Acta Physiologica最新文献

{"title":"Augmenter of liver regeneration knockout aggravates tubular ferroptosis and macrophage activation by regulating carnitine palmitoyltransferase-1A-induced lipid metabolism in diabetic nephropathy","authors":"Yuanyuan Zhang,&nbsp;Zheng Zhang,&nbsp;Lili Huang,&nbsp;Chunxia Wang,&nbsp;Pengfei Yang,&nbsp;Ling Zhang,&nbsp;Xiaohui Liao","doi":"10.1111/apha.14159","DOIUrl":"10.1111/apha.14159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Ferroptosis is a novel type of programmed cell death that performs a critical function in diabetic nephropathy (DN). Augmenter of liver regeneration (ALR) exists in the inner membrane of mitochondria, and inhibits inflammation, apoptosis, and oxidative stress in acute kidney injury; however, its role in DN remains unexplored. Here, we aimed to identify the role of ALR in ferroptosis induction and macrophage activation in DN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of ALR was examined in DN patients, db/db DN mice, and HK-2 cells treated with high glucose (HG). The effects of ALR on ferroptosis and macrophage activation were investigated with ALR conditional knockout, lentivirus transfection, transmission electron microscopy, qRT-PCR and western blotting assay. Mass spectrometry and rescue experiments were conducted to determine the mechanism of ALR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ALR expression was reduced in the kidney tissues of DN patients and mice, serum of DN patients, and HG-HK-2 cells. Moreover, the inhibition of ALR promoted ferroptosis, macrophage activation, and DN progression. Mechanistically, ALR can directly bind to carnitine palmitoyltransferase-1A (CPT1A), the key rate-limiting enzyme of fatty acid oxidation (FAO), and inhibit the expression of CPT1A to regulate lipid metabolism involving FAO and lipid droplet-mitochondrial coupling in DN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, our findings revealed a crucial protective role of ALR in ferroptosis induction and macrophage activation in DN and identified it as an alternative diagnostic marker and therapeutic target for DN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066686","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":"Lasting consequences of cigarette smoking on the heart","authors":"Ghadir Amin,&nbsp;George W. Booz,&nbsp;Fouad A. Zouein","doi":"10.1111/apha.14166","DOIUrl":"10.1111/apha.14166","url":null,"abstract":"&lt;p&gt;Smoking is associated with increased morbidity and mortality and can harm almost every organ in the body. The risk reduction for cardiovascular diseases with smoking cessation is well documented by numerous clinical studies,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; but long-term adverse consequences persist. For instance, the risk for cardiovascular complications remains high for ex-smokers, and former heavy smokers have a higher incidence of left ventricular systolic dysfunction, coronary artery and peripheral arterial diseases, and type 2 diabetes. Surprisingly, little is known about the adverse effects that persist in the heart following smoking cessation.&lt;/p&gt;&lt;p&gt;In this issue, Dr. Wüst and colleagues investigated what happens in the heart following smoking cessation on the metabolic, lipidomic, and structural remodeling seen with smoking (Table 1).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; It is well established that smoking stimulates cardiovascular remodeling by interdependent pathways involving inflammation, oxidative stress, mitochondrial dysfunction, and hyperlipidemia.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Using mice, the study conducted by Wüst and colleagues revealed both the reversible and durable effects of smoking on the heart after a cessation period of up to 2 weeks.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Provoked local inflammation and cardiac fibrosis were among the consequences that are not mitigated by short-term cessation. Their findings suggest that a persistent infiltration of macrophages induced by smoking may foster a profibrotic milieu, which increases the risk of a proatherogenic response and cardiovascular complications, such as diastolic dysfunction and arrhythmias.&lt;/p&gt;&lt;p&gt;Quitting smoking may often lead to weight gain, which is a primary concern for contributing to insulin resistance and increasing the inflammatory response and metabolic burden. The study discussed found that smoking exposure causes weight loss and increases long and very long-chain fatty acids in the heart. Upon cessation, mice experienced weight gain and a further increase in their lipid profile. Direct and indirect mechanisms mediated by nicotine or smoking-induced insulin resistance can lead to smoking-induced high lipid profiles. However, weight gain might become an important regulator of metabolism following cessation. Some clinical studies suggest that these effects are typically temporary and tend to reverse after 6 months in humans.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Conversely, there have been reports that suggest a correlation between weight gain and attenuation in the benefit of cessation on the risk of cardiovascular disease.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In addition to the well-known connection between obesity and lipid buildup, Wüst and colleagues discovered evidence of a possible shift in metabolism from fatty acids to glucose after 2 weeks of cessation.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This shift was indicated by higher levels of long-chain fatty acids and increased glycolytic intermediates, suggesting a po","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955236","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":"Resistance exercise upregulates Irisin expression and suppresses myocardial fibrosis following myocardial infarction via activating AMPK-Sirt1 and inactivating TGFβ1-Smad2/3","authors":"Hangzhuo Li,&nbsp;Shuguang Qin,&nbsp;Jie Tang,&nbsp;Tao Wang,&nbsp;Wujing Ren,&nbsp;Lingyun Di,&nbsp;Wenyan Bo,&nbsp;Yixuan Ma,&nbsp;Fangnan Wu,&nbsp;Zujie Xu,&nbsp;Wei Song,&nbsp;Mengxin Cai,&nbsp;Yue Xi,&nbsp;Zhenjun Tian","doi":"10.1111/apha.14163","DOIUrl":"10.1111/apha.14163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The MI model was built by ligating the left anterior descending coronary artery in <i>Fndc5</i> knockout mice (<i>Fndc5</i>^−/−). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H₂O₂, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-<i>Sirt1</i> shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Resistance exercise increased <i>Fndc5</i> mRNA level, inhibited the activation of TGFβ1-TGFβR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, <i>Fndc5</i> knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the <i>in vitro</i> experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFβ1-Smad2/3 pathway, and promoted apoptosis in H₂O₂-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFβR2 expression, were attenuated by LV-<i>Sirt1</i> shRNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Resistance exercise upregulates <i>Fndc5</i> expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFβ1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How calcineurin inhibitors affect cognition","authors":"Kitti Thiankhaw,&nbsp;Nipon Chattipakorn,&nbsp;Siripron C. Chattipakorn","doi":"10.1111/apha.14161","DOIUrl":"10.1111/apha.14161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>With a focus on the discrepancy between preclinical and clinical findings, this review will gather comprehensive information about the effects of calcineurin inhibitors (CNI) on cognitive function and related brain pathology from <i>in vitro</i>, <i>in vivo</i>, and clinical studies. We also summarize the potential mechanisms that underlie the pathways related to CNI-induced cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched articles in PubMed using keywords ‘calcineurin inhibitor*’ and ‘cognition’ to identify related articles, which the final list pertaining to underlying mechanisms of CNI on cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Several studies have reported an association between calcineurin and the neuropathology of Alzheimer’s disease (AD). AD is the most common neurocognitive disorder associated with amyloid plaques and neurofibrillary tangles in the brain, leading to cognitive impairment. CNI, including tacrolimus and cyclosporin A, are commonly prescribed for patients with transplantation of solid organs such as kidney, liver, or heart, those drugs are currently being used as long-term immunosuppressive therapy. Although preclinical models emphasize the favorable effects of CNI on the restoration of brain pathology due to the impacts of calcineurin on the alleviation of amyloid-beta deposition and tau hyperphosphorylation, or rescuing synaptic and mitochondrial functions, treatment-related neurotoxicity, resulting in cognitive dysfunctions has been observed in clinical settings of patients who received CNI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Inconsistent results of CNI on cognition from clinical studies have been observed due to impairment of the blood-brain barrier, neuroinflammation mediated by reactive oxygen species, and alteration in mitochondrial fission, and extended research is required to confirm its promising use in cognitive impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered skeletal muscle function and beneficial effects of exercise training in a rat model of induced pulmonary emphysema","authors":"Emilie Passerieux,&nbsp;Elodie Desplanche,&nbsp;Laurie Alburquerque,&nbsp;Quentin Wynands,&nbsp;Axel Bellanger,&nbsp;Anne Virsolvy,&nbsp;Farés Gouzi,&nbsp;Olivier Cazorla,&nbsp;Arnaud Bourdin,&nbsp;Maurice Hayot,&nbsp;Pascal Pomiès","doi":"10.1111/apha.14165","DOIUrl":"10.1111/apha.14165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and development of emphysema. Among the comorbidities associated with COPD, skeletal muscle dysfunction is known to affect exercise capacity and the survival rate of patients. Pulmonary rehabilitation (PR), via exercise training, is essential for COPD patients. However, the response to PR is most often moderate. An animal model that recapitulates critical features of chronic human disease and provides access to muscle function should therefore be useful to improve PR benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used a rat model of induced emphysema based on pulmonary instillations of elastase (ELA) and lipopolysaccharides (LPS). We assessed the long-term effects of ELA/LPS and the potential effectiveness of endurance training on the skeletal muscle function. In vivo strength of the animals, and ex vivo contractility, endurance, type 1 fiber proportion, fiber cross-sectional area, and capillarization of both soleus and extensor digitorum longus (EDL) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An impaired overall muscle strength with decreased force, reduced capillarization, and atrophy of type 1 fiber of EDL was observed in ELA/LPS rats. Soleus was not affected. Endurance training was able to reduce fatigability, and increase type 1 fiber proportion and capillarization of soleus, and improve force, endurance, and capillarization of EDL in control and ELA/LPS rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our rat model of induced emphysema, which shares some features with the phenotype present in patients with COPD, could represent a suitable model to study skeletal muscle dysfunction and the effects of exercise training on muscle function in patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920143","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":"Striatin knock out induces a gain of function of INa and impaired Ca2+ handling in mESC-derived cardiomyocytes","authors":"P. Benzoni,&nbsp;M. Arici,&nbsp;F. Giannetti,&nbsp;A. Cospito,&nbsp;R. Prevostini,&nbsp;C. Volani,&nbsp;L. Fassina,&nbsp;M. D. Rosato-Siri,&nbsp;A. Metallo,&nbsp;L. Gennaccaro,&nbsp;S. Suffredini,&nbsp;L. Foco,&nbsp;S. Mazzetti,&nbsp;A. Calogero,&nbsp;G. Cappelletti,&nbsp;A. Leibbrandt,&nbsp;U. Elling,&nbsp;F. Broso,&nbsp;J. M. Penninger,&nbsp;P. P. Pramstaller,&nbsp;C. Piubelli,&nbsp;A. Bucchi,&nbsp;M. Baruscotti,&nbsp;A. Rossini,&nbsp;M. Rocchetti,&nbsp;A. Barbuti","doi":"10.1111/apha.14160","DOIUrl":"10.1111/apha.14160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied the role(s) of cardiac Strn gene (<i>STRN</i>) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast I_Na conductance and no changes in I_f. Paced (2–8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in I_CaL and I_Kr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca²⁺, caused by an enhanced late Na⁺ current density (I_NaL) and a reduced Na⁺/Ca²⁺ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na⁺ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of I_Na conductance toward WT levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Loss of <i>STRN</i> alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na⁺ channels trafficking to the plasma membrane, causing a global Na⁺ and Ca²⁺ enhancement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920145","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":"Mitochondrial function in skeletal muscle contributes to reproductive endothermy in tegu lizards (Salvator merianae)","authors":"Livia Saccani Hervas,&nbsp;Lara do Amaral-Silva,&nbsp;Marina Rincon Sartori,&nbsp;Ane Guadalupe-Silva,&nbsp;Luciane H. Gargaglioni,&nbsp;Johannes Lerchner,&nbsp;Marcos Túlio Oliveira,&nbsp;Kênia Cardoso Bícego","doi":"10.1111/apha.14162","DOIUrl":"10.1111/apha.14162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In cyclic climate variations, including seasonal changes, many animals regulate their energy demands to overcome critical transitory moments, restricting their high-demand activities to phases of resource abundance, enabling rapid growth and reproduction. Tegu lizards (<i>Salvator merianae</i>) are ectotherms with a robust annual cycle, being active during summer, hibernating during winter, and presenting a remarkable endothermy during reproduction in spring. Here, we evaluated whether changes in mitochondrial respiratory physiology in skeletal muscle could serve as a mechanism for the increased thermogenesis observed during the tegu's reproductive endothermy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed high-resolution respirometry and calorimetry in permeabilized red and white muscle fibers, sampled during summer (activity) and spring (high activity and reproduction), in association with citrate synthase measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During spring, the muscle fibers exhibited increased oxidative phosphorylation. They also enhanced uncoupled respiration and heat production via adenine nucleotide translocase (ANT), but not via uncoupling proteins (UCP). Citrate synthase activity was higher during the spring, suggesting greater mitochondrial density compared to the summer. These findings were consistent across both sexes and muscle types (red and white).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The current results highlight potential cellular thermogenic mechanisms in an ectothermic reptile that contribute to transient endothermy. Our study indicates that the unique feature of transitioning to endothermy through nonshivering thermogenesis during the reproductive phase may be facilitated by higher mitochondrial density, function, and uncoupling within the skeletal muscle. This knowledge contributes significant elements to the broader picture of models for the evolution of endothermy, particularly in relation to the enhancement of aerobic capacity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-dependent reduction in oxidative capacity among cultured myotubes from spinal cord injured individuals","authors":"Stanislava Stevanovic,&nbsp;Andrea Dalmao-Fernandez,&nbsp;Derya Mohamed,&nbsp;Tuula A. Nyman,&nbsp;Emil Kostovski,&nbsp;Per Ole Iversen,&nbsp;Mladen Savikj,&nbsp;Natasa Nikolic,&nbsp;Arild C. Rustan,&nbsp;G. Hege Thoresen,&nbsp;Eili T. Kase","doi":"10.1111/apha.14156","DOIUrl":"10.1111/apha.14156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To characterize inactivity-related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from <i>musculus vastus lateralis</i> from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of <i>PPARGC1α</i>, the master regulator of mitochondrial biogenesis, and <i>MYH2</i>, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848906","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":"Regulation of placental amino acid transport in health and disease","authors":"Hiroshi Shimada,&nbsp;Theresa L. Powell,&nbsp;Thomas Jansson","doi":"10.1111/apha.14157","DOIUrl":"10.1111/apha.14157","url":null,"abstract":"<p>Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF-1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast-specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short- and long-term consequences of abnormal fetal growth in the future.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of thiazides and new findings on kidney stones and dysglycemic side effects","authors":"Matteo Bargagli,&nbsp;Manuel A. Anderegg,&nbsp;Daniel G. Fuster","doi":"10.1111/apha.14155","DOIUrl":"10.1111/apha.14155","url":null,"abstract":"<p>Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834350","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}