Molecular Metabolism最新文献

{"title":"Corrigendum to \"Desacetyl-alpha-melanocyte stimulating hormone and alpha-melanocyte stimulating hormone are required to regulate energy balance\" [Mol Metab 9 (2018) 207-216/29226825].","authors":"Kathleen G Mountjoy, Alexandre Caron, Kristina Hubbard, Avik Shome, Angus C Grey, Bo Sun, Sarah Bould, Martin Middlleditch, Beau Pontre, Ailsa McGregor, Paul W R Harris, Renata Kowalczky, Margaret A Brimble, Rikus Botha, Karen M L Tan, Sara J Piper, Christina Buchanan, Syann Lee, Anthony P Coll, Joel Elmquist","doi":"10.1016/j.molmet.2026.102380","DOIUrl":"https://doi.org/10.1016/j.molmet.2026.102380","url":null,"abstract":"","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102380"},"PeriodicalIF":6.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR75 Genetic Manipulations in Mice Reveal Central Mechanism for Weight Loss Independent of Developmental Effects.","authors":"Hua V Lin, Ibragim Gaidarov, Giuseppe Militello, Kevin W Hunt","doi":"10.1016/j.molmet.2026.102381","DOIUrl":"https://doi.org/10.1016/j.molmet.2026.102381","url":null,"abstract":"<p><strong>Objective: </strong>Human genetic studies have identified GPR75 loss-of-function variants to be strongly protective against obesity, establishing GPR75 as a compelling therapeutic target. However, critical questions remain regarding the translational potential of GPR75 inhibition. These include whether adult-onset inhibition can reverse established obesity and which tissue compartments mediate weight loss. Here, we address these fundamental questions using novel genetic mouse models.</p><p><strong>Methods: </strong>We generated whole-body inducible Gpr75 knockout mice to assess the effects of adult-onset Gpr75 deletion. Adult Gpr75flox/flox; R26-CreERT mice were treated with tamoxifen either pre-obesity and then challenged with high-fat diet (HFD) to evaluate protection from weight gain, or post-obesity establishment to evaluate weight loss. The role of brain Gpr75 was determined using neonatal intracerebroventricular injection of adeno-associated viruses carrying artificial microRNAs targeting Gpr75, and weight gain on HFD was evaluated. Both male and female mice were examined.</p><p><strong>Results: </strong>Adult-onset Gpr75 knockout prevented diet-induced obesity when induced prior to HFD challenge, indicating the body weight phenotype is independent of developmental effects. Strikingly, Gpr75 deletion induced in obese mice produced robust weight loss, demonstrating the potential for therapeutic efficacy. Body composition analysis revealed specific fat mass reduction with complete lean mass preservation in Gpr75 inducible knockout mice. The body weight differences occurred with no change or only modest reductions in food intake. Postnatal brain-targeted Gpr75 knockdown was sufficient to confer significant protection from diet-induced obesity, with efficacy correlating to knockdown efficiency.</p><p><strong>Conclusions: </strong>These data provide compelling genetic evidence that Gpr75 inhibition in adulthood can achieve substantial weight loss with selective fat mass reduction and lean mass preservation, operating through a mechanism that extends beyond appetite suppression alone. In addition, Gpr75 action in the postnatal brain plays a critical role in mediating these effects. Our findings de-risk a major translational concern, i.e., the developmental impacts of GPR75 on body weight regulation, and support the exploration of brain-penetrant GPR75 inhibitors as a novel obesity therapeutic strategy.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102381"},"PeriodicalIF":6.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased leptin signaling drives the response of hypothalamic LepRb neurons to diet-induced obesity.","authors":"James Dell'Orco, Warren Pan, Margaret B Allison, Abigail J Tomlinson, Jordan Wean, Paul V Sabatini, Christopher J Rhodes, David P Olson, Martin G Myers, Paulette B Goforth","doi":"10.1016/j.molmet.2026.102378","DOIUrl":"https://doi.org/10.1016/j.molmet.2026.102378","url":null,"abstract":"<p><p>The failure of hyperleptinemia to decrease adiposity in common forms of obesity has led to the notion that impaired leptin receptor (LepRb) signaling (\"leptin resistance\") might cause obesity. Because LepRb transcriptional signaling plays a central role in leptin action, we defined the control of gene expression in hypothalamic LepRb neurons in diet-induced obese (DIO) mice and in response to changes in circulating leptin. We found that LepRb neurons from DIO mice exhibited transcriptional changes similar to those induced by exogenous leptin. We also examined electrical activity in LepRb neurons from DIO mice, focusing on LepRb neurons in the ventromedial hypothalamic nucleus (VMN). This analysis revealed larger membrane depolarizations in response to current injection for VMN LepRb neurons from DIO mice. This effect was recapitulated by hyperleptinemia in vivo or exposure to elevated leptin ex vivo. Hence, hypothalamic LepRb neurons exhibit increased cellular leptin responses due to hyperleptinemia in DIO animals. These findings contradict the notion that impaired cellular leptin action underlies the development of DIO but rather suggest that increased leptin action drives DIO-associated changes in hypothalamic LepRb neuron function.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102378"},"PeriodicalIF":6.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of the E3 ubiquitin ligase MARCHF6 alters hepatic lipid metabolism and drives spontaneous hepatosteatosis.","authors":"Vinay Sachdev, Nienke M van Loon, Jenina Kingma, Roelof Ottenhoff, Josephine M E Tan, Marlene van den Berg, Suzanne Duijst, Aldo Jongejan, Johannes H M Levels, Patrick C N Rensen, Sander Kooijman, Jan-Freark de Boer, Folkert Kuipers, Katharina B Kuentzel, Dagmar Kratky, Yun Kwon, Anja Zeigerer, Sebastian Hendrix, Noam Zelcer","doi":"10.1016/j.molmet.2026.102379","DOIUrl":"10.1016/j.molmet.2026.102379","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, steatohepatitis (MASH), feature excessive hepatic fat accumulation, yet the relative contributions of dietary vs. endogenous fats and their interactions has remained enigmatic. Here, we identify the endoplasmic reticulum-associated E3 ubiquitin ligase MARCHF6 as a pivotal regulator of hepatic lipid metabolism. Global or hepatocyte-specific deletion of Marchf6 induced spontaneous accumulation of triglycerides and cholesteryl esters under chow-fed conditions, revealing a cell-autonomous hepatic defect independent of caloric excess. Loss of MARCHF6 stabilized its substrate squalene epoxidase (SQLE), enhancing sterol pathway flux while concomitantly activating the SREBP1-associated lipogenic transcriptional program and increasing lipoprotein clearance. Accordingly, lipidomic analyses demonstrated remodeling of the hepatic lipidome towards polyunsaturated, long-chain neutral lipids, consistent with increased lipogenesis-driven NADPH consumption. In line with this, pharmacological inhibition of the oxidative pentose phosphate pathway reduced lipid accumulation in MARCHF6-deficient human hepatocytes. Congruently, transcriptomic data from human MASLD/MASH patients revealed reduced hepatic MARCHF6 expression alongside an increase in that of the lipogenic genes SREBF1, FASN, and SCD1. Overall, these data establish MARCHF6 as a multifaceted gatekeeper that integrates sterol turnover, NADPH usage, and lipogenesis to maintain hepatic lipid homeostasis.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102379"},"PeriodicalIF":6.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal obesity remodels nutrient transport transcriptional programs in early mouse embryonic and extraembryonic cell lineages.","authors":"Amalia Caballero, Lijun Chi, Paul Delgado-Olguín","doi":"10.1016/j.molmet.2026.102375","DOIUrl":"10.1016/j.molmet.2026.102375","url":null,"abstract":"<p><p>Maternal obesity increases the risk of congenital anomalies and later-life metabolic disease in offspring. Still, underlying mechanisms remain unclear, particularly in extraembryonic lineages at the maternal-fetal interface, which remain poorly studied. We jointly profiled gene expression and chromatin accessibility in single nuclei from mouse embryos and extraembryonic tissues in a diet-induced obesity model at embryonic day 8.5, when multiple organogenesis programs are underway. This analysis generated an atlas of 36 cell lineages, including derivatives of all three germ layers and trophoblast populations. Lineage allocation was preserved in embryos from obese dams. However, transcription was widely dysregulated. Oxidative phosphorylation genes were broadly suppressed, and genes involved in hypoxia, cytoskeleton remodeling, and cell migration were enriched among upregulated pathways. Chromatin accessibility changed in a few lineages, most notably in extraembryonic visceral endoderm and parietal trophoblast giant cells. Differently accessible chromatin was enriched in binding motifs for retinoic acid receptors. Indeed, genes involved in retinol and lipoprotein transport were suppressed, and RNA in situ hybridization confirmed reduced expression of retinol transporters Ttr, Rbp4, and Stra6, and lipoprotein transporter Apoa1 in visceral yolk sac. Thus, obesity during pregnancy causes early transcriptional dysregulation that impairs retinoic acid and lipoprotein transport at the maternal-fetal interface, suggesting a mechanism through which maternal obesity could influence long-term developmental outcomes.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102375"},"PeriodicalIF":6.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variability in the leptin-melanocortin pathway and its role in weight loss.","authors":"Mariana Santos-Pereira, Marta Guimarães, Mariana P Monteiro, Sofia S Pereira, Luísa Azevedo","doi":"10.1016/j.molmet.2026.102377","DOIUrl":"10.1016/j.molmet.2026.102377","url":null,"abstract":"<p><p>Obesity is a multifactorial disease characterized by an excessive and abnormal accumulation of body fat that results from both genetic and environmental factors. In this review, we revisited the literature on the variability of obesity-associated genes and their impact on the effectiveness of obesity treatment interventions. Individuals harboring variants of these genes were found to have either better or worse outcomes after weight loss therapies. The majority of the genetic variants were identified in genes that play a role in the leptin-melanocortin pathway (LEPR, NPY, POMC, MC4R, GHRL, GHSR, GLP-1R, BDNF), which regulates food intake and energy expenditure. Both these processes are key elements for energy homeostasis, therefore relevant for the success/failure of weight loss strategies. Some genetic alterations were found to modulate the outcomes of different weight loss interventions, while others were only linked to the effectiveness of bariatric surgery, according to the studies here included and available. Herein, we revisited the most relevant molecular data, with a primarily focus on human studies, concerning how the genetic background influences the outcomes of weight loss interventions. Our aim is to gather relevant information on the genetic data related to weight loss strategies that can be compelling to guide clinical decisions, setting realistic expectations, and ultimately improving the long-term health conditions of individuals with obesity.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102377"},"PeriodicalIF":6.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A distinct vagus-beta cell neural circuit senses glucose and modulates insulin secretion.","authors":"Santosh Kumar, Young Jae Bahn, Claire Gao, Ji-Hyeon Lee, Audrey Noguchi, Valentina Baena, Zulfeqhar A Syed, Sungyoung Auh, Andrew Lutas, Michael J Krashes, Sushil G Rane","doi":"10.1016/j.molmet.2026.102371","DOIUrl":"10.1016/j.molmet.2026.102371","url":null,"abstract":"<p><strong>Objective: </strong>Vagal sensory neurons (VSN) convey peripheral glycemic information to the brain, yet the specific pathways that continuously sense glucose fluctuations and regulate hormone secretion and feeding remain poorly defined. Here, we examined the anatomical and functional aspects of an integrated circuit originating in pancreatic β-cells, projecting through the nodose ganglion, and engaging the dorsal vagal complex to relay feedback to β-cells.</p><p><strong>Methods: </strong>We performed monosynaptic viral fluorescent tracing, RNA sequencing, RNAscope, chemogenetics, optogenetics, neuronal silencing, automated glucose telemetry, feeding assays, neural activity measurements, glucose sensing, and intracellular calcium measurements using 2-photon microscopy.</p><p><strong>Results: </strong>The vagal transcriptome exhibited metabolic state- and diet-dependent regulation of pathways involved in glucose sensing, insulin secretion, and glucose homeostasis. Viral tracing identified abundant VSN innervating β-cells, including a subset expressing cocaine- and amphetamine-regulated transcript (VSN^CART), whose activity was modulated by metabolic state and altered brainstem neuronal activity. VSN^CART stimulation increased acetylcholine and C-peptide secretion and lowered blood glucose in a metabolic state-dependent manner, whereas silencing impaired glucose-stimulated insulin secretion and induced glucose intolerance. VSN^CART activation suppressed food intake, while inhibition increased feeding, also in a metabolic state-dependent manner. C-Fos labeling and two-photon Ca²⁺ imaging revealed that VSN^CART neurons exhibit dose-dependent excitatory responses to glucose.</p><p><strong>Conclusions: </strong>We identified a vagal sensory neuron-β-cell circuit and showed that VSN^CART neurons sense glucose to regulate insulin secretion, feeding behavior, and glucose homeostasis.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102371"},"PeriodicalIF":6.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems genetics reveals ITIH5 as a key mediator of adipocyte-Endothelial crosstalk.","authors":"Mingqi Zhou, Leandro M Velez, Danica Kwan, Lambda Moses, Casey D Johnson, Christy M Nguyen, Lillian Mott, Farah Gamie, Mona Fouladi, Hosung Bae, Amandine Verlande, Douglas Arneson, Paul Petrus, Miklós Péterfy, Andrea Hevener, Remi Buisson, Xia Yang, Lior Pachter, Aldons Jake Lusis, Selma Masri, Dequina A Nicholas, Cholsoon Jang, Ivan Marazzi, Marcus Seldin","doi":"10.1016/j.molmet.2026.102373","DOIUrl":"10.1016/j.molmet.2026.102373","url":null,"abstract":"<p><p>Proper adipose tissue homeostasis is essential for systemic metabolic health, and its disruption promotes insulin resistance, inflammation, and cardiometabolic risk. Using unbiased systems genetics analyses in mice and humans identified ITIH5 as a central regulator of adipose homeostasis and whole-body metabolism. Acute administration of recombinant ITIH5 with pan-organ sequencing revealed a local adipose function, suppressing recruitment of circulating immune cells. Consistently, ITIH5 treatment in human endothelial cells reduced leukocyte recruitment. We generated temporally controlled, adipocyte-specific ITIH5 overexpression models in mice, which improved adipose architecture, glucose metabolism under high-fat diet conditions, while consistently reducing left ventricular mass and cardiac output regardless of dietary group. Spatial transcriptomics of adipose tissue showed that elevated ITIH5 signaling to endothelia selectively impairs dendritic cell (DC) and B cell activation pathways. Collectively, these findings identify a mechanism whereby natural genetic variation in an adipocyte-secreted protein modulates endothelial-immune interactions in fat, influencing cardiometabolic homeostasis in a diet-dependent manner.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102373"},"PeriodicalIF":6.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleic acid fuels cisplatin-resistant ovarian cancer through FABP4-driven lipid uptake.","authors":"Ana Maria Isac, Andres Valdivia, Didi Zha, Yinu Wang, Vanessa Hernandez, Guangyuan Zhao, Chinmayee Vallabh Prabhu Dessai, Ujin Kim, Annapurna Sai Josyula, Wenan Qiang, Sandra Orsulic, Ji-Xin Cheng, Daniela Matei","doi":"10.1016/j.molmet.2026.102374","DOIUrl":"10.1016/j.molmet.2026.102374","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) depends on lipids as fuel for metastasis and growth. We previously showed that cisplatin resistant (Pt-R) OC cells uptake higher amounts of fatty acids (FAs) compared to sensitive (Pt-S) cells, a process which facilitates cancer cell survival under cisplatin-induced oxidative stress.</p><p><strong>Methods: </strong>Isogenic pairs of Pt-S and Pt-R OC cell lines were cultured in low serum conditions supplemented with either 50 μM oleic acid (OA, unsaturated) or 50 μM palmitic acid (PA, saturated) and used for viability assays, RNA-Sequencing, and cell cycle analysis. The effects of an OA enriched diet were assessed in intraperitoneal ovarian xenografts. The FABP inhibitor BMS-309403 was used to block lipid import in vitro and in vivo.</p><p><strong>Results: </strong>Pt-R cells were less viable than Pt-S cells under serum depletion and OA rescued starvation induced inhibition of cell proliferation, with more significant effects in Pt-R compared to Pt-S cells. RNA-sequencing showed that OA promoted upregulation of cell cycle-related pathways, including G2/M checkpoints, driven by the transcription factor E2F1. Supplementation with OA increased S- and G2/M phase cell populations in both Pt-S and Pt-R cells (p < 0.05) and E2F1 inhibition reduced OA-induced cell proliferation. An OA enriched diet promoted the growth and peritoneal dissemination of Pt-R ovarian xenografts. When co-cultured with adipocytes, Pt-R cells expressed higher levels of FA transporter proteins FABP4 and CD36 compared to sensitive cells and FABP4 expression was upregulated in paired metastatic and recurrent vs. primary human ovarian tumors (p < 0.05). An FABP inhibitor sensitized OC cells to cisplatin and suppressed the in vivo growth of Pt-R xenografts and patient derived xenografts.</p><p><strong>Conclusions: </strong>Pt-R OC cells harbor heightened dependence on unsaturated FAs compared to Pt-S cells and upregulate key transporters to increase FAs uptake. OA supports the proliferation of Pt-R cells in vitro and in vivo and a combination of carboplatin and FABP4 inhibitor reduces OC growth in vivo. These findings suggest that lipid composition may influence therapeutic response and raise important considerations for dietary guidance in patients with cancer.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102374"},"PeriodicalIF":6.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long non-coding RNA landscape of endurance exercise training.","authors":"Bernardo Bonilauri, Gregory R Smith, Archana N Raja, David Jimenez-Morales, Abdalla Ahmed, Christopher Jin, Lauren M Sparks, Martin J Walsh, Stephen B Montgomery, Sue C Bodine, Euan A Ashley, Maléne E Lindholm","doi":"10.1016/j.molmet.2026.102358","DOIUrl":"10.1016/j.molmet.2026.102358","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) regulate multiple cellular processes. However, knowledge of the responses and regulatory functions of lncRNAs in physical exercise and training remains limited. As part of the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we conducted a comprehensive analysis of lncRNA expression patterns in 18 tissues after an 8-week progressive endurance training program in rats. The lncRNA expression pattern was largely tissue-specific. In total, 759 unique lncRNAs were found to be differentially expressed across all tissues, generally displaying lower abundance, shorter transcript length, and reduced GC content compared with protein-coding genes. The most pronounced changes were observed in white and brown adipose tissues, the hypothalamus, and the adrenal gland. In the two skeletal muscle tissues investigated, only two lncRNAs were commonly differentially expressed. White and brown adipose tissues revealed a correlation between upregulated differentially expressed lncRNAs and coding genes associated with immune regulation. We identified substantial sex differences in the lncRNA regulatory landscape in response to exercise training. This comprehensive tissue-specific characterization of exercise-responsive lncRNAs opens new avenues for understanding exercise as molecular medicine and may inform the development of lncRNA-targeted therapeutics that harness the beneficial effects of exercise.</p>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":" ","pages":"102358"},"PeriodicalIF":6.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}