Robin van Eenige, Carlijn A Hoekx, Aashley S D Sardjoe Mishre, Maaike E Straat, Mariëtte R Boon, Borja Martinez-Tellez, Patrick C N Rensen, Hermien E Kan
{"title":"Cold exposure and thermoneutrality similarly reduce supraclavicular brown adipose tissue fat fraction in fasted young lean adults.","authors":"Robin van Eenige, Carlijn A Hoekx, Aashley S D Sardjoe Mishre, Maaike E Straat, Mariëtte R Boon, Borja Martinez-Tellez, Patrick C N Rensen, Hermien E Kan","doi":"10.1096/fj.202402415R","DOIUrl":"10.1096/fj.202402415R","url":null,"abstract":"<p><p>Brown adipose tissue (BAT) is a metabolically highly active tissue that dissipates energy stored within its intracellular triglyceride droplets as heat. Others have previously utilized MRI to show that the fat fraction of human supraclavicular BAT (scBAT) decreases upon cold exposure, compared with baseline (i.e., pre-cooling). However, comparisons to a control group that was not exposed to cold are largely lacking. We recently developed a non-invasive dynamic MRI protocol that allows for quantifying scBAT fat fraction changes over time. Here, we aimed to study the effect of cold exposure versus thermoneutrality on fat fraction changes in human scBAT. Ten young (mean age: 21.5 ± 0.7 years), lean (mean BMI: 21.7 ± 0.5 kg/m<sup>2</sup>), 12 h-fasted volunteers (9 females; 1 male) underwent up to 70 consecutive MRI scans each on two separate study visits in a cross-over design. Participants were exposed to a temperature of 32°C for 10 scans (i.e., ±16 min), which was then either lowered to 18°C (i.e., cold exposure) or was maintained at 32°C (i.e., thermoneutrality). Dynamic fat fraction changes were quantified, and self-reported thermal perception scores were monitored. The fat fraction in scBAT decreased over time upon cold exposure (r = -.222, p < .001). Interestingly however, we also observed a decrease in scBAT fat fraction over time upon thermoneutrality (r = -.212, p < .001). No difference was observed between the two temperature conditions (p = .55), while self-reported thermal perception scores were consistently higher (i.e., colder) upon cold exposure. In the trapezius muscle and the humerus bone as control tissues, the fat fraction was unaffected in both temperature conditions. The fat fraction in subcutaneous white adipose tissue (sWAT) however, also decreased over time upon cold exposure (r = -.270, p < .001) and during thermoneutrality (r = -.190, p < .001), again with no difference (p = .92) between the two temperature conditions. In conclusion, our results show that in 12 h-fasted, healthy individuals cold exposure and thermoneutrality similarly reduce the fat fraction within scBAT and sWAT. While we interpret that the cold exposure was sufficient to induce thermogenesis, we suggest that an increased lipolytic activity within adipocytes, as a consequence of fasting, may be the primary cause of the decreased fat fraction in both sWAT and scBAT in our study. The current study highlights the potential influence of fasting on the fat fraction in scBAT and stresses the importance of inclusion of a thermoneutral control group in studies investigating the BAT-modulating effect of cold exposure.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 1","pages":"e70307"},"PeriodicalIF":4.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967158","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}
Kangcheng Zhao, Yukun Zhang, Zhiwei Liao, Weifeng Zhang, Gaocai Li, Pengzhi Shi, Zhangrong Cheng, Yuhang Chen, Shuai Li, Kun Wang, Yu Song, Xiaobo Feng, Ran An, Cao Yang
{"title":"Melatonin mitigates intervertebral disc degeneration by suppressing NLRP3 inflammasome activation via the EGR1/DDX3X pathway","authors":"Kangcheng Zhao, Yukun Zhang, Zhiwei Liao, Weifeng Zhang, Gaocai Li, Pengzhi Shi, Zhangrong Cheng, Yuhang Chen, Shuai Li, Kun Wang, Yu Song, Xiaobo Feng, Ran An, Cao Yang","doi":"10.1096/fj.202302453RRR","DOIUrl":"https://doi.org/10.1096/fj.202302453RRR","url":null,"abstract":"<p>Intervertebral disc degeneration (IVDD), is one of the leading causes of low back pain. Inflammation is considered to be the main pathophysiological process of IVDD. The nucleotide-binding domain and leucine-rich pyrin domain containing 3 (NLRP3) inflammasome-mediated inflammatory responses are critically involved in the progression of IVDD. Melatonin is known for its anti-inflammatory and antioxidant effects. However, little is known about the potential effects of melatonin in the pathological process of IVDD. We found that the expression of EGR1, DDX3X, and NLRP3 inflammasome increased and extracellular matrix (ECM) degraded in IVDD. With the application of EGR1 siRNA, the expression of DDX3X and the activation of NLRP3 inflammasome were inhibited in stress-induced NP cells. DDX3X/NLRP3 was regulated on dependence of EGR1. Besides, the utility of melatonin mitigated the EGR1-induced overproduction of DDX3X and activation of NLRP3 inflammasome, thus protecting cells from pyroptosis and ECM degradation. In vivo, in a rat IVDD model, melatonin was found to be able to delay the development of IVDD by imageological and histological evaluation. In conclusion, our study demonstrated that melatonin prevented IVDD progression by regulating EGR1/DDX3X/NLRP3 axis. Our study provides insight into melatonin as a new target for therapeutic approaches for IVDD.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868797","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":"Correction to “PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis”","authors":"","doi":"10.1096/fj.202403179","DOIUrl":"10.1096/fj.202403179","url":null,"abstract":"<p>Zhou G, Zhu F, Zhang H, et al. PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis. <i>The FASEB Journal</i>. 2023; 37:e22967. doi:10.1096/fj.202201995RR</p><p>The authors report a mistake in Figure 9E that occurred during image naming and selection. The images in panels Ctrl TAE and DSS PBS are similar to the images in Figure 6 representing PTK2B KO Ctrl and DSS, respectively. This error does not change the results or conclusions of the study. The authors apologize for the error.</p><p>The corrected Figure 9 is as follows:</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866093","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":"SMG5, a component of nonsense-mediated mRNA decay, is essential for the mouse spermatogonial differentiation and maintenance","authors":"Xiao Tan, Chengyan Chen, Xiyao Gao, Hua Wang, Youming Zhang, Tangliang Li","doi":"10.1096/fj.202402422R","DOIUrl":"10.1096/fj.202402422R","url":null,"abstract":"<p>Mammalian spermatogenesis is a tightly controlled cellular process including spermatogonial development and differentiation, meiosis of spermatocyte, and the morphological specification of haploid spermatozoa, during which the post-transcriptional gene regulations are vital but poorly understood. Nonsense-mediated mRNA decay (NMD), a highly conserved post-transcriptional regulatory mechanism of gene expression in eukaryotes, recently emerges as a licensing mechanism in cell fate transition, including stem cell differentiation and organogenesis. The function of NMD in spermatogonial development remains elusive. Here we found knockout of SMG5, an important component of the NMD machinery, in embryonic germ cells led to the failure of spermatogenesis and male infertility. SMG5 null resulted in defective differentiation and maintenance of spermatogonia, which affected initiation of meiosis, ultimately caused a “Sertoli cell-only” phenotype. Transcriptome analysis revealed that SMG5 loss led to serious defects in NMD with targets features including PTC, long 3′ UTR, and 5′ uORFs. Furthermore, SMG5 loss downregulates gene transcripts involved in spermatogonia expansion and differentiation. During the spermatogonial differentiation, the deletion of SMG5 led to hyperactivation of the p38 MAPK signaling pathway, which triggered widespread cell death. These results suggest that SMG5 mediated NMD plays an important role in spermatogenesis by regulating the p38 MAPK signaling pathway.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866102","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}
Khyati Girdhar, Keiichiro Mine, Jeffrey M. DaCosta, Mark A. Atkinson, Johnny Ludvigsson, Emrah Altindis
{"title":"Sex-specific cytokine, chemokine, and growth factor signatures in T1D patients and progressors","authors":"Khyati Girdhar, Keiichiro Mine, Jeffrey M. DaCosta, Mark A. Atkinson, Johnny Ludvigsson, Emrah Altindis","doi":"10.1096/fj.202402354R","DOIUrl":"10.1096/fj.202402354R","url":null,"abstract":"<p>Numerous studies have reported altered cytokine levels in type 1 diabetes (T1D) patients, yet findings remain inconsistent. In this pilot study, we tested the hypothesis that circulating immune markers exhibit sex-based differences in T1D, both prior to and after disease onset. We analyzed 47–48 cytokine, chemokine, and growth factor levels in two cohorts. To assess post-disease differences, we analyzed serum samples from 25 controls and 25 T1D patients. To examine pre-disease progression, we utilized samples from 21 control children and 16 T1D progressors, collected at age 5 years before disease onset. Across all T1D patients and controls, only macrophage colony-stimulating factor and interleukin (IL)-6 showed significant differences. However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Female T1D patients exhibited lower levels of inflammatory cytokines (tumor necrosis factor-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (macrophage inflammatory protein (MIP)-1α, regulated upon activation, normal T cell expressed and secreted, MIP-3) compared to female controls, differences that were not observed in males. Notably, IL-22 was lower in female T1D patients compared to female controls, whereas it was higher in male T1D patients compared to male controls. Male T1D patients showed elevated levels of growth factors (epidermal growth factor, platelet-derived growth factor-AB/BB) compared to male controls. In T1D progressors, growth-regulated alpha was lower compared to controls in both sexes. Multiple regression analysis further revealed associations between cytokine levels and factors such as age, BMI, and breastfeeding duration. Overall, our findings serve as a proof of concept, highlighting the importance of sex-specific differences in T1D pathogenesis. However, follow-up studies with larger sample sizes are needed to validate and generalize these results.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402354R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866098","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}
Lin Xu, Boao Liu, Honghui Ma, Enbo Qi, Jie Ma, Tingmin Chang, Jinghong Zhang, Wencheng Zhang, Weiqian Chen, Xuan Cao, Xiwen Xiong
{"title":"O-GlcNAc transferase promotes vascular smooth muscle calcification through modulating Wnt/β-catenin signaling","authors":"Lin Xu, Boao Liu, Honghui Ma, Enbo Qi, Jie Ma, Tingmin Chang, Jinghong Zhang, Wencheng Zhang, Weiqian Chen, Xuan Cao, Xiwen Xiong","doi":"10.1096/fj.202401649RR","DOIUrl":"10.1096/fj.202401649RR","url":null,"abstract":"<p>Vascular calcification (VC), associated with high cardiovascular mortality in patients with chronic kidney disease (CKD), involves osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). O-GlcNAcylation, a dynamic post-translational modification, is closely linked to cardiovascular diseases, including VC. However, the exact role and molecular mechanism of O-GlcNAc signaling in abnormal mineral metabolism-induced VC remain unclear. In the current study, we found that the levels of O-GlcNAc transferase (OGT) and global protein O-GlcNAcylation were significantly upregulated in the artery tissues of mouse calcification models and CKD patients with VC. To further delineate the in vivo role of OGT in VC, we generated <i>Ogt</i> smooth muscle cell-specific knockout mice and challenged them with 5/6 nephrectomy (5/6 Nx) or high-dose vitamin D3 to induce VC. Deletion of <i>Ogt</i> in VSMCs led to alleviated VC in response to 5/6 Nx or VD3. Moreover, elevated O-GlcNAcylation, induced by Thiamet-G, facilitated osteogenic transdifferentiation in VSMCs in response to phosphate, whereas OSMI-1, which reduces O-GlcNAcylation, exhibited an opposite phenotypic effect. Mechanistically, O-GlcNAc signaling enhanced the osteogenic conversion of VSMCs through regulation of canonical Wnt/β-catenin pathway. Indeed, β-catenin was O-GlcNAcylated by OGT and further increased its transcriptional activity in VSMCs. Furthermore, pharmacological activation of Wnt/β-catenin signaling largely reversed the diminished aortic calcification caused by <i>Ogt</i> ablation. Our findings demonstrate that smooth muscle O-GlcNAc signaling plays an important role in regulating hyperphosphatemia-induced VC and reveal that O-GlcNAcylation of β-catenin protein modulates its content and activity in VSMCs.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866096","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}
Andrew C. Hostler, William W. Hahn, Michael S. Hu, Robert Rennert, Katharina S. Fischer, Janos A. Barrera, Dominik Duscher, Michael Januszyk, Dominic Henn, Dharshan Sivaraj, Jonathan P. Yasmeh, Hudson C. Kussie, Maia B. Granoski, Jagannath Padmanabhan, Ivan N. Vial, Johannes Riegler, Joseph C. Wu, Michael T. Longaker, Kellen Chen, Zeshaan N. Maan, Geoffrey C. Gurtner
{"title":"Endothelial-specific CXCL12 regulates neovascularization during tissue repair and tumor progression","authors":"Andrew C. Hostler, William W. Hahn, Michael S. Hu, Robert Rennert, Katharina S. Fischer, Janos A. Barrera, Dominik Duscher, Michael Januszyk, Dominic Henn, Dharshan Sivaraj, Jonathan P. Yasmeh, Hudson C. Kussie, Maia B. Granoski, Jagannath Padmanabhan, Ivan N. Vial, Johannes Riegler, Joseph C. Wu, Michael T. Longaker, Kellen Chen, Zeshaan N. Maan, Geoffrey C. Gurtner","doi":"10.1096/fj.202401307R","DOIUrl":"10.1096/fj.202401307R","url":null,"abstract":"<p>C-X-C motif chemokine ligand 12 (CXCL12; Stromal Cell-Derived Factor 1 [SDF-1]), most notably known for its role in embryogenesis and hematopoiesis, has been implicated in tumor pathophysiology and neovascularization. However, its cell-specific role and mechanism of action have not been well characterized. Previous work by our group has demonstrated that hypoxia-inducible factor (HIF)-1 modulates downstream CXCL12 expression following ischemic tissue injury. By utilizing a conditional CXCL12 knockout murine model, we demonstrate that endothelial-specific deletion of CXCL12 (eKO) modulates ischemic tissue survival, altering tissue repair and tumor progression without affecting embryogenesis and morphogenesis. Loss of endothelial-specific CXCL12 disrupts critical endothelial–fibroblast crosstalk necessary for stromal growth and vascularization. Using murine parabiosis with novel transcriptomic technologies, we demonstrate that endothelial-specific CXCL12 signaling results in downstream recruitment of non-inflammatory circulating cells, defined by neovascularization modulating genes. These findings indicate an essential role for endothelial-specific CXCL12 expression during the neovascular response in tissue injury and tumor progression.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856145","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":"DeSUMOylating isopeptidase 1 participates in the faithful chromosome segregation and vincristine sensitivity","authors":"Yuki Ikeda, Ryuzaburo Yuki, Youhei Saito, Yuji Nakayama","doi":"10.1096/fj.202401560RR","DOIUrl":"10.1096/fj.202401560RR","url":null,"abstract":"<p>SUMOylation, the modification of proteins with a small ubiquitin-like modifier (SUMO), is known to regulate various cellular events, including cell division. This process is dynamic, with its status depending on the balance between SUMOylation and deSUMOylation. While the regulation of cell division by sentrin-specific protease (SENP) family proteins through deSUMOylation has been investigated, the role of another deSUMOylase, deSUMOylating isopeptidase 1 (DESI1), remains unknown. In this study, we explored DESI1's role in cell division. Knockdown of DESI1 accelerated cell division progression, leading to a significant increase in abnormal chromosome segregation. These phenotypes were rescued by re-expression of wild-type DESI1, but not catalytically inactive DESI1. DESI1 knockdown reduced the mitotic arrest caused by nocodazole, suggesting DESI1's involvement in the spindle assembly checkpoint (SAC). Localization of Aurora B, a key SAC regulator, at the metaphase chromosomes was reduced due to decreased Aurora B expression upon DESI1 knockdown. Consistently, DESI1 knockdown reduced transcription of FoxM1 target genes, such as Aurora B, cyclin B1, and CENP-F. The TCGA database showed that both decreased and increased DESI1 expression levels are associated with poor prognosis in patients with certain cancer types. Importantly, we found that DESI1 knockdown reduced sensitivity to vincristine by inducing mitotic slippage. These results suggest that DESI1 is required for faithful chromosome segregation via regulating FoxM1 transcriptional activity and thereby SAC activity in an isopeptidase activity-dependent manner. Our findings identified DESI1 as a novel regulator of cell division and a factor affecting cancer chemotherapy.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202401560RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856061","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}
Rodney Littlejohn, Josue Zambrano-Carrasco, Jianqiu Zou, Yi Lu, Elise Liu, Il-man Kim, Kai Jiao, Neal L. Weintraub, Jiliang Zhou, Jie Li, Huabo Su
{"title":"Neddylation drives myofibrillogenesis in the developing heart","authors":"Rodney Littlejohn, Josue Zambrano-Carrasco, Jianqiu Zou, Yi Lu, Elise Liu, Il-man Kim, Kai Jiao, Neal L. Weintraub, Jiliang Zhou, Jie Li, Huabo Su","doi":"10.1096/fj.202401380R","DOIUrl":"10.1096/fj.202401380R","url":null,"abstract":"<p>Neddylation is a highly conserved post-translational modification that plays critical roles in various cellular processes through the modulation of cullins and non-cullin substrates. While neddylation is known to be essential for embryonic development, tumor growth, and organogenesis of different tissues, its role in cardiogenesis remains unexplored. Here, we investigated the role of neddylation in early cardiac development by deleting the gene encoding a regulatory subunit of the NEDD8-specific E1 activating enzyme, <i>Nae1</i>, globally and in a heart-specific fashion via <i>Nkx2-5</i><sup>Cre</sup>. Global deletion of <i>Nae1</i> in mice led to embryonic lethality before embryonic day (E) 8.5, whereas cardiac-specific NAE1 knockout mice died at around E12.5 with pronounced cardiac effusion and peripheral hemorrhage, characteristic of cardiac failure. Histological analysis revealed significant thinning of the compact myocardium and reduced trabeculae in mutant hearts, which were accompanied by reduced cardiomyocyte proliferation. Unbiased transcriptomic analysis identified perturbations in cardiomyocyte proliferation and myofibril architecture in mutant hearts. Subsequent analysis showed that loss of NAE1 disrupted sarcomere assembly dysregulated the expression of several important contractile proteins, and impaired mitochondrial function in the developing heart, which was accompanied by downregulation of key cardiac transcription factors including NKX2-5 and SRF. Collectively, our findings demonstrate the essential role of neddylation in cardiogenesis at least in part by driving cardiomyocyte proliferation and myofibrillogenesis.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856200","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}
Lupann Rieger, Thomas Molina, Paul Fabre, Karine Greffard, Ornella Pellerito, Junio Dort, Jean-François Bilodeau, Nicolas A. Dumont
{"title":"Transcriptomic and lipidomic profiling reveals distinct bioactive lipid signatures in slow and fast muscles and highlights the role of resolvin-D2 in fiber type determination during myogenesis","authors":"Lupann Rieger, Thomas Molina, Paul Fabre, Karine Greffard, Ornella Pellerito, Junio Dort, Jean-François Bilodeau, Nicolas A. Dumont","doi":"10.1096/fj.202401747R","DOIUrl":"10.1096/fj.202401747R","url":null,"abstract":"<p>Skeletal muscles are predominantly composed of long, multinucleated muscle fibers, classified according to their metabolic and contractile phenotype. The determination of fiber types is influenced by various factors (e.g., innervation, hormones, physical demand). Our laboratory and others showed that resolvins, lipid mediators derived from omega-3 fatty acids, promote muscle regeneration and function after an injury or in models of muscular dystrophies; however, the effect of resolvins on the determination of muscle phenotype remains unknown. Here, we investigated the impact of lipid mediators on muscle phenotype during myogenesis. Transcriptomics analysis of single-nuclei RNAseq data sets revealed that the enzymes responsible for bioactive lipids biosynthesis are differentially expressed in slow fibers versus fast fibers. Lipidomics analysis of slow-twitch muscle (soleus) versus fast-twitch muscle (tibialis anterior) showed that the levels of lipids derived from arachidonic acid are similar between muscle groups, but lipids derived from alpha-linolenic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid are enriched in slow-twitch muscle. Screening for different lipids in vitro showed that resolvin-D2 enhances the formation of myotubes expressing the slow myosin heavy chain isoform. In vivo, the administration of resolvin-D2 enhances muscle strength, increases myofiber size, and affects fiber typing in injured muscles but not in uninjured muscles. Resolvin-D2 promoted the transition toward the dominant fiber types in regenerating muscle (i.e., type I in the slow-twitch soleus and type IIB in the fast-twitch tibialis anterior muscle), suggesting its participation in fiber typing in conjunction with other factors. Overall, these findings identified new roles of bioactive lipids in the regulation of fiber typing, which could have therapeutic applicability in muscle injuries or dystrophies.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"38 24","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202401747R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856422","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}