Biology of Sex Differences最新文献

{"title":"Sex influences on tumor innervation.","authors":"Sarah M Barclay, Jeffrey Barr, Oduduabasi Isaiah, Mangalam Bajpai, Hailey Bullard, Ethan Neufeld, Craig C Welbon, Payal Ghosh, Destiny S Brockhaus, William C Spanos, Paola D Vermeer","doi":"10.1186/s13293-026-00887-9","DOIUrl":"10.1186/s13293-026-00887-9","url":null,"abstract":"<p><p>Peripheral solid malignancies are infiltrated by nerves. Using syngeneic cell lines, we set out to define whether sex influences tumor innervation in oral cancers and melanoma. Tumors grew significantly slower in females and were significantly more innervated than in males. In oral cancer, tumor-infiltrating nerves connect to a pre-existing neural circuit that enters the brain and impacts behavior. Thus, we evaluated the impact of sex on this circuit and assessed the behavioral consequences. We found no differences in the timing or extent of behavioral declines between oral tumor-bearing males and females. Moreover, in untreated mice, metastasis did not differ by sex. Treatment of oral tumors with cisplatin and radiation slowed tumor growth in male and female mice but significantly increased tumor innervation with females harboring the greatest innervation density. Treated females also harbored significantly increased metastases in their lungs compared to treated males. Treatment improved tumor-associated behavioral changes. While the tumor-brain circuit did not differ between males and females, the activation status of neurons and glia in projection areas significantly increased on the ipsilateral side. This heightened activation was attenuated following cisplatin/radiation treatment. These studies indicate that peripheral malignancies activate neurons and glia in central nervous system (CNS) projection areas, and that standard-of-care therapy attenuates this, which correlates with improved behavior. These findings emphasize that sex influences peripheral tumor-infiltrating nerves and brain function (via the tumor-brain circuit) and suggest that severing or silencing this circuit could improve patient outcomes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex- and age-dependent mitochondrial dysfunction and cognitive impairment in a mouse model of familial hypercholesterolemia.","authors":"Nathasha Prado-Lopes, Daniel Fagundes, Letícia Tavares, Whitney Santos, Wellinghton Barros, Henrique Moschen, Márcia Mortari, Jair Goulart, Angélica Amato, Jade de Oliveira, Paula Bellozi, Andreza Fabro de Bem","doi":"10.1186/s13293-026-00893-x","DOIUrl":"10.1186/s13293-026-00893-x","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism caused by loss-of-function variants in the low-density lipoprotein receptor (LDLR), resulting in persistently elevated LDL-cholesterol levels in plasma. Although hypercholesterolemia, especially the high levels of LDL, has been linked to an increased risk of dementia, the underlying mechanisms remain unclear. Here, we investigated the effects of sexual dimorphism and aging on metabolic and cognitive functions in a murine model of FH.</p><p><strong>Methods: </strong>Adult and middle-aged, male and female, C57BL/6 and LDLr^-/- mice were used in this study. Behavioral assessments included locomotor activity, spatial memory, and anxiety-like behavior. Plasma lipid profiles were measured, and mitochondrial function in the hippocampus and brown adipose tissue (BAT) was assessed using high-resolution respirometry.</p><p><strong>Results: </strong>LDLr^-/- mice of both sexes exhibited increased cholesterol and triglycerides levels. Male LDLr^-/- mice displayed hyperlocomotion in the Open Field (OF) and Elevated Plus Maze (EPM) at both ages, whereas this phenotype emerged in middle-aged female LDLr^-/- mice only in OF. Spatial memory impairments were observed in LDLr^-/- mice regardless of sex or age. Hippocampal oxygen consumption was reduced in adult males and middle-aged female mice, whereas BAT respiration was impaired in both sexes at middle-aged animals, affecting distinct respiratory parameters. Correlation analyses revealed that elevated cholesterol levels were associated with memory deficits and hyperlocomotion, along with positive correlations between hippocampal and BAT mitochondrial function.</p><p><strong>Conclusions: </strong>Collectively, these findings demonstrate that FH induces sex- and age-dependent alterations in behavior and mitochondrial metabolism, providing mechanistic insights into the link between FH and neurodegenerative disease risk.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transient sex-biased transcriptional program shapes early postnatal L2/3 neuron development.","authors":"Elia Marcos-Grañeda, Fernando Martín-Fernández, Linnea A Weiss, Juan C Oliveros, Marta Nieto","doi":"10.1186/s13293-026-00885-x","DOIUrl":"10.1186/s13293-026-00885-x","url":null,"abstract":"<p><p>Most neurodevelopmental disorders (NDDs), including intellectual disability, epilepsy, and autism spectrum disorder (ASD), exhibit marked sex differences in risk, incidence, prognosis, and clinical presentation. Increasing evidence suggests that these disorders often originate from alterations in circuit formation that occur during critical developmental windows preceding the onset of symptoms. However, the extent to which sexual dimorphism emerges during neuronal differentiation remains largely underexplored in the context of NDD research. In the cerebral cortex, layer (L) 2/3 excitatory pyramidal neurons, which integrate information across cortical areas and hemispheres, have been broadly implicated in NDDs. In this study, we investigate the transcriptional expression dynamics of L2/3 neurons across three developmental stages-embryonic day (E) 19, postnatal day (P) 4, and P7-and identify a window of transient, sex-biased gene expression at P4, possibly related to the process of brain masculinization. Furthermore, gene expression analysis following knockout (KO) mutations of Cux1 and Cux2 in L2/3 neurons reveals sex-biased dysregulation, with male neurons exhibiting heightened susceptibility and amplified transcriptional disruption, resulting in a molecular fingerprint that is distinct from their WT counterparts. These findings underscore the need to incorporate studies of sex-dependent differentiation trajectories as a biological variable in NDD research and may inform the development of more targeted, sex-specific therapeutic strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical thickness, surface area, and multisite pain: distinct patterns by sex in adolescence.","authors":"Esmeralda Hidalgo-Lopez, Christel Portengen, Tristin Smith, Hannah C Becker, Andrew Schrepf, Steven E Harte, Adriene M Beltz, Chelsea M Kaplan","doi":"10.1186/s13293-026-00898-6","DOIUrl":"10.1186/s13293-026-00898-6","url":null,"abstract":"<p><strong>Background: </strong>Multisite pain is common during adolescence and is influenced by sex-related neurobiological and developmental factors, but its developmental neural mechanisms are unclear.</p><p><strong>Methods: </strong>Utilizing data from the Adolescent Brain and Cognitive Development Study, we investigated the relation between cortical brain structure and multisite pain (assessed by youth self-reports of painful regions on a body map) in male (N = 3,299) and female (N = 2,844) adolescents aged 11-12 years. We focused on brain regions functionally linked to multisite pain (i.e., bilateral sensorimotor, cingulate, fronto-insular and inferior parietal cortex). We also explored the moderating role of pubertal status (assessed by the Pubertal Development Scale).</p><p><strong>Results: </strong>Findings revealed distinct brain structure-pain associations in male and female youth. Male youth exhibited an inverse linear relation between cortical thickness of the left pre- and postcentral gyri and number of pain sites. Female youth exhibited a non-linear relation between surface area of the right supramarginal gyrus and number of pain sites. Pubertal status moderated the cingulate cortical thickness-pain association in males; those in early puberty had an inverse relation between anterior and mid cingulate cortex thickness and pain sites, whereas this relation was positive in those beyond mid-puberty.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the sex-dependent neural organization linked to adolescent pain.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex shapes CD64 expression and vaccine-induced monocytic responses.","authors":"Charlotte Sophie Hansen, Julie Sellau, Anastasia Langanz, Leonie Marie Weskamm, Nele Wichern, Annika Bea, Johannes Brandi, Helena Fehling, Nils Groth, Melanie Lütkemeyer, Matthias Knödler, Henrik Nausch, Eirini Stivachti, Barbara Honecker, Hanna Lotter","doi":"10.1186/s13293-026-00897-7","DOIUrl":"10.1186/s13293-026-00897-7","url":null,"abstract":"<p><p>Sex-specific differences influence vaccine-induced immunity, with females generally mounting more robust immune responses than males. While enhanced antibody production in females is well established, the cellular mechanisms underlying these differences remain elusive. Monocytes and monocyte-derived dendritic cells contribute to vaccine-induced immunity by capturing antibody-antigen immune complexes via Fc gamma receptors (FcγRs), positioning them as potential mediators of sex-biased vaccine responses. Here, we investigated sex-specific differences in FcγRI (CD64)-expressing monocytic cells in humans and mice. Using flow cytometry, we demonstrate that healthy women display higher frequencies of CD64-positive monocytes and elevated CD64 expression in peripheral blood compared with men. In mice, a similar sex-specific pattern was consistently reproduced across diverse experimental settings, including in vitro and in vivo conditions. Functional in vitro assays revealed that classical monocytes from female mice mediated stronger classical antigen presentation to CD4⁺ T cells than male-derived monocytes in a CD64-dependent manner, as reflected by increased IFNγ production. In parallel, female-derived monocytes also displayed enhanced cross-presentation to CD8⁺ T cells; however, this effect occurred independently of CD64. Following intramuscular vaccination, flow cytometric analysis demonstrated that female mice exhibited increased frequencies of CD64-positive monocytes at the injection site, accompanied by higher CD64 surface expression levels on these cells. In addition, females showed significantly greater accumulation of monocytic cells in dorsal lymph nodes compared with males. Notably, castration of male mice enhanced monocytic recruitment to muscle tissue following immunization, indicating a role for sex hormones in regulating monocytic responses to vaccination. Together, these findings identify sex-specific regulation of CD64⁺ monocytic cells as a mechanism associated with enhanced antigen presentation in females and suggest that this pathway contributes to stronger vaccine-induced immune responses. In this context, our data underscore the relevance of biological sex in shaping Fcγ receptor-mediated immune mechanisms relevant to vaccination.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in dynamic and static measures of brain integration derived from resting-state functional magnetic resonance imaging.","authors":"Xiaojing Fang, Olivia Schwemmer, Abigail Hogan, Michael Marxen","doi":"10.1186/s13293-026-00891-z","DOIUrl":"10.1186/s13293-026-00891-z","url":null,"abstract":"<p><strong>Background: </strong>Understanding the impact of biological sex on the functional organization and dynamics of the brain is crucial for elucidating sex-specific differences in cognitive functions and neuropsychiatric disorders. Systems neuroscience often models the brain as a network of interconnected brain regions with functional connectivity (FC), i.e., the correlation between signal time courses, serving as a measure of connection strength. FC matrices, here derived from resting-state functional magnetic resonance imaging (rs-fMRI), define a network graph that can be characterized by its level of module segregation or, inversely, integration. Such parameters can be generated for the full length of the acquired data (static) or for short periods implying dynamically changing brain states. We recently made the interesting observation in a separate study (N = 63) that measures of brain integration and segregation based on dynamic functional connectivity (dFC) data differed between sexes, while graph-based measures based on static FC (sFC) did not, which we investigated in more detail in this study.</p><p><strong>Methods: </strong>We preregistered a replication of our analysis from the small sample in N = 501 subjects of the Human Connectome Project dataset. We performed cross-sectional comparisons between sexes of the static rs-fMRI graph parameters modularity and global efficiency, as well as the dFC parameters state prevalence, mean dwell time, mean inter-state transition time, and variability derived from a two-state model. Additionally, we explored whether sex differences in 66 cognitive and behavioral parameters are mediated by the FC integration measure with the strongest sex effect.</p><p><strong>Results: </strong>All static and dynamic measures of integration/segregation showed higher levels of functional integration in males, with effect sizes up to 0.60 for the dFC parameter prevalence. For three of the 66 explored cognitive and behavioral parameters, we observed that the prevalence of the integrated state mediated the sex difference: dexterity, agreeableness, and self-reported aggression.</p><p><strong>Conclusion: </strong>We found consistent evidence across two datasets that rs-fMRI-based measures of brain integration are increased in males. An exploratory analysis, which requires replication, suggests that such differences mediate personality differences. This study highlights that biological sex differences in brain functional organization may contribute to sex-typical behaviors.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences for clinical presentations and co-pathologies in four-repeat tauopathies.","authors":"Ece Bayram, Danelle J Carter, Sana Aslam, Emily Forbes, Samantha K Holden","doi":"10.1186/s13293-026-00899-5","DOIUrl":"10.1186/s13293-026-00899-5","url":null,"abstract":"<p><strong>Background: </strong>Four-repeat (4R)-tauopathies cause variable clinical profiles leading to clinical misdiagnosis. While sex differences are reported in Alzheimer's disease (AD), Lewy body disease (LBD), and clinically-defined frontotemporal dementia (FTD), little is known in 4R-tauopathies.</p><p><strong>Methods: </strong>National Alzheimer's Coordinating Center data were used for pathologically-defined 4R-tauopathies: progressive supranuclear palsy (PSP, n = 175), corticobasal degeneration (CBD, n = 114), argyrophilic grain disease (AGD, n = 230), Other-4R (n = 67). Sex differences for clinical presentation and co-pathologies were assessed adjusting for age and multiple comparisons.</p><p><strong>Results: </strong>Most common clinical diagnosis was PSP (41%) for PSP; unspecified FTD (36%) for CBD; AD for AGD (57%) and Other-4R groups (48%), without sex differences. Females had less cognitive decline, apathy, motor symptoms; were older at cognitive, behavioral change onset. Males were more likely to demonstrate LBD co-pathology and clinical profile.</p><p><strong>Conclusion: </strong>Both females and males have low clinical diagnostic accuracy for 4R-tauopathies. Females with 4R-tauopathies may experience less severe clinical presentations and less co-pathology.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related differences in Huntington's disease: a scoping review.","authors":"Greta Hemicker, Katarína Schwarzová, Clancy Cerejo, Samuel Labrecque, Marina Peball, Federico Carbone, Bernadette Wimmer, Atbin Djamshidian, Klaus Seppi, Beatrice Heim","doi":"10.1186/s13293-026-00895-9","DOIUrl":"10.1186/s13293-026-00895-9","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder and emerging evidence indicates sex-specific differences in disease manifestation and progression.</p><p><strong>Objective: </strong>To summarize current evidence on sex-related differences in HD across genetic, clinical, biomarker, and treatment domains and identify gaps in knowledge.</p><p><strong>Methods: </strong>A literature search was performed in PubMed and Google Scholar (up to 31.01.2026). Eligible studies examined sex- or gender-related differences in individuals with genetically confirmed HD or those at risk. Meta-analyses, reviews, animal studies, theses, abstracts only, and non-English papers were excluded. After screening and full-text review, secondary citation tracking identified further studies. Sex was defined as the biological classification of participants (male/female) as originally reported, whereas gender was defined as socially constructed roles or identities, where explicitly assessed. Terminology in this review reflects the terminology used in the original publications.</p><p><strong>Results: </strong>Fourty-four studies met inclusion criteria. Genetic studies showed similar cytosine-adenine-guanine (CAG) repeat lengths across sexes when parent-of-origin was not considered, while paternal transmission was consistently linked to repeat expansion and earlier disease onset. Clinically, women more frequently exhibited depression, irritability, and greater functional impairment, whereas men more often showed apathy and substance misuse. Medication patterns differed, with women being more likely to receive antidepressants and anxiolytics, and men antipsychotics. Biomarker studies indicated potential sex-related differences in body composition, uric acid, neuroimaging, and hormonal profiles, though available evidence remained heterogeneous and exploratory.</p><p><strong>Conclusions: </strong>Sex-related differences in HD are evident in genetic transmission, psychiatric symptoms, functional decline, and medication use. Biomarker findings suggest additional sex-specific biological signatures.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No impact of sex or testosterone treatment on wheel running in a rat model of inflammatory bowel disease.","authors":"Rebecca M Craft, Christyne M Sewell, Christa M Hickey, Kristen Delevich, Michael M Morgan","doi":"10.1186/s13293-026-00882-0","DOIUrl":"10.1186/s13293-026-00882-0","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in inflammatory bowel disease (IBD) have been reported in humans, and gonadal steroid hormones are implicated in these sex differences. Although pain is a primary complaint among IBD patients, and pain often does not correlate with colon pathology, most animal studies focus on physiological rather than behavioral measures of IBD severity. Thus, the present study determined whether the impact of colitis on global measures of well-being is greater in female than male rats, and whether testosterone ameliorates this impact in females.</p><p><strong>Methods: </strong>Blank capsules were implanted into gonadally intact adult females and males, and another group of females was implanted with testosterone-filled capsules. Three weeks later, trinitrobenzene sulphonic acid (TNBS) was administered intracolonically to induce colitis. Body weight and continuous, home cage wheel running were measured daily, before and for 10 days after colitis induction. Estrous cycle was monitored for 21 days in a subset of females. At the end of the study, serum testosterone and estradiol were determined, in addition to clitoral/preputial gland size.</p><p><strong>Results: </strong>TNBS suppressed body weight and wheel running, which partially recovered within 10 days, with no group differences in magnitude or time course of these effects. Serum testosterone was elevated in testosterone-treated compared to control females and did not differ significantly from males, whereas serum estradiol was similar across groups. Testosterone suppressed females' estrous cycling and increased clitoral gland size. At the end of the study, serum estradiol was found to be correlated with suppression of body weight and wheel running during the previous 10 days.</p><p><strong>Conclusions: </strong>These results do not support the hypothesis of sex differences in well-being after IBD induction, or that testosterone ameliorates IBD effects in females, but corroborate human and rodent data suggesting that estradiol is associated with IBD severity in both sexes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in response to a short-term training program intervention in obese adolescents: a plasma metabolomics study.","authors":"Lin Zhu, Xianyan Xie, Huiguo Wang, Zekai Chen","doi":"10.1186/s13293-026-00896-8","DOIUrl":"10.1186/s13293-026-00896-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;This study aims to investigate sex differences in the response to short-term Training Program intervention and the underlying metabolomic mechanisms among obese adolescents.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 98 obese adolescents underwent a 4-week, strictly controlled short-term Training Program intervention. Pre- and post-intervention measurements included body morphometry, body composition, lipid metabolism, and glucose homeostasis indicators. Plasma samples were analyzed using targeted metabolomics. Linear mixed-effects models (LMM) were employed to identify Sex-differential Responsive Metabolites, with volcano plots utilized to visualize metabolic regulation preferences between sexes. Hierarchical clustering analysis identified co-regulated metabolic modules within the Sex-differential Responsive Metabolites for pathway analysis. Partial least squares (PLS) regression models were constructed separately for males and females to identify metabolic biomarkers capable of predicting changes in clinical indicators.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Post-intervention, both males and females showed significant decreases in weight, body mass index (BMI), chest circumference, waist circumference, hip circumference, waist-to-hip ratio, body water, Body fat mass, fat free mass, skeletal muscle mass, body fat percentage, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (P &lt; 0.001). Additionally, HOMA-β levels significantly decreased only in females (P = 0.01). After adjusting for developmental maturity and baseline metabolic risk, the improvements in body fat mass and body fat percentage in males were significantly greater than those in females (both P &lt; 0.01), whereas no statistical differences were found in weight and BMI improvements (P &gt; 0.05). The change in HOMA-β differed significantly between sexes (P = 0.031), with females exhibiting a more pronounced downregulation following the intervention. LMM identified 65 Sex-differential Responsive Metabolites. Hierarchical clustering revealed two co-regulated modules: Module 1 showed a strong upward trend in males but a weak response in females, significantly enriched in the linoleic acid metabolism pathway; Module 2 showed a downward trend in both sexes, but the magnitude of downregulation was more pronounced in males, significantly enriched in pathways related to amino acid catabolism and energy metabolism. PLS model analysis indicated that Sex-differential Responsive Metabolites had predictive capacity for male Fasting Blood Glucose (FBG, R&lt;sup&gt;2&lt;/sup&gt;Y = 0.2653,Q&lt;sup&gt;2&lt;/sup&gt; = 0.0091), female FBG (R&lt;sup&gt;2&lt;/sup&gt;Y = 0.3552,Q&lt;sup&gt;2&lt;/sup&gt; = 0.1321), and female LDL-c (R&lt;sup&gt;2&lt;/sup&gt;Y = 0.3895,Q&lt;sup&gt;2&lt;/sup&gt; = 0.1853).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Obese adolescents exhibit significant sexual dimorphism in their response to short-term Training Program. Under the same standardized training program, males achieve greater fat ","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}