American journal of physiology. Cell physiology最新文献

{"title":"Cdk5rap3-mediated regulation of lysosomal and ER membrane proteins is pivotal for the survival and function of pancreatic acinar cells.","authors":"Yonghong Huang, Feng Zhou, Xin Xu, Yaqun Wang, Michaela Quintero, Siyang Liu, Cong Liu, Guangxun Zhu, Yafei Cai, Zheng Dong, Roni Bollag, Guangyu Wu, Maria Eugenia Sabbatini, Honglin Li","doi":"10.1152/ajpcell.00284.2025","DOIUrl":"10.1152/ajpcell.00284.2025","url":null,"abstract":"<p><p>The acinus is the functional unit of the exocrine pancreas that produces and secretes a large quantity of digestive enzymes. Damage and dysfunction of pancreatic acinar cells (PACs) may lead to malnutrition, pancreatitis, and other pathological conditions. CDK5 regulatory subunit-associated protein 3 (Cdk5rap3), a multifunctional protein, is essential for animal development and normal physiology of multiple organs and tissues. Interestingly, the recent studies suggest its involvement in endoplasmic reticulum (ER)-phagy, a lysosomal degradation of the subdomains of the endoplasmic reticulum (ER). Herein, we attempted to investigate its physiological function in pancreatic acinar cells. We found that <i>Cdk5rap3</i>-deficient PACs contained fewer zymogen granules and underwent acinar-to-ductal metaplasia (ADM) and apoptosis, thereby resulting in a significant loss of acinar compartment. Interestingly, <i>Cdk5rap3</i> ablation led to the increase of lysosomal hydrolase cathepsin B and lysosome-associated membrane protein 1 (LAMP1), indicating its novel function in the regulation of lysosomal homeostasis and activity. Elevated cathepsin B activity may lead to aberrant activation of trypsinogen and apoptosis of <i>Cdk5rap3</i>-deficient acinar cells, whereas the increase of lysosomal proteins may enhance lysosomal activity that in turn promotes ADM. Furthermore, <i>Cdk5rap3</i> knockout led to substantial changes in the rough ER structure and a significant increase in selective ER membrane proteins, including cytoskeleton-linking membrane protein 63 (CLIMP63). Our results from both mouse tissues and tissue culture cells strongly suggest that Cdk5rap3 plays a pivotal role in regulating homeostasis of the lysosome and the ER that is essential for the survival and physiological function of pancreatic acinar cells.<b>NEW & NOTEWORTHY</b> Our current study has demonstrated a critical role of Cdk5rap3 protein in the maintenance and function of pancreatic acinar cells. Cdk5rap3 functions as a key regulator of the homeostasis of subcellular organelles, such as the lysosome and the ER, and its deficiency leads to loss of pancreatic mass and may contribute to the pathogenesis of pancreatic diseases.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C513-C529"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcoplasmic reticulum-mitochondria microdomains: hugging and kissing in the heart.","authors":"Bong Sook Jhun, Jin O-Uchi, Brian Rhee, Ameneh Ahrari, Nathan DeMichaelis, Kye-Im Jeon, David M Booth, Shey-Shing Sheu","doi":"10.1152/ajpcell.00435.2025","DOIUrl":"10.1152/ajpcell.00435.2025","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER)-mitochondrial (ER-Mito) interface, termed mitochondrial-ER contacts (MERCs), plays significant roles in the maintenance of bioenergetics and basal cell functions via the exchange of lipids, Ca²⁺, and reactive oxygen species (ROS) in various cell types/tissues. Genetic deletion of mitofusin 2 (Mfn2), one of the key components of ER-Mito tethering, in cardiomyocytes (CMs) in vivo revealed the importance of the microdomains between mitochondria and sarcoplasmic reticulum (SR), a differentiated form of ER in muscle cells, for maintaining normal mitochondrial Ca²⁺ (mtCa²⁺) handling and bioenergetics in the adult heart. However, key questions remain to be answered: <i>1</i>) What tethering proteins sustain SR-Mito contact site structure in SR-Mito contact sites in the adult ventricular CMs (AVCMs), the predominant cell type in the adult heart? <i>2</i>) Which MERC proteins operate in AVCMs to mediate specific microdomain functions under physiological conditions? and <i>3</i>) How are the MERC protein expression profile and function altered in cardiac pathophysiology? In this review, we summarize current knowledge regarding the structure, function, and regulation of SR-Mito microdomains in the heart, with particular focus on AVCMs, which display unique membrane organization and Ca²⁺ handling compared with other cell types. We further explore molecular mechanisms underpinning microdomain dysfunction in cardiac diseases and highlight the emerging roles of MERC proteins in the development and progression of cardiac pathology.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C599-C610"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentagalloyl glucose inhibits monosodium urate-induced inflammation and NLRP3 inflammasome formation via TAK1.","authors":"Paul M Panipinto, Guihua E Yue, Bhagwat Prasad, Salahuddin Ahmed","doi":"10.1152/ajpcell.00673.2024","DOIUrl":"10.1152/ajpcell.00673.2024","url":null,"abstract":"<p><p>Monosodium urate (MSU)-induced inflammation is caused by the deposition of MSU crystals in the joints and periarticular tissues under conditions of hyperuricemia. These deposits can activate joint resident macrophages that form the NOD-, LRR-, and pyrin-containing protein 3 (NLRP3) inflammasome, cleaving pro-IL-1β and causing inflammation. The present study investigated the anti-inflammatory properties of a polyphenolic compound pentagalloyl glucose (PGG) in MSU-induced inflammation. Pretreatment of THP-1 monocyte-derived macrophages with PGG (0.1-10 µM) caused a dose-dependent inhibition of MSU-induced TAK1^184/187 and NF-κB p65 phosphorylation. PGG significantly reduced the production of pro-IL-1β during the priming phase, which correlated with its inhibition of NLRP3 inflammasome formation as observed by the reduced ASC speck formation and a consequent decrease in IL-8, monocyte chemoattractant protein (MCP-1), and IL-1β production. Using liquid chromatography/mass spectrometry (LC-MS/MS)-based untargeted phosphoproteomics analysis, we discovered 3,919 unique phosphorylation sites modulated by MSU. Of 667 phosphosites upregulated by MSU, PGG selectively suppressed 218, a TAK1 inhibitor (5<i>Z</i>-7-oxozeaenol; 5Z7o) inhibited 134, and both inhibitors commonly inhibited 181. Conversely, 443 total phosphosites were suppressed by MSU that were reduced to only 139 by PGG and 132 by 5Z7o. Administration of PGG (30 mg/kg ip) significantly suppressed MSU-induced paw inflammation in C57BL/6J mice and reduced the time to flare resolution. These findings showed that PGG significantly reduced MSU-induced proinflammatory mediators and inhibited the formation of NLRP3 inflammasomes by primarily targeting the TAK1 pathway. Our finding suggests that dietary supplementation of PGG may help reduce the onset and severity of acute gout flares.<b>NEW & NOTEWORTHY</b> Current treatment options for the management of pain and inflammation in gout are inadequate and expensive. Our study provides a novel mechanism for regulating inflammasome formation and gout flares by a natural polyphenol, pentagalloyl glucose (PGG), that is found in fruits and vegetables. PGG also inhibits xanthine oxidase activity, an enzyme that produces uric acid that contributes to monosodium urate crystal formation, making it a dual inhibitor to be further tested in treating gout.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C500-C512"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose and methylglucose transport in human red blood cells and ghosts.","authors":"Jesper Brahm","doi":"10.1152/ajpcell.00057.2024","DOIUrl":"10.1152/ajpcell.00057.2024","url":null,"abstract":"<p><p>Radioactive labeled d-glucose (GL) or 3-O-methylglucose (MG) efflux from human resealed red ghosts (GHO) or red blood cells (RBC) were determined by means of rapid filtration techniques. All efflux curves show a monoexponential course. Under conditions of self-exchange (SE, equilibrium exchange) and net efflux (NE, zero-trans efflux) in GHO at 0, 10, 25, and 38°C simple Michaelis-Menten-like kinetics in terms of <i>K</i>_½ and <i>J</i>_max apply at 1-200 mM GL. SE conditions: <i>K</i>_½,SE is 19.9, 16.4, 11.2, and 18.0 mM and <i>J</i>_max,SE is 8.7, 42.7, 209, and 555 pmole/(cm² × s); NE conditions: <i>K</i>_½,NE is 9.0, 6.7, 6.5, and 11.5 mM and <i>J</i>_max,NE is 2.8, 18.7, 172, and 680 pmole/(cm² × s). GL SE shows a broad pH dependence with a maximum around pH 7-9. Under SE conditions at 0-38 °C, an overall apparent activation energy, <i>E</i>_A, is 76 kJ/mole. <i>E</i>_A decreases nonlinearly with increasing temperature. A simple two-phase analysis reveals <i>E</i>_A of ≈87 kJ/mole at 0-25°C and ≈49 kJ/mole at 25-38°C. Under NE conditions, <i>E</i>_A shows a linear dependence of 110 kJ/mole at 0-38°C. The data disagree with studies showing a nonlinear <i>E</i>_A of GL and MG transport related to temperature-dependent phase transitions of the lipids in the membrane. Effluxes of GL and MG in normal-sized and swollen RBC with/without 4 mM ATP are all monoexponential, rejecting that ATP generates a biphasic hexose flux pattern. Hetero-exchange with a series of hexoses shows that galactose is best in trans-stimulation, and fructose is best in trans-inhibition of GL efflux. The results disagree with current complicated kinetics models.<b>NEW & NOTEWORTHY</b> Self-exchange (SE) and net efflux (NE) of d-glucose in ghosts are monoexponential. At 0-38°C, glucose SE and NE follow Michaelis-Menten kinetics. Galactose is best in trans-stimulation, fructose is best in trans-inhibition of glucose NE. Temperature dependence of SE and NE is a property of GLUT1, not related to phase transitions of the membrane lipids. Glucose and 3-O-methylglucose SE in RBC with/without 4 mM ATP are monoexponential. ATP stimulates glucose and inhibits 3-O-methylglucose SE.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C395-C411"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of pannexin channels to afterimage signals in the amphibian retina.","authors":"Yufei Liu, Nick Libian, Zheng Jiang, Wen Shen","doi":"10.1152/ajpcell.00028.2025","DOIUrl":"10.1152/ajpcell.00028.2025","url":null,"abstract":"<p><p>Pannexin 1 (Panx1) forms large-pore, single-membrane channels that connect the intracellular and extracellular environments, permitting the passage of ions and small molecules, such as ATP. Panx1 channels are involved in diverse signaling pathways that contribute to various physiological processes, including sensory processing, although their precise mechanisms of action remain incompletely understood. This study reveals a Panx1-mediated mechanism regulating visual signal processing in the amphibian retina. Using immunolabeling and confocal imaging, we localized Panx1 channels in the cone-dominated On-bipolar cells, specifically at both somas and axon terminals. Whole cell patch-clamp recordings showed that these channels have high permeability to Cl^- ions, which can be blocked by ¹⁰Panx1 peptide, carbenoxolone, and mefloquine, all recognized as Panx1 inhibitors. Blocking Panx1 channels or reducing external Cl^- concentrations significantly increased bright light-induced delayed spontaneous excitatory responses in ganglion cells, indicating an inhibitory role of Panx1 channels at the bipolar cell synaptic release. These delayed spontaneous responses in ganglion cells, known as rebound currents, are associated with afterimage signals in the retina. Our findings suggest that Panx1 channels help prevent overexcitation associated with bright light-induced afterimage phenomena.<b>NEW & NOTEWORTHY</b> Cl^- permeable Panx1 channels in the On-bipolar cells serve as a novel mechanism for the negative control of overexcitation in afterimage signal processing in the retina.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C355-C365"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined angiogenic and hypertrophic gene therapy enhances skeletal muscle growth.","authors":"Aino Männistö, Kialiina Tonttila, Alfredo Ortega-Alonso, Harri Nurmi, Liina Uusitalo-Kylmälä, Karthik Amudhala Hemanthakumar, Erik Saikkala, Sami Myllykangas, Satu Vertainen, Tuuli A Nissinen, Arja Pasternack, Olli Ritvos, Kari Kustaa Alitalo, Juha J Hulmi, Riikka Kivelä","doi":"10.1152/ajpcell.00966.2024","DOIUrl":"10.1152/ajpcell.00966.2024","url":null,"abstract":"<p><p>Skeletal muscle atrophy in response to pathophysiological stimuli or disuse includes loss of muscle mass and strength. Targeting signaling pathways regulating muscle growth can counteract muscle loss, but also unwanted side effects on muscle vascularization, oxidative metabolism, and exercise tolerance have been reported. Here, we investigated whether combined induction of angiogenesis and muscle hypertrophy can promote physiological muscle growth and improve muscle function to overcome the limitations of current hypertrophic treatments. We used myostatin propeptide (Pro-MSTN) and vascular endothelial growth factor B (VEGF-B) gene therapies to increase muscle size and angiogenesis, respectively. Intramuscular and systemic adeno-associated viral vector (AAV) delivery was used to study their effects alone and in combination in healthy and diabetic mice. Single-cell RNA sequencing was used to investigate the effects on different cell types and on intercellular communication in the healthy mice. We demonstrate that in the healthy mice, the intramuscular delivery of VEGF-B rescued Pro-MSTN-induced capillary rarefaction and enhanced muscle growth in the combination group (VEGF-B + Pro-MSTN). The systemic combination treatment also improved body composition in the healthy mice and increased muscle mass and grip strength in the diabetic mouse model. The single-cell RNA sequencing data showed that among the nonmyocytes, endothelial cells and pericytes responded the most to both treatments resulting in enhanced intercellular communication. Our findings demonstrate beneficial effects of the combined gene delivery of Pro-MSTN and VEGF-B on muscle growth and body composition. The results also decipher the contribution of various cell types and their cross talk in skeletal muscle growth.<b>NEW & NOTEWORTHY</b> We used intramuscular and systemic adeno-associated viral vector (AAV) gene delivery of myostatin propeptide (Pro-MSTN) and vascular endothelial growth factor B (VEGF-B) to induce muscle growth and angiogenesis in skeletal muscle. The intramuscular delivery of VEGF-B and Pro-MSTN in combination enhanced skeletal muscle growth and rescued vascularization when compared with Pro-MSTN alone. Single-cell RNA sequencing data showed that the treatments had the greatest effect on endothelial cells and pericytes. The combination treatment also improved body composition and muscle mass in diabetic mice, when delivered systemically.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C540-C559"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asprosin attenuates diabetic cardiomyopathy through inhibiting autophagy mediated by AMPK/mTOR/ULK1 pathway.","authors":"Yuan Wang, Wentao Liu, Chen Liu, Zhitong Zhou, Sheng Chen, Qianqian Huang, Li Wang, Guohua Zeng, Qiren Huang","doi":"10.1152/ajpcell.01006.2024","DOIUrl":"10.1152/ajpcell.01006.2024","url":null,"abstract":"<p><p>Aberrant autophagy mediated by AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/unc-51 like kinase 1 (ULK1) pathway (a canonical autophagy pathway) plays important roles in diabetic cardiomyopathy (DCM). Asprosin (ASP) secreted by white adipose tissue involves in systemic metabolism disorders. However, its role in DCM remains poorly understood. Therefore, the purpose of this study was to investigate its roles and underlying mechanisms in the DCM from the perspective of autophagy and apoptosis. In the in vivo experiments, we observed the effects of ASP deficiency (ASP^-/-) or ASP intervention on cardiac function, fibrosis, autophagy, and apoptosis in a diabetes mellitus (DM) mouse model induced by high-fat feeding and streptozotocin (STZ) injection; in the in vitro experiments, we evaluated the effects of ASP intervention with or without 3-methyladenine (3-MA) (autophagy inhibitor) or siAMPK in a H9c2 model injured by high glucose (HG). Our results show that ASP intervention attenuates the myocardial injury induced by DM (<i>P</i> < 0.05) and HG (<i>P</i> < 0.05). In addition, the autophagy level markedly increases (<i>P</i> < 0.05) in diabetic mice, and ASP deficiency worsens the increase induced by DM (<i>P</i> < 0.05). In contrast, ASP intervention alleviates overautophagy induced by DM (<i>P</i> < 0.05) or HG (<i>P</i> < 0.05). Mechanistically, the protective effect of ASP against myocardial injury is through inhibiting the overautophagy mediated by AMPK/mTOR/ULK1 pathway (<i>P</i> < 0.05). Taken together, the findings suggest that ASP would be a potential therapeutic target and the recombinant ASP might be a promising candidate to treat metabolism-associated CVD. Although the findings would present a promise for the treatment of DCM, it is worth noting that the mouse model used fails to fully mimic the human DCM pathophysiology.<b>NEW & NOTEWORTHY</b> We demonstrated for the first time that asprosin (ASP) has protective effects against diabetic cardiomyopathy. We found that ASP could stimulate the AMPK/mTOR/ULK1 pathway to reduce the level of autophagy and apoptosis of cardiomyocytes, thereby maintaining the normal physiological function of the heart.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C377-C394"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction for Wang and Gao.","authors":"","doi":"10.1152/ajpcell.00481.2024","DOIUrl":"10.1152/ajpcell.00481.2024","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C480"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postexercise ketone monoester administration concomitant with glucose stimulates glycogen repletion in soleus muscle in mice.","authors":"Yumiko Takahashi, Tatsuya Matsumoto, Wenxin Wang, Takeru Inaba, Shin Terada, Hideo Hatta","doi":"10.1152/ajpcell.00311.2025","DOIUrl":"10.1152/ajpcell.00311.2025","url":null,"abstract":"<p><p>Although our group has demonstrated that the administration of β-hydroxybutyrate, a major type of ketone body, stimulated postexercise glycogen repletion in isolated skeletal muscle, investigations of the effects of ketone supplementation on postexercise muscle glycogen repletion in vivo have obtained conflicting results. Here, we investigated the effects of an oral intake of the ketone monoester [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate] on postexercise glycogen repletion in mouse skeletal muscles. Ten-week-old male Institute of Cancer Research mice ran on a treadmill at 25 m/min speed for 60 min. Immediately after the exercise, the mice were orally administered a solution containing 1.0 g/kg body wt (BW) of glucose and 2.0 g/kg BW of ketone monoester (KE solution) or a solution containing glucose and 1.11 g/kg BW of triolein for the adjustment of total calories to match the KE solution's (Con solution). The KE-treated group showed significantly lower postadministration blood glucose concentrations and higher plasma insulin concentrations compared with those of the Con-treated group. The KE-treated group showed a 42.1% higher glycogen concentration in soleus muscle (slow-twitch fiber-dominant) at 60 min postadministration compared with that of the Con group. There was no significant between-group difference in the glycogen concentration in the plantaris muscle (fast-twitch fiber-dominant). The KE-treated group's soleus muscle also showed significantly lower phosphorylation levels of AMP-activated kinase Thr¹⁷² at 30 min postexercise compared with the level immediately postexercise. These results demonstrated that a postexercise administration of ketone monoester enhanced glycogen repletion, particularly in slow-twitch fiber-dominant muscle.<b>NEW & NOTEWORTHY</b> This is the first study to compare the effects of postexercise ketone body intake on glycogen repletion in fast-twitch fiber- and slow-twitch fiber-dominant muscles. A postexercise administration of ketone monoester together with glucose enhanced the glycogen repletion in murine slow-twitch fiber-dominant muscle but not in fast-twitch fiber-dominant muscle. The ketone monoester intake also elicited higher insulin levels in plasma and lower AMPK phosphorylation levels in soleus muscle during the postexercise phase.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C366-C376"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dysregulation of trained immunity in immune aging and the impact of dietary patterns.","authors":"Andra Grigorescu, Anca-Lelia Riza, Ioana Streata, Mihai G Netea","doi":"10.1152/ajpcell.00153.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00153.2025","url":null,"abstract":"<p><p>Trained immunity (TRIM) is the process through which the innate immune system undergoes memory-like epigenetic and metabolic reprogramming following an earlier infectious challenge. Trained immunity can be induced, in a similar fashion to microbial structures, by various endogenous compounds: oxidized low-density lipoproteins, lipoprotein(a), glucose and uric acid, and monosodium urate. Lipids, glucose, and protein metabolic dysfunction have the potential to perpetuate a proinflammatory feedback loop through the induction of maladaptive trained immunity programs, as shown in cardiovascular diseases, diabetes, and hyperuricemia. Molecular mechanisms leading to TRIM are susceptible to homeostatic disruptions of advanced age, and maladaptive TRIM may be the link between immune aging and age-associated pathologies. The present review discusses the current knowledge on metabolic pathways in adaptive and maladaptive trained immunity and its deleterious consequences of inappropriate activation during aging. Finally, we discuss how several dietary patterns modulate immunometabolism and influence trained immunity in aging.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"329 2","pages":"C456-C470"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}