn inhibited the cell cycle and, ultimately, mouse placental trophoblast growth. In conclusion, DEHP disrupted mouse placental growth by inhibiting the cell cycle of mouse placental trophoblasts via the Trim38-p53 signaling axis. Overall, this study provides a theoretical reference for elucidating the mechanism underlying DEHP-induced placental toxicity.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402049RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581775","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":"Polo-like kinase2 regulates renal tubulointerstitial fibrosis via notch signaling pathway in diabetic kidney disease","authors":"Jiayi Luo,&nbsp;Haibin Xu,&nbsp;Cailin Su,&nbsp;Wenhui Dong,&nbsp;Manlu Xiao,&nbsp;Nan Xiao,&nbsp;Yijie Jia,&nbsp;Yaoming Xue","doi":"10.1096/fj.202402793R","DOIUrl":"https://doi.org/10.1096/fj.202402793R","url":null,"abstract":"<p>Renal tubulointerstitial fibrosis is considered as an important pathological feature of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. Polo-like kinase2 (PLK2) is a known player in the regulation of organ fibrosis. Herein, we investigated the expression and function of PLK2 in renal tubular epithelial cells in DKD. Data from the GSE30529 datasets were subjected to analyze the differentially expressed genes (DEGs) in non-diabetic and diabetic renal tubule samples. Molecular docking analysis and Co-IP assay were performed to investigate the interaction between PLK2 and NOTCH1. Immunohistochemistry, immunofluorescent staining, qRT-PCR, and western blot were performed. Our research revealed an increased expression of PLK2 in both DKD mouse kidney tissues and HK-2 cells stimulated by high glucose (HG). Silencing PLK2 remarkably reduced the expression of the renal fibrosis-related markers fibronectin (FN), connective tissue growth factor (CTGF) and alpha smooth muscle actin(αSMA). Furthermore, we verified the interaction between PLK2 and NOTCH1. Silencing PLK2 significantly inhibited the activation of the Notch signaling pathway, and concurrently overexpressing HES1 rescued the downregulation of FN, CTGF, and αSMA induced by transfecting si-PLK2. Finally, we found that treatment with DAPT suppressed the activation of the Notch signaling pathway and reversed the progression of renal fibrosis caused by HG. This study demonstrates that PLK2 mediates renal tubulointerstitial fibrosis in DKD by activating the Notch signaling pathway, suggesting that PLK2 may be a potential therapeutic target for DKD.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402793R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581774","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":"Gut microbiota alteration was related to subclinical hypothyroidism and dyslipidemia in mice","authors":"Ru Wang,&nbsp;Xiaqing Yu,&nbsp;Haidong Cai,&nbsp;Ganghua Lu,&nbsp;Dingwei Gao,&nbsp;Mengyu Zhang,&nbsp;Li Chai,&nbsp;Wanwan Yi,&nbsp;Zhongwei Lv","doi":"10.1096/fj.202402289RR","DOIUrl":"https://doi.org/10.1096/fj.202402289RR","url":null,"abstract":"<p>Gut microbiota has a close connection to different thyroid disorders, yet research on its links to subclinical hypothyroidism (SCH) remains limited and insufficient. In this study, we explored the potential relationship between the gut microbiota and SCH, as well as dyslipidemia in SCH mice. The SCH mouse model was induced using methimazole. The composition of the gut microbiota from mice was then analyzed through 16S rRNA gene sequencing technology. An antibiotic disruption experiment was used to assess how gut microbiota imbalance impacts thyroid function. The SCH mouse models were constructed and accompanied by significant dyslipidemia. The results revealed no significant differences in the <i>Firmicutes</i> to <i>Bacteroidota</i> ratio or α-diversity in gut microbiota from SCH and control mice, and in β-diversity, there was a noticeable but small difference between the groups. 14 differential genera between the two groups identified through LEfSe analysis were significantly correlated with serum lipid levels. Furthermore, the results of the antibiotic disruption experiment demonstrated that gut microbiota imbalance exacerbated the hypothyroidism in mice. The present results suggest that subclinical hypothyroidism has not yet caused significant changes in gut microbiota homeostasis, but gut microbiota plays an important role in regulating thyroid function and is closely associated with dyslipidemia in SCH. This study could help understand the relationship between gut microbiota and SCH, and offer new perspectives on dyslipidemia management in SCH.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402289RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564649","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}