Frontiers in Physiology最新文献

{"title":"Aerobic exercise ameliorates atherosclerosis-induced cognitive impairment via hippocampal IL-33/NF-κB signaling modulation.","authors":"Jianwei Peng, Zaoshang Chang, Jinyun Wang, Zijie Liao, Yunjie Yang, Lianwei Mu, Shen Wang, Junhao Huang, Jingbo Xia, Min Hu","doi":"10.3389/fphys.2025.1608268","DOIUrl":"10.3389/fphys.2025.1608268","url":null,"abstract":"<p><p>Atherosclerosis (AS), a common cardiovascular condition, is often linked to cognitive dysfunction. This study investigates how aerobic exercise affects cognitive impairments caused by AS in ApoE^-/- mice. At 8 weeks old, male ApoE^-/- mice were fed a high-fat, high-cholesterol diet (HFHCD) for 6 weeks to induce AS, with C57BL/6J mice on a standard diet as control group (WT). Initially, the study compared aortic plaque and cognitive performance between the WT and AS mice. Then, AS mice were divided into sedentary (AS-SED) and exercise (AS-EX) groups for a 10-week aerobic exercise intervention. Results showed significant aortic plaques and cognitive deficits in AS mice after 6 weeks on the HFHCD diet. However, the 10-week exercise reduced plaque, improved cognition, and enhanced cerebral blood flow. Exercise intervention also decreased IL-33 expression in the hippocampus and inhibited NF-κB and IκBα phosphorylation. Furthermore, aerobic exercise reduces M1 microglial activation and pro-inflammatory cytokines like IL-6, TNF-α, and IL-1β in the hippocampus of AS mice, thereby decreasing neuroinflammation. In summary, aerobic exercise can effectively improve cognitive function by decreasing IL-33 expression and inhibiting NF-κB activation, which in turn reduces microglial activation and the release of inflammatory mediators in the hippocampus. This study provides evidence for aerobic exercise to improve cognitive impairment caused by AS.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1608268"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth performance and gut health of broilers fed heat- and enzyme-treated <i>Vigna unguiculata</i> and <i>Cajanus cajan</i> diets.","authors":"Filomena Dos Anjos, Julia Dibner, Frances Yan, Mercedes Vazquez-Anon, Ellen S Dierenfeld, Abilio P Changule, Manuel Garcia-Herreros, Custódio G Bila, Michael Chimonyo","doi":"10.3389/fphys.2025.1561426","DOIUrl":"10.3389/fphys.2025.1561426","url":null,"abstract":"<p><strong>Introduction: </strong>Optimizing broiler production performance while maintaining digestive health is a key challenge in poultry management. Dietary modifications, including the use of alternative protein sources and enzyme supplementation, can influence growth and gut health.</p><p><strong>Methods: </strong>This study evaluated the effects of roasting, extrusion, and enzymatic supplementation of <i>Vigna unguiculata</i> (cowpeas) and <i>Cajanus cajan</i> (pigeon peas) on growth performance and gut health in broilers. A total of 210 one-day-old Ross male broilers were randomly allocated to seven dietary treatments (five replicates per treatment; six broilers per pen) in a completely randomized design. Experimental diets incorporated raw or heat-treated cowpeas or pigeon peas, with or without a mixed enzyme supplement (protease, xylanase, and phytase), replacing soybean meal at 400 g/kg inclusion.</p><p><strong>Results: </strong>Roasting cowpeas or enzyme supplementation did not significantly affect body weight gain or cumulative performance index (p > 0.05). Roasting pigeon peas significantly improved chick performance (p < 0.05). Broilers fed diets containing raw cowpeas, raw cowpeas with enzymes, and both roasted and raw pigeon peas (with or without enzymes) exhibited reduced duodenal crypt depth compared to the control (p < 0.05). Furthermore, raw cowpeas, irrespective of enzyme supplementation, induced an immune response in the duodenum that was not observed in broilers fed the control diet, roasted cowpeas, or raw pigeon peas.</p><p><strong>Discussion: </strong>Partial substitution of maize and soybean meal with 400 g/kg roasted pigeon peas is a promising alternative in broiler nutrition, enhancing both performance and gut health. However, raw cowpeas may trigger an intestinal immune response, highlighting the importance of processing methods.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1561426"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin resistance, Ca²⁺ signaling alterations and vascular dysfunction in prediabetes and metabolic syndrome.","authors":"Tatiana Romero-García, J Gustavo Vázquez-Jiménez, Rommel Sánchez-Hernández, J Alberto Olivares-Reyes, Angélica Rueda","doi":"10.3389/fphys.2025.1535153","DOIUrl":"10.3389/fphys.2025.1535153","url":null,"abstract":"<p><p>Prediabetes and Metabolic Syndrome (MetS) share a common pathway to induce vascular dysfunction through hyperinsulinemia without the presence of overt hyperglycemia. Insulin resistance (IR) is a key factor in vascular complications in diabetes; however, vascular dysfunction has been reported in MetS patients, even in the absence of chronic hyperglycemic conditions. We consider that the alterations in the intracellular Ca²⁺ handling of vascular smooth muscle cells (VSMCs) and the impairment of the insulin receptor signaling pathway may contribute to the etiology of vascular diseases in prediabetes and MetS. Therefore, it is critical to understand the mechanisms by which prediabetes and MetS alter the expression and activity of proteins involved in intracellular Ca²⁺ signaling in VSMCs, particularly those related to vasorelaxation. The functional unit, integrated by the voltage-gated L-type Ca²⁺ channel (Ca_V1.2), the Sarco/Endoplasmic Reticulum Ca²⁺ ATPase (SERCA pump), the ryanodine receptor (RyR), and the large-conductance Ca²⁺-activated K⁺ channel (BK_Ca), regulates the vascular tone and promotes vasorelaxation of the resistance arteries. Changes in this functional unit may contribute to vascular dysfunction. This review summarizes the most recent knowledge regarding alterations in the expression or activity of these proteins in the vasculature of experimental models with characteristics of prediabetes and MetS.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1535153"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of high-intensity resistance exercise protocols for improving bone mineral density in the elderly without chronic diseases: a systematic review and network meta-analysis.","authors":"Yang Cheng, Yue Yi, Shumin Bo, Jun Mao, Jing Ma","doi":"10.3389/fphys.2025.1589200","DOIUrl":"10.3389/fphys.2025.1589200","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the effects of high-intensity resistance exercise (HIRE) protocols on improving bone mineral density (BMD) in the elderly without chronic diseases by using a forest plot and network meta-analysis.</p><p><strong>Methods: </strong>A systematic search was performed across seven databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Wan Fang and VIP, to investigate the effects of HIRE on BMD in the elderly by December 9, 2024. The search strategy incorporated Boolean operators (AND, OR, NOT) to refine the selection of relevant studies. The methodological quality was assessed by using Risk of Bias tool 2 and Tool for the Assessment of Study Quality and Reporting in Exercise, and data analysis was performed using Stata 17.</p><p><strong>Results: </strong>A total of 13 RCTs involving 616 participants were included. Among the various HIRE protocols, two demonstrated positive effects on lumbar spine and whole-body BMD, while four were positive in improving femoral neck BMD compared to the control group. The network meta-analysis revealed that 3M(9-10) was more effective than 2M(6-8), 3M(6-8) and 1M(6-8) in enhancing lumbar spine BMD. However, no significant differences were observed among the HIRE protocols for femoral neck and whole body BMD. According to the SUCRA rankings, 3M(9-10) was the most effective protocol for improving lumbar spine (94.7%) and femoral neck BMD (82.3%), while 2M(9-10) ranked highest for whole body BMD improvement (61.6%).</p><p><strong>Conclusion: </strong>HIRE protocol is critical to ensure BMD improvement for elderly without chronic diseases, and not all HIRE protocols yield positive effects on BMD. Compared to other sites, lumbar spine BMD appears to be more responsive to HIRE. A 2-3 times, multiple-set regimen may be more beneficial for improving lumbar spine, whole-body, and femoral neck BMD in the elderly, and performing 9-10 repetitions per set is particularly important for improving BMD in older adults.</p><p><strong>Systematic review registration number: </strong>https://www.crd.york.ac.uk/PROSPERO/, identifier registration number. CRD42024543517.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1589200"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternate quantification approaches for cold-induced vasodilation in human glabrous skin.","authors":"J A Stout, D E Gerow, P C Clegg, K Metzler-Wilson, T E Wilson","doi":"10.3389/fphys.2025.1575764","DOIUrl":"10.3389/fphys.2025.1575764","url":null,"abstract":"<p><strong>Introduction: </strong>Cold-induced vasodilation (CIVD) is a counterintuitive focal increase in glabrous skin blood flow during cold exposure with unclear local and neural mechanisms.</p><p><strong>Methods: </strong>We tested 12 (8 men, 4 women) healthy subjects' laser-Doppler flux (LDF; just proximal to the nailbed) and arterial blood pressure (ABP) on a beat-by-beat basis. The experimental hand was exposed to warm (10 min 35°C) and then cold (30 min 8°C) water immersion and the contralateral control hand experienced 22°C-23°C air throughout. We analyzed beat-by-beat oscillations in LDF and ABP via a fast-Fourier transform (FFT) and transfer function analysis (TFA) of LDF to ABP.</p><p><strong>Results: </strong>LDF spectral power was greater in the control finger than immersed fingers in the normalized very low frequency (nVLF) range. There was an interaction in the normalized low frequency (nLF) range where cooling decreased power in immersion sites but increased power in the control site. VLF and LF TFA gains were lower during cooling for immersion but not control sites. Data confirm a significant effect of local vasoconstriction within sympathetic vasoconstriction as identified by changes in VLF and LF, respectively. Comparing CIVD bins (LDF criteria, n = 6) to general cutaneous vasoconstriction bins with no CIVD (n = 6) yielded increased nVLF (P = 0.05) and decreased nLF (P = 0.09) power with CIVD.</p><p><strong>Discussion: </strong>Thus, the unique analysis of LDF and ABP using the FFT-TFA approach appears to be beneficial in providing insights into CIVD events with a periodic local release of vasoconstriction under varying sympathetic tone.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1575764"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between aggregate index of systemic inflammation and DXA-measured body composition parameters in adolescents.","authors":"Haihua Wang, Luping Tao, Zhongxin Zhu","doi":"10.3389/fphys.2025.1612735","DOIUrl":"10.3389/fphys.2025.1612735","url":null,"abstract":"<p><strong>Background: </strong>Systemic inflammation during adolescence may critically influence metabolic and musculoskeletal health, yet comprehensive biomarkers predicting adverse body composition remain underexplored. The aggregate index of systemic inflammation (AISI), integrating neutrophils, platelets, monocytes, and lymphocytes, offers a novel metric to assess this relationship.</p><p><strong>Methods: </strong>This cross-sectional study analyzed 3,661 adolescents (aged 12-19 years) from NHANES 2011-2018. AISI was calculated from complete blood counts, and body composition parameters-appendicular lean mass index (ALMI), visceral adipose tissue area (VATA), and total bone mineral density (BMD)-were measured via dual-energy X-ray absorptiometry (DXA). Multivariable linear regression and threshold effect models evaluated associations, adjusting for demographic, metabolic, and lifestyle covariates.</p><p><strong>Results: </strong>Higher logAISI was associated with lower ALMI (β = -0.189, 95% CI: -0.262 to -0.116), greater VATA (β = 3.017, 1.266-4.769), and reduced BMD (β = -0.017, -0.027 to -0.007). A threshold effect emerged at logAISI = 2.2, beyond which inflammation's impact on VATA and BMD intensified.</p><p><strong>Conclusion: </strong>Elevated AISI correlates with adverse body composition in adolescents. The identified threshold suggests a potential clinical benchmark for early intervention. These findings underscore systemic inflammation as a modifiable target to mitigate metabolic and musculoskeletal risks during this critical developmental period.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1612735"},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of polyethylene terephthalate nanoplastics (PET) on fibroblasts: a study on NIH-3T3 cells.","authors":"Maria Elena Giordano, Francesca Lionetto, Maria Giulia Lionetto","doi":"10.3389/fphys.2025.1580682","DOIUrl":"10.3389/fphys.2025.1580682","url":null,"abstract":"<p><p>Plastic pollution has become a major environmental and public health issue due to rising global production. Nanoplastics (NPs) are especially concerning due to their widespread presence and potential health risks. This study aims to determine the impact of the exposure to polyethylene terephthalate (PET) NPs on fibroblast cells using the murine NIH-3T3 cells as experimental model. This is a relevant cellular model for several biological fields of application, including cell migration in wound healing and tissue regeneration. The PET NPs used represented an environmentally realistic PET NPs model since they were produced by a fast top down approach in a process close to the mechanical abrasion of microplastics occurring in the environment. They were characterized by an intrinsic autofluorescence which enables their use in studies of NPs interactions with biological systems without the need for additional fluorescent dyes. Additionally, the Hansen solubility parameters (HSP) of the PET NPs and the culture medium were determined to better understand their interaction. PET NPs were internalized by fibroblasts in a dose-dependent manner, localizing in the cytoplasm. While they caused only a slight reduction in cell viability (within 20% inhibition at 10-100 μg/mL) after 24 h exposure, they significantly impaired fibroblast migration, as demonstrated by the scratch assay, indicating possible interference in tissue repair. The exposure of the cells to PET NPs induced a significant dose-dependent ROS increase suggesting the induction of intracellular oxidative stress as possible mechanisms underlying the observed migration impairment. These findings highlight the potential risks of PET NPs to fibroblasts, emphasizing the need for further research into their impact on cellular functions and mechanisms.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1580682"},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive biomarker profiling reveals distinct molecular signatures across stone types: a large-scale cross-sectional study in Southern China.","authors":"Qingjiang Chen, Linliang Huang, Suilin Wang, Daqiang Wei, Jiancai Lu, Xiujing Han, Zhenglin Chang","doi":"10.3389/fphys.2025.1612585","DOIUrl":"10.3389/fphys.2025.1612585","url":null,"abstract":"<p><strong>Background: </strong>Stone diseases represent a significant global health burden affecting 10%-15% of the population worldwide. Despite advances in diagnostic imaging, current approaches often lack the ability to predict stone formation or differentiate between stone types at early stages.</p><p><strong>Methods: </strong>This retrospective study analyzed data from 61,310 stone patients and 55,010 matched controls using 1:1 propensity score matching. Stone cases were categorized into five major groups and further subdivided by organ system. Comprehensive serum biomarker profiling was conducted using automated biochemistry analyzers.</p><p><strong>Results: </strong>Urinary system stones constituted the largest proportion (80.97%), followed by biliary system stones (21.12%). The study revealed distinct biomarker signatures: elevated serum creatinine and cystatin C in uric acid stones; increased PSA and monocyte counts in prostatic calculi; elevated β2-microglobulin and total bilirubin in common bile duct stones; and increased basophils, ceruloplasmin, ferritin, immunoglobulin-A, and rheumatoid factor in gallstones.</p><p><strong>Conclusion: </strong>This study represents the first comprehensive evaluation of stone-specific clinical biomarker patterns derived from routine laboratory parameters, providing potential diagnostic markers for different stone types and suggesting stone-specific pathophysiological mechanisms.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1612585"},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromuscular adaptations to resistance training in elite versus recreational athletes.","authors":"Sumaira Aslam, Jean De Dieu Habyarimana, Shi Yong Bin","doi":"10.3389/fphys.2025.1598149","DOIUrl":"10.3389/fphys.2025.1598149","url":null,"abstract":"<p><p>Neuromuscular adaptations to resistance training drive strength and performance improvements, but differences between elite and recreational athletes remain underexplored. Understanding the underlying mechanisms can refine training approaches and enhance athletic development. This review synthesized findings from the past decade regarding how training status, age, sex, and genetics influence neuromuscular adaptations to resistance training, identified key gaps in the literature, and provided practical recommendations for tailoring training to different athletic levels. This critical review synthesized evidence on neuromuscular adaptations to resistance training, focusing on muscle hypertrophy, architectural changes, motor unit recruitment, neural drive, fiber-type transitions, and genetic influences. Methodological limitations and gaps were highlighted, with a focus on elite versus recreational populations. Muscle hypertrophy and strength gains occur rapidly in novices but plateau in advanced athletes, requiring more complex stimuli. Neural adaptations, including improved motor unit synchronization and reduced antagonist co-contraction, distinguish elite from recreational athletes. Genetic predispositions and training history further modulate adaptations. Fatigue, recovery, and injury risk differ between groups, underscoring the need for tailored monitoring and recovery strategies. Research gaps include inconsistent methodologies, limited elite athlete data, and underrepresentation of female cohorts. Future studies should integrate neurophysiological tools and long-term designs to clarify these mechanisms. Effective training requires adjusting intensity and volume based on an athlete's training status. Foundational strength programs benefit youth, while elite athletes require periodization and advanced methods. Policy-level support for supervised resistance training in youth can enhance performance and injury resilience. Addressing these insights can optimize training outcomes across athletic levels.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1598149"},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute kidney injury through a metabolic lens: pathological reprogramming mechanisms and clinical translation potential.","authors":"Jingli Gao, Liuyifei Huang, Yuzhan Zhang, Lei Wei, Zhixiang Yu, Yan Xing, Jinguo Yuan, Xiaoxuan Ning, Shiren Sun","doi":"10.3389/fphys.2025.1602865","DOIUrl":"10.3389/fphys.2025.1602865","url":null,"abstract":"<p><p>Acute kidney injury (AKI) represents a clinical syndrome with a bleak short-term prognosis, posing a high risk for the development of chronic kidney diseases and end-stage kidney disease. The underlying mechanisms of AKI are still not fully understood, and effective intervention strategies remain elusive. Enormous energy is required to meet the functional activity in hypermetabolic tubular epithelial cells (TECs), the most vulnerable cell types during AKI. Recent evidence has shed light on the reprogramming of metabolic pathways and the shift in energy substrates under pathological conditions. The reprogrammed metabolic pathway initially serves to compensate for energy shortages and supply substrates for cell repair during the early stages of AKI. However, sustained metabolic dysregulation tend to become detrimental for tubular repair and regeneration. Intriguingly, dynamic alterations in specific metabolites extend beyond their conventional roles as metabolic byproducts, actively participating in pathophysiology through multifaceted regulatory mechanisms during AKI. As yet, clinical therapy for AKI has not yet incorporated the intervention of metabolic disorders, highlighting a vast potential for extensive application. This review aims to summarize recent studies on the role of metabolic pathway reprogramming and metabolites in AKI, while discussing promising therapeutic strategies targeting metabolic reprogramming.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1602865"},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}