Biology of Sex Differences最新文献

{"title":"Sex-based associations between neighborhood disadvantage and brain-gut alterations in individuals with irritable bowel syndrome.","authors":"Lisa A Kilpatrick, Lin Chang, Jennifer S Labus, Andrea S Shin, Michelle Choy, Tien S Dong, Bruce Naliboff, Emeran A Mayer, Arpana Church","doi":"10.1186/s13293-025-00739-y","DOIUrl":"10.1186/s13293-025-00739-y","url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome (IBS) is a stress-sensitive disorder that exhibits sex differences in brain-gut-microbiome interactions. Neighborhood disadvantage is a chronic stressor that may influence brain-gut-microbiome health in patients with IBS, potentially contributing to clinical profiles in a sex-specific manner. This study evaluated sex-based associations between neighborhood disadvantage and clinical characteristics, cortical morphology, and Prevotella relative abundance (a sex-specific microbial marker in IBS) in individuals with IBS compared to healthy controls (HCs).</p><p><strong>Methods: </strong>Brain magnetic resonance imaging scans were obtained in 182 individuals with IBS (age, 31.0 ± 0.8 years; 128 females) and 161 HCs (age, 32.7 ± 1.0 years; 94 females). Fecal microbiome data was available in 113 IBS participants (80 females) and 127 HCs (74 females). Current neighborhood disadvantage was assessed as the Area Deprivation Index (ADI), with ADI⩾5 defined as high ADI. Group differences in the associations of high ADI with symptoms, Prevotella, and cortical morphology were evaluated using partial least squares.</p><p><strong>Results: </strong>Diagnosis Differences: High ADI was associated with greater lateral intraparietal surface area in IBS vs HCs. Sex Differences: There were greater negative associations between high ADI and surface area in frontal operculum and thickness in frontopolar and primary somatosensory regions in females vs males. Diagnosis*Sex Differences: There were greater negative associations between high ADI and surface area in superior parietal and sensorimotor regions in IBS females vs males, and greater negative associations between high ADI and surface area and thickness in dorsolateral prefrontal and parietal regions, respectively, in IBS males vs females. High ADI was associated with greater symptom severity in IBS males, greater perceived stress in both IBS and HC females, and Prevotella relative abundance in IBS females (all p's < 0.01).</p><p><strong>Conclusions: </strong>Neighborhood disadvantage is associated with greater symptom severity in IBS males and both higher perceived stress (exacerbates symptoms) and Prevotella abundance (protective) in IBS females. It generally has a greater negative impact on emotion/pain-related cortical morphology in females vs males. However, there are more prominent somatosensory reductions in IBS females, and prefrontal reductions in IBS males. These findings highlight the interplay between social and biological factors in IBS and underscore the need for targeted, sex-specific interventions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"61"},"PeriodicalIF":5.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820382","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-dependent epigenetic disruption of YY1 binding by prenatal BPA exposure downregulates Matr3 and alters Agap1 splicing in the offspring hippocampus.","authors":"Pattanachat Lertpeerapan, Songphon Kanlayaprasit, Surangrat Thongkorn, Kasidit Kasitipradit, Pawinee Panjabud, Kwanjira Songsritaya, Thanawin Jantheang, Masanobu Morita, Takaaki Akaike, Valerie W Hu, Depicha Jindatip, Thanit Saeliw, Tewarit Sarachana","doi":"10.1186/s13293-025-00744-1","DOIUrl":"10.1186/s13293-025-00744-1","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"63"},"PeriodicalIF":5.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820383","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 the relationship between pain and autonomic outflow during a cold pressor test.","authors":"Laila A Chaudhry, Yasmine Coovadia, Brittany K Schwende, Danielle E Berbrier, Will Huckins, Jinan Saboune, Derek A Skolnik, Emily K Van Berkel, Jeffrey S Mogil, Charlotte W Usselman","doi":"10.1186/s13293-025-00743-2","DOIUrl":"10.1186/s13293-025-00743-2","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is partly maintained by the sympathetic nervous system, whose activity is best measured by muscle sympathetic nerve activity (MSNA). MSNA responses to acute pain have been thoroughly investigated, whereas MSNA responses to longer-lasting pain are poorly understood. Therefore, this study examined the relationship between pain ratings and peroneal MSNA during a tonic cold pressor test (CPT) in male and female participants.</p><p><strong>Methods: </strong>We obtained MSNA measures during a 6 min CPT in 18 young adult (20-33 years) men and women. Verbal pain ratings (0-10) and autonomic outcomes (heart rate [HR], mean arterial blood pressure [MAP], and MSNA) were assessed simultaneously at multiple time points across the CPT.</p><p><strong>Results: </strong>Pain, HR, and MAP increased in the initial 30s in both sexes. Females increased their MSNA burst frequency (BF) to a greater extent than males. Across the full CPT we observed a positive relationship between pain and HR in males, a positive relationship between pain and MSNA BF in females, and a negative relationship between pain and MSNA burst amplitude in females.</p><p><strong>Conclusions: </strong>Overall, males displayed a strong relationship between tonic pain and HR, an index of parasympathetic activity, whereas females displayed strong and offsetting relationships between tonic pain and purely sympathetic MSNA variables. These observations suggest sex differences in autonomic mechanisms during tonic pain, which may have relevance to ongoing efforts to modulate pain via manipulations of the autonomic nervous system, as well as sex/gender disparities in chronic pain prevalence.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"60"},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793384","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":"Lack of glutamate neurotransmission in melanin-concentrating hormone neurons alters mouse reproduction and metabolism in a sex-specific manner.","authors":"Bethany G Beekly, Dania Zeidan, Wenicios F Chaves, Jonah-Isabella Sta-Monica, Thomas Saunders, Cristina Saenz de Miera, Christian R Burgess, Carol F Elias","doi":"10.1186/s13293-025-00742-3","DOIUrl":"10.1186/s13293-025-00742-3","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"59"},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793383","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 structural and receptor mRNA expression in the ventral anterior cingulate cortex and a potential role of perineuronal nets in monogamous pair bond establishment (Peromyscus californicus).","authors":"Candice L Malone, Jiaxuan Li, Elsa M Luebke, Leykza Carreras-Simons, Warren W Treis, Emma R Hammond, Patrick K Monari, Catherine A Marler","doi":"10.1186/s13293-025-00741-4","DOIUrl":"10.1186/s13293-025-00741-4","url":null,"abstract":"<p><p>The monogamous California mouse (Peromyscus californicus) exhibits distinct behavioral changes during pair bond formation. Using a detailed temporal behavioral analysis over seven days, we found a rapid decrease in aggression within 24 h of pair introduction in this highly territorial species. After this aggression reduction, the gradual increase in affiliative behaviors varied by type of affiliative behavior and ranged from one to seven days. We then measured neurobiological changes at three time points during this transition to uncover mechanisms that might govern this shift from aggressive to affiliative behavior, revealing novel sex differences that add to current research on biological mechanisms of social bonding. Specifically, we examined plasticity through mRNA expression of two perineuronal net (PNN) associated proteins, HAPLN and ACAN, in two brain regions implicated in affiliation, aggression, and social cognition: the ventral anterior cingulate cortex (vACC) and lateral septum (LS). The vACC in females exhibited higher expression levels of both of these PNN components relative to males. Additionally, we observed a decrease in ACAN mRNA expression in the vACC over the course of pair bond establishment, but no such change in the LS. Furthermore, oxytocin receptor (OXTR) and vasopressin receptor (AVPR) plasticity exhibited sex-specific patterns in the vACC during pair bond formation. Females displayed higher OXTR mRNA expression across the bonding period, whereas males expressed higher AVPR mRNA levels. We discuss how a decrease in PNNs could allow for an increase in receptor plasticity in the vACC as the pair bond is established. Moreover, we suggest that structural plasticity across this social transition may differ between males and females due to factors such as pre-pair sociality and aggression/territoriality changes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"58"},"PeriodicalIF":5.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783396","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 comparison of social drivers of health identification and intervention rates by sex among patients receiving primary care.","authors":"Leah A Holcomb, Elizabeth Crabtree Killen, Kelsey R Ryan, Aimee L McRae-Clark, Stacey Seipel, Rita Aidoo, Constance Guille","doi":"10.1186/s13293-025-00738-z","DOIUrl":"10.1186/s13293-025-00738-z","url":null,"abstract":"<p><strong>Background: </strong>Social drivers of health (SDOH) significantly influence health behaviors and outcomes, yet sex-based disparities in these domains remain underexplored. Identifying these differences is essential for guiding equitable, evidence-based interventions.</p><p><strong>Methods: </strong>We analyzed electronic health record (EHR) data from all patients with a documented male or female sex who had a primary care visit or inpatient stay at the Medical University of South Carolina (MUSC) between January 1, 2023, and December 31, 2024 (n = 493,920). SDOH screening responses were categorized as \"affirmative\" (at risk) or \"negative\" (not at risk) across 17 predefined domains using Epic's logic-based risk classification. Descriptive statistics were calculated, and z-tests for proportions were used to assess sex-based differences. Race and ethnicity were included as descriptive variables; no inferential tests by race/ethnicity were conducted.</p><p><strong>Results: </strong>Females were significantly more likely to report financial strain (7.96%), food insecurity (4.44%), housing instability (3.72%), intimate partner violence (2.03%), transportation barriers (2.20%), depression (3.93%), and stress (14.10%). Despite these risks, females also reported higher rates of protective behaviors such as physical activity (74.2%) and social connectedness (14.22%). In contrast, males had higher rates of alcohol use (4.67%), tobacco use (35.6%), and adolescent substance use (2.14%). Notably, White/Caucasian males reported the highest alcohol use (6.23%), and both White and Black males reported the highest tobacco use (42%).</p><p><strong>Conclusions: </strong>Sex-based disparities in SDOH reflect broader structural and social inequities. Health systems should implement routine, EHR-integrated SDOH screening and use this data to inform tailored, gender-responsive interventions-such as increasing access to mental health support for women and addressing substance use among men-while also considering how intersecting factors like race, income, and caregiving burden compound these risks.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"57"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717304","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 the impact of social determinants of health on substance use disorder treatment outcomes.","authors":"C Leonardo Jimenez Chavez, MacKenzie R Peltier, Sherry A McKee","doi":"10.1186/s13293-025-00734-3","DOIUrl":"10.1186/s13293-025-00734-3","url":null,"abstract":"<p><strong>Background: </strong>Social determinants of health (SDOH) and clinical severity factors are known to shape substance use disorder (SUD) treatment outcomes, yet limited research has explored how these influences differ by sex. Understanding these differences is important to improving treatment equity and outcomes in publicly funded treatment systems.</p><p><strong>Methods: </strong>This study analyzed data from the 2018-2022 Treatment Episode Data Set-Discharges (TEDS-D), a national dataset of adults discharged from publicly funded SUD treatment programs. Sex-stratified binary logistic regressions were used to examine predictors of two outcomes: treatment non-completion and substance use at discharge. Predictors included SDOH (i.e., employment, education level, housing status, criminal justice involvement, prior treatment history, marital status, health insurance coverage and treatment duration) and indicators of SUD severity (e.g., age at first use, polysubstance use, and co-occurring psychiatric disorders).</p><p><strong>Results: </strong>Both SDOH and clinical severity indicators were significantly associated with poorer treatment outcomes, with distinct patterns by sex. Women showed more consistent risk for poor treatment outcomes across predictors, including unemployment, psychiatric comorbidities, and polysubstance use, while lack of prior treatment history was the strongest predictor of substance use at discharge and dropout for men. Other predictors, such as housing instability, criminal justice involvement, and later-onset substance use, were also associated with increased risk of non-abstinence and dropout, with notable sex differences. Health insurance coverage was associated with better outcomes for both sexes, with the protective effect more consistent in women.</p><p><strong>Conclusions: </strong>These findings emphasize the need for sex-informed treatment approaches that address both social determinants of health and clinical complexity. Tailoring care to the unique risks and contexts of men and women may improve retention and reduce substance use at discharge, particularly in publicly funded systems. Highlights We examined social determinants of health (SDOH), and substance use disorder (SUD) severity-related predictors of substance use and treatment completion in a national sample of approximately 7 million adults. Women demonstrated more consistent vulnerability across predictors, including unemployment, co-occurring psychiatric disorders, and polysubstance use. For men, lack of prior treatment for SUD was the most consistent predictor for substance use at discharge and treatment dropout. Housing instability, access to healthcare, and financial barriers showed sex-specific effects, with women generally experiencing great risk of unsuccessful treatment. Findings highlight the importance of improving SUD care to address sex-specific risks and structural barriers, especially in publicly funded systems. Plain English Summa","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"56"},"PeriodicalIF":5.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688829","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":"Sulcal pits as potential markers of early sex-related human brain differences in healthy adults.","authors":"Noemí Hostalet, Pilar Salgado-Pineda, Yasser Alemán-Gómez, Lluís Cobos-Aumatell, Alejandro Sotero-Moreno, Irene París-Gómez, Ana Aquino-Servín, Erick J Canales-Rodríguez, Amalia Guerrero-Pedraza, Salvador Sarró, Jordi Ortiz-Gil, Kiho Im, Neus Martínez-Abadías, Edith Pomarol-Clotet, Mar Fatjó-Vilas","doi":"10.1186/s13293-025-00733-4","DOIUrl":"10.1186/s13293-025-00733-4","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"55"},"PeriodicalIF":5.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688830","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":"Electrocardiographic sex index: a continuous representation of sex.","authors":"Ibrahim Karabayir, Turgay Celik, Luke Patterson, Liam Butler, David Herrington, Oguz Akbilgic","doi":"10.1186/s13293-025-00727-2","DOIUrl":"10.1186/s13293-025-00727-2","url":null,"abstract":"<p><p>Clinical risk calculators consider sex as a binary variable. However, sex is a complex trait with anatomic, physiologic, and metabolic attributes that are not easily summarized in this manner [1]. We propose a continuous representation of sex, the ECG Sex Index (ESI), derived via artificial intelligence analyses of electrocardiograms (ECG-AI).We used an ECG repository at Wake Forest Baptist Health (Winston-Salem, NC) to develop a convolutional neural network-based ECG-AI model to detect sex from standard 12-lead ECGs. We utilized a rank-ordered transformation of the outcomes of ECG-AI to create the ESI. We also created a sex discordance index (SDI) from the ESI and assessed its utility in 1-year risk prediction for all-cause mortality, heart failure, and kidney failure.The Wake Forest cohort included 3,573,844 ECGs and electronic health record data from 754,761 patients; 75% were White, 17% were Black, and 51% were female, with a mean age (SD) of 61 (17) years. The PhysioNet external validation cohort included 45,152 ECGs from 10,646 patients from two hospitals in China. The PhysioNet cohort was 100% Asian, 43.6% female, and had a mean age (SD) of 59 (20) years. ECG-AI provided a holdout area under the curve of 0.95 and an external validation area under the curve of 0.92. Lower ESI scores in males and higher ESI scores in females were associated with a greater risk for clinical outcomes. The ESI and SDI demonstrated comparable accuracy to binary sex in logistic regression analyses and outperformed binary sex in predicting clinical outcomes, highlighting their value as predictors in risk calculators for all-cause mortality, heart failure, and kidney failure.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"53"},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658205","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-specific changes in energy demand during the preplaque stage in a transgenic Alzheimer's mouse model.","authors":"Rongwan Sun, Leonie-Kim Zimbalski, Stefanie Schreyer, David Baidoe-Ansah, Aida Harutyunyan, Arnd Heuser, Rachel N Lippert, Joachim Spranger, Knut Mai, Sebastian Brachs","doi":"10.1186/s13293-025-00737-0","DOIUrl":"10.1186/s13293-025-00737-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cognitive deficits and brain glucose hypometabolism, lipid peroxidation and mitochondrial dysfunction are early pathological events in murine models and patients with Alzheimer's disease (AD). Data from our previous research indicate that transgenic mice of the APP23 line, a murine AD model, exhibited higher energy expenditure and mitochondrial dysregulation in the liver as early as 3 months of age, which is considered the preplaque stage. Since women have a higher risk and mortality rate for AD, with potential sex-specific confounders as longevity, biological, genetic, and social factors also needing to be considered, sex differences in energy metabolism in AD remain insufficiently investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Here, we investigated sex-specific differences in mitochondrial respiration and metabolic profiles of 3-4-month-old, preplaque APP23 transgenic mice, in which we did not detect inflammatory signals and pathological amyloid-beta (Aß) plaques in brain or liver. Their mitochondrial respiration was assessed measuring oxygen consumption rates in isolated primary hepatocytes, stromal vascular cells (SVCs) and re-differentiated adipocytes. Furthermore, we analyzed energy balance, including food intake, locomotor activity, energy expenditure and fecal calorie loss.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We observed an upregulation of hepatic mitochondrial respiration in preplaque APP23 females. Female-derived SVCs and differentiated adipocytes improved mitochondrial flexibility with palmitate loading in vitro, which was in line with decreased plasma triglycerides in preplaque APP23 females in vivo. However, no differences in mitochondrial respiration were detected in hepatocytes and re-differentiated adipocytes derived from male APP23 mice. Furthermore, we corroborated an increased mortality during the preplaque stage, particularly in females, which exhibited reduced hyperactivity and caloric intake before death compared to survivors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our data demonstrate that preplaque APP23 female mice have disequilibrated mitochondrial oxidation in hepatocytes and adipocytes as well as higher energy expenditure due to increased activity before AD manifestation. In contrast, male APP23 mice did not exhibit such metabolic changes. Constant excessive energy loss and limited calorie supply potentially contribute to the higher risk of mortality, especially in APP23 females during young adulthood. Alzheimer's disease (AD) affects men and women differently, with women at higher risk and mortality. This study explored sex differences in energy metabolism using APP23 transgenic mice, a model of AD, at young age (3-4 months) - before pathological amyloid-beta (Aß) plaques develop in the brain and liver. Female APP23 mice showed increased mitochondrial activity in liver and fat cells, higher energy expenditure, and more movement while eating less. They also excreted more energy in their feces. N","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"54"},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658206","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}