Physiological Reports最新文献

{"title":"Alterations in hippocampal somatostatin interneurons, GABAergic metabolism, and ASL perfusion in an aged male mouse model of POCD aggravated by sleep fragmentation.","authors":"Yun Li, Jiafeng Yu, Ningzhi Yang, Siwen Long, Yize Li, Lina Zhao, Yonghao Yu","doi":"10.14814/phy2.70153","DOIUrl":"10.14814/phy2.70153","url":null,"abstract":"<p><p>Sleep fragmentation (SF) is increasingly recognized as a contributing factor to postoperative cognitive dysfunction (POCD). Given the critical roles of somatostatin (SST) interneurons, associated gamma-aminobutyric acid (GABA)ergic neurotransmitters, and hippocampal perfusion in sleep-related cognition, this study examined changes in these mechanisms in preoperative SF affecting POCD induced by anesthesia/surgery in aged male mice. The Morris water maze (MWM), novel object recognition (NOR), and Y maze tests were utilized to evaluate POCD. Arterial spin labeling (ASL) was employed to measure hippocampal regional cerebral blood flow (rCBF). In vitro assays quantified the levels of GABAergic metabolites-such as SST, neuropeptide Y (NPY), glutamic acid decarboxylase 1 (GAD1), vesicular GABA transporter (VGAT), and GABA and the distribution of SST interneurons in the hippocampus through enzyme-linked immunosorbent assay and immunofluorescence. Preoperative 24-h SF exacerbated anesthesia/surgery-induced spatial memory impairments observed in the MWM, NOR, and Y maze tests. Preoperative 24-h SF significantly increased the number of SST interneurons in hippocampal CA1, elevated hippocampal levels of SST, NPY, GAD1, and GABA, and reduced the rCBF. Preoperative SF aggravated POCD in aged male mice, with an increased number of SST interneurons in hippocampal CA1, elevated hippocampal GABAergic metabolites, and a further reduction in rCBF.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70153"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute effect of exercise on appetite-related factors in males with obesity: A pilot study.","authors":"Sogand Asri, Farhad Rahmani-Nia, Payam Saidie, Timothy J Fairchild, Shahin Khodabandeh","doi":"10.14814/phy2.70167","DOIUrl":"10.14814/phy2.70167","url":null,"abstract":"<p><p>To investigate the role of appetite-related factors, including interleukin 6 (IL-6), irisin, interleukin 7 (IL-7), neuropeptide Y (NPY), and leptin, on appetite perception in males with obesity. Eleven males (BMI 35.3 ± 4.2 kg/m², V̇O_2peak 29 ± 3.1 mL/kg/min) participated in two experimental trials (MICE: 60 min of cycling at 60% of V̇O_2peak; CTRL: 60 min of quiet resting) using a crossover design. Appetite parameters, including IL-6, IL-7, irisin, and leptin, were measured. Additionally, appetite perception was assessed. IL-6 concentration increased significantly immediately post-exercise (95% CI: [2.207-12.192] pg/mL, p = 0.007) and remained elevated 1 hour post-exercise (95% CI: [2.326-11.855] pg/mL, p = 0.006) compared to CTRL. Irisin also rose significantly immediately post-exercise (95% CI: [0.084-3.061] ng/mL, p = 0.039). NPY decreased significantly 1 h post-exercise (95% CI: [(-20.601) - (-1.380)] ng/L, p = 0.027). No significant differences were observed for IL-7 (p = 0.748, <math> <semantics> <mrow><msubsup><mi>η</mi> <mi>p</mi> <mn>2</mn></msubsup> </mrow> <annotation>$$ {eta}_p^2 $$</annotation></semantics> </math> = 0.077) and leptin (p = 0.285, <math> <semantics> <mrow><msubsup><mi>η</mi> <mi>p</mi> <mn>2</mn></msubsup> <mo>=</mo> <mn>0.061</mn></mrow> <annotation>$$ {eta}_p^2=0.061 $$</annotation></semantics> </math> ). Appetite perceptions were suppressed immediately post-exercise (95% CI: [3.407-19.547] mm, p = 0.008) compared to CTRL. Sixty minutes of MICE increased IL-6 and irisin concentrations while suppressed NPY and appetite perceptions in males with obesity.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 24","pages":"e70167"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational hypercholanemia suppresses pregnancy-associated adipose mass increase and stimulates a pro-inflammatory environment in mice.","authors":"Vanya Nikolova, Alice L Mitchell, Elena Bellafante, Eugene Jansen, Georgia Papacleovoulou, Per-Olof Bergh, Hanns-Ulrich Marshall, Catherine Williamson","doi":"10.14814/phy2.70141","DOIUrl":"10.14814/phy2.70141","url":null,"abstract":"<p><p>Women with intrahepatic cholestasis of pregnancy (ICP) have hypercholanemia alongside an increased risk of dyslipidemia. We investigated how cholic acid (CA) supplementation in murine pregnancy impacts adipose tissue function. Mice were fed normal or 0.5% CA-supplemented chow from identification of copulatory plug until gestational day 14 or 15 (n = 10-11/group) and were matched experimentally with nonpregnant mice (n = 7/group). Tissue weights were measured alongside plasma bile acids, glucose, lipids, reactive oxygen metabolites (ROM), and adipokines. Subcutaneous and gonadal adipocyte mRNA expression was evaluated. CA supplementation inhibited pregnancy-associated adipose tissue expansion and decreased fetal weight. CA diet in pregnancy increased LDL-cholesterol and reduced HDL-cholesterol. Pregnancy and CA diet reduced lipid metabolism transcript expression in adipocytes. CA supplementation during pregnancy increased plasma ROM by 1.24-fold and suppressed inflammatory-modulating pentraxin-2/3 and insulin-like growth factor 1 (IGF-1) levels by >50% and >80%, respectively. Together, we show that hypercholanemia disturbs pregnancy-associated adipose tissue expansion and mRNA expression in late gestation concomitant with reduced IGF-1, altered lipid availability and increased inflammation and oxidation, which could impact fetal growth. This work highlights the need to better understand adipose tissue and redox stress changes in ICP pregnancies and the potential implications for fetal health.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70141"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olympic distance duathlon and cardiac performance in highly-trained triathletes.","authors":"J A Donaldson, J D Wiles, M Papadakis, S Sharma, R Sharma, J M O'Driscoll","doi":"10.14814/phy2.70154","DOIUrl":"10.14814/phy2.70154","url":null,"abstract":"<p><p>The effects of triathlon exercise on cardiac function are well documented. While Olympic triathlon (swim-bike-run) remains the standard format, increasing concerns about water quality in natural waterways present ongoing challenges for open-water swimming events, highlighting the potential need to consider alternative formats such as duathlon (run-bike-run) in some circumstances. An additional run may increase the overall metabolic and cardiovascular demand compared with the swim in triathlon, leading to reduced future performance. Conversely, the majority of EICF research reports reversal of post-exercise perturbations within 24-7 days of recovery but duathlon has not yet been studied in this context. Therefore, this study aimed to investigate the cardiac, autonomic, haemodynamic and biomarker responses during and following two Olympic distance (OD) duathlon separated by 7 days of recovery. Highly-trained (V O_2max >60 mL·kg^-1·min^-1) male participants (n = 10) completed two lab-based OD duathlons, either continuous (BD) or with functional measurements after each leg (UD), separated by 7 days of rest. Conventional echocardiography recorded standard and tissue Doppler measures of left ventricular (LV) structure and function. Speckle tracking echocardiography was used to measure global longitudinal strain (GLS). Time and frequency domain analysis of HRV, as well as plasma high sensitivity cardiac troponin T (hs-cTnT) were measured pre and post exercise. In the broken duathlon trial (BD) cardiac measurements and blood samples were also taken between each leg. In the unbroken duathlon (UD) participants performed each leg sequentially. Duathlon exercise resulted in similar cardiac functional and biomarker alterations as previously reported in triathlon and standalone running and cycling exercise. Cardiac troponins were still elevated following 24 h^-1 of recovery. However, functional changes were resolved within 24 h^-1 of passive recovery and did not impair subsequent duathlon performance, or pre-exercise measurements 7 days after the first trial. Whether or not elite or recreational athletes experience the same magnitude and reversibility of these changes remains to be elucidated further.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 24","pages":"e70154"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trim13-induced ubiquitination of RPS27A inhibits the progression of lung cancer by depending on the inactivation of NF-κB signaling pathway.","authors":"Lailing Li, Hui Zhou, Yayun Cui, Ke Xu","doi":"10.14814/phy2.70157","DOIUrl":"10.14814/phy2.70157","url":null,"abstract":"<p><p>Lung cancer (LC) is the leading cause of cancer-related death worldwide. Recent studies have shown that tripartite motif 13 (TRIM13) play important regulatory roles in the progression of different tumors. In this study, we focused on the role of TRIM13 in LC tumorigenesis and its underlying molecular mechanisms. The study demonstrated TRIM13 was identified as a novel tumor suppressor gene of LC and its overexpression suppressed LC progression in vitro and in vivo. Mechanistically, TRIM13 interacted with RPS27A, increasing RPS27A ubiquitination and degradation. Furthermore, RPS27A overexpression reversed the inhibitory effect of TRIM13 overexpression on LC progression. By binding to RPS27A and encouraging its ubiquitination and degradation, TRIM13 hindered LC advancement. We also found that RPS27A overexpression reversed the inhibitory effect of TRIM13 overexpression on NF-κB signaling, thereby further promoting the proliferation and metastasis of LC cell lines. Therefore, targeting the TRIM13/RPS27A/NF-κB signaling axis may be a promising target for LC treatment.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70157"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise during pregnancy modulates infant cellular and whole-body adiposity.","authors":"Alex Claiborne, Filip Jevtovic, Donghai Zheng, Cody Strom, Breanna Wisseman, Samantha McDonald, Edward Newton, Steven Mouro, James DeVente, Joseph A Houmard, Nicholas T Broskey, Linda E May","doi":"10.14814/phy2.70145","DOIUrl":"https://doi.org/10.14814/phy2.70145","url":null,"abstract":"<p><p>Non-pharmaceutical interventions are needed to target the growing intergenerational cycle of obesity. We aimed to determine whether in utero exposure to different exercise doses during pregnancy directly reduces infant cellular and whole-body adiposity. Pregnant women completed ~24 weeks of supervised exercise training; for standardization of exercise analysis (frequency, intensity, time, and volume-FIT-V), metrics were assessed from 16 to 36 weeks. Mesenchymal stem cells (MSC) collected from the umbilical cord at delivery underwent 21 days of adipogenic differentiation, then Oil Red O staining for lipid content. Infant body composition was measured at 1 month of age. ANCOVA and Pearson correlations determined the influence of prenatal exercise on infant adiposity. Exercise decreased infant MSC lipid content (p = 0.01) and body fat percentage (p = 0.009) irrespective of dose. Total exercise volume throughout pregnancy was negatively correlated with infant body fat % (R² = 0.31, p = 0.02) due to lower subscapular skinfolds (R² = 0.30, p = 0.02), while weekly exercise duration influenced adipogenic MSC lipid accumulation (R² = -0.23, p = 0.03) and BF% (R² = -0.15, p = 0.01). In utero exposure to exercise reduced cellular and whole-body infant adiposity in a dose-dependent manner.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70145"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrauterine fetal growth restriction in sheep leads to sexually dimorphic programming of Preadipocytes' differentiation potential.","authors":"Michell Goyal, Rosa I Luna Ramirez, Sean W Limesand, Ravi Goyal","doi":"10.14814/phy2.70143","DOIUrl":"10.14814/phy2.70143","url":null,"abstract":"<p><p>Fetal growth restriction (FGR) is a risk factor for obesity in adult life. Importantly, growth-restricted females are more prone to obesity than males. The mechanisms involved in this sexually dimorphic programming are not known. Previously, we have demonstrated that ambient hyperthermia (40°C) led to placental insufficiency and significant FGR, and the perirenal adipose tissue undergoes sexually dimorphic gene expression. We demonstrated that males undergo significant changes in gene expression with growth restriction. This was not the case in females. We have also demonstrated that the isolated preadipocytes from male FGR (MFGR) have reduced differentiation potential compared to control males & females and female FGR (FFGR). Thus, we hypothesized that growth restriction differentially programs gene expression and genetic pathways in perirenal preadipocytes, which reduces their differentiation potential in male fetuses in a sexually dimorphic manner. We created FGR by exposing pregnant sheep to ambient hyperthermia. After isolating preadipocytes from perirenal adipose tissue, we differentiated them following published protocols. We examined the gene expression before and after differentiation from control male, control female, MFGR, and FFGR female. We also compared our data with other published studies in mouse and human preadipocytes. Our results demonstrate that a set of 21 genes altered with preadipocyte differentiation to mature adipocytes is common in adipose tissue from both sexes, humans, mice, and sheep, at different organismal ages (embryonic, fetal, and adult) and different sites (subcutaneous inguinal, pancreatic, perirenal). We also demonstrate that female FFGR fetuses demonstrate all these 21 genes altered similar to control males and females; however, MFGR fetuses have six genes (Dgat2, Fabp4, Lipe, Lrrfip1, Spred3, and Thrsp) that are not changed with preadipocyte differentiation to mature adipocyte. These genes may be responsible for reduced differentiation potential and obesity in FGR males compared to FGR females. Another important finding of the present study is that Lrrfip1, known to be associated with obesity, was upregulated with FGR and requires further investigation. Overall, our studies provide several target genes that may play a crucial role in reducing the risk of MFGR for obesity.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70143"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eccentric exercise-induced muscle damage and inflammation in conjunction with high-altitude decompression in adults.","authors":"Frode Gottschalk, Mikael Gennser, Mattias Günther, Ola Eiken, Antonis Elia","doi":"10.14814/phy2.70147","DOIUrl":"10.14814/phy2.70147","url":null,"abstract":"<p><p>This study aimed to investigate the effect of eccentric exercise on exercise-induced muscle damage (EIMD) and inflammation on high-altitude-induced venous gas emboli (VGE). Subjects were exposed to an altitude of 24,000 ft. for 90 min, with either prior eccentric exercise (ECC) or no exercise (Control) 24 h before. Blood samples were collected at baseline (T₀), before (T₁), and after (T₂) altitude exposures. VGE load was evaluated using the Eftedal-Brubakk (ΕΒ) scale. Creatine kinase (CK) and myoglobin were used to assess muscle damage, while interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and fibrinogen were used to evaluate inflammation. ECC showed higher EB-scores during altitude exposures [median(range), 3(0-5)] than Control [1(0-4), p = 0.019]. Increases in myoglobin (+35%, p = 0.012), CK (+130%, p < 0.001), IL-6 (+72%, p = 0.02), and CRP (+63%, p = 0.004) were observed from T₀ to T₁ in ECC, but not Control. Significantly higher levels of myoglobin (p = 0.033), CK (p < 0.001), IL-6 (p = 0.016), and CRP (p = 0.002) were noted in the ECC compared to Control at T₁. IL-6 increased from T₁ to T₂ in ECC (p = 0.005), with higher levels than Control at T₂ (p = 0.046). A correlation was found between EB-scores and T₁ myoglobin levels (r_s = 0.450; p = 0.004), and to T₁-T₂ IL-6 changes (r_s = 0.396; p = 0.037). Eccentric EIMD followed by inflammation is associated with a higher decompression strain, with VGE load aggravating systemic inflammation.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70147"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-butylphthalide (NBP) ameliorated ischemia/reperfusion-induced skeletal muscle injury in male mice via activating Sirt1/Nrf2 signaling pathway.","authors":"Peng Lu, Wei-Peng Li, Ben-Jun Zhou, Wen-Ze Tian, Xiang Lu, Wei Gao","doi":"10.14814/phy2.70149","DOIUrl":"10.14814/phy2.70149","url":null,"abstract":"<p><p>N-butylphthalide (NBP) has been reported to have potential protective effects in ischemic stroke via its antioxidative properties. The present study was aimed to investigate the protective effects of NBP on ischemia/reperfusion (I/R)-induced skeletal muscle injury. Mouse model of I/R-induced skeletal muscle injury and hypoxia/reoxygenation (H/R)-induced C2C12 myotube injury model were constructed to test the protective effects of NBP both in vivo and in vitro. Our results showed that I/R resulted in skeletal muscle injury, as evidenced by elevated levels of LDH, CK, ROS, 3-NT, MDA, and 4-HNE as well as decreased activities of SOD, GSH-Px, and decreased expression of Myog and MyoD in gastrocnemius muscle, which was ameliorated by NBP treatment. Mechanistically, NBP treatment increased the expression of Sirt1 and Nrf2 in the injured skeletal muscle. Notably, the protective effects of NBP on I/R-induced skeletal muscle injury was diminished by the treatment of Sirt1 inhibitor. Further studies in H/R-induced C2C12 myotubes injury model also showed that NBP activated the Sirt1/Nrf2 pathway. NBP treatment upregulated the expression of myog and MyoD in H/R-stimulated C2C12 myotubes, which was eliminated by silencing of Sirt1. Taken together, our results suggest that NBP may alleviated I/R-induced skeletal muscle injury by activating Sirt1/Nrf2 signaling pathway.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70149"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivity-mediated molecular adaptations: Insights from a preclinical model of physical activity reduction.","authors":"Alice Meyer, Nicole Kim, Melissa Nguyen, Monica Misch, Kevin Marmo, Jacob Dowd, Christian Will, Milica Janosevic, Erin J Stephenson","doi":"10.14814/phy2.70140","DOIUrl":"10.14814/phy2.70140","url":null,"abstract":"<p><p>Insufficient physical activity is associated with increased relative risk of cardiometabolic disease and is an independent risk factor for mortality. Experimentally reducing physical activity rapidly induces insulin resistance, impairs glucose handling, and drives metabolic inflexibility. These adaptations manifest during the early stages of physical inactivity, even when energy balance is maintained, suggesting that inactivity-mediated metabolic reprogramming is an early event that precedes changes in body composition. To identify mechanisms that promote metabolic adaptations associated with physical inactivity, we developed a mouse model of physical activity reduction that permits the study of inactivity in animals prior to the onset of overt changes in body composition. Adult mice were randomized into three groups: an inactive control group (standard rodent housing), an active control group (treadmill running 5 d/week for 6-weeks), and an activity reduction group (treadmill running for 4-weeks, followed by 2-weeks of inactivity). Transcriptional profiling of gastrocnemius muscle identified seven transcripts uniquely altered by physical activity reduction compared to the inactive and active control groups. Most identified transcripts had reported functions linked to bioenergetic adaptation. Future studies will provide deeper characterization of the function(s) of each the identified transcripts while also determining how inactivity affects transcriptional regulation in other tissues.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 23","pages":"e70140"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}