Acta Physiologica最新文献

{"title":"Calcineurin inhibitors and the renin–angiotensin–aldosterone system","authors":"Mesut Berber,&nbsp;David Penton","doi":"10.1111/apha.14248","DOIUrl":"10.1111/apha.14248","url":null,"abstract":"<p>Calcineurin inhibitors (CnIs) are effective immunosuppressants with decades of accumulated experience in treating immune disorders and, most notably, solid organ transplantation. While CnIs have significantly increased graft survival and transformed the patient standard of care, their use has been overshadowed by a number of undesired side effects. For instance, CnI-associated nephrotoxicity has been reported since early studies and remains a major therapeutic concern. The occurrence of several ion imbalances alongside hypertension was also noted early on, indicating the involvement of the renin–angiotensin–aldosterone system (RAAS) in CnI-mediated toxicity. However, the literature in this field is crowded with conflicting reports from clinical trials as well as studies using animal and invitro models. With this review, we aim to provide a structured and updated overview of the physiological and pathophysiological evidence supporting the involvement of the classical RAAS in CnI-associated toxicity.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491348","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":"High chloride induces aldosterone resistance in the distal nephron.","authors":"Helga Vitzthum, Nina Hauswald, Helena Pham, Leya Eckermann-Reimer, Catherine Meyer-Schwesinger, Heimo Ehmke","doi":"10.1111/apha.14246","DOIUrl":"https://doi.org/10.1111/apha.14246","url":null,"abstract":"<p><strong>Aim: </strong>Increasing the dietary intake of K⁺ in the setting of a high salt intake promotes renal Na⁺ excretion even though K⁺ concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na⁺ reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na⁺ reabsorption after high K⁺ intake.</p><p><strong>Methods: </strong>Mice were fed diets containing varying amounts of Na⁺ combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl^-]. The response to aldosterone was analyzed by high-resolution imaging and by biochemical approaches.</p><p><strong>Results: </strong>The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na⁺ channel ENaC was repressed in Na⁺-replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na⁺-replete mice when the extracellular [Cl^-] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl^-] was sufficient to disrupt the aldosterone-induced MR translocation.</p><p><strong>Conclusion: </strong>These findings indicate a pivotal role for extracellular [Cl^-] in modulating renal aldosterone signaling to adapt MR activation by a high K⁺ intake to the NaCl balance. An impairment of [Cl^-]-mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":" ","pages":"e14246"},"PeriodicalIF":5.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491350","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":"The effects of cannabinoids on the kidney","authors":"Steven Didik,&nbsp;Oleg Palygin,&nbsp;Mark Chandy,&nbsp;Alexander Staruschenko","doi":"10.1111/apha.14247","DOIUrl":"10.1111/apha.14247","url":null,"abstract":"<p>Cannabinoids are a class of drugs derived from the <i>Cannabis</i> plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2-arachidonoylglycerol (2-AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied. However, their effects on peripheral organs, such as the kidneys, require further examination. With dramatic rises in use, production, and legalization, it is essential to understand the impact and mechanistic properties of these drugs as they pertain to renal and cardiovascular physiology. The goal of this review is to summarize prior literature on the expression of cannabinoid receptors and how cannabinoids influence renal function. This review first discusses the interaction of the endocannabinoid system (ECS) and renal physiology and pathophysiology. Following, we briefly discuss the role of the ECS in various kidney diseases and the potential therapeutic applications of drugs targeting the cannabinoid system. Lastly, recent studies have identified several detrimental effects of cannabinoids, not only on the kidney but also in contributing to adverse cardiovascular outcomes. Thus, the negative impact of cannabinoids on renal function and the development of various cardiovascular diseases is also discussed.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491351","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":"Histone deacetylase 6 inhibition promotes microtubule acetylation and facilitates autophagosome-lysosome fusion in dystrophin-deficient mdx mice.","authors":"Akanksha Agrawal, Erin L Clayton, Courtney L Cavazos, Benjamin A Clayton, George G Rodney","doi":"10.1111/apha.14243","DOIUrl":"https://doi.org/10.1111/apha.14243","url":null,"abstract":"<p><strong>Aim: </strong>Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.</p><p><strong>Methods: </strong>Mdx mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and pathophysiology was assessed. Mdx mice with a genetic deletion of the Nox-2 scaffolding subunit p47^phox were used to assess redox dependence on tubulin acetylation.</p><p><strong>Results: </strong>Our data show decreased acetylation of α-tubulin with enhanced histone deacetylase 6 expression. Tubastatin A increases tubulin acetylation and Q-SNARE complex formation but does not alter microtubule organization or density, indicating improved autophagosome-lysosome fusion. Tubastatin A increases the acetylation of peroxiredoxin and protects it from hyper-oxidation, hence modulating intracellular redox status in mdx mice. Tubastatin A reduces muscle damage and enhances force production. Genetic down regulation of Nox2 activity in the mdx mice promotes autophagosome maturation but not autolysosome formation.</p><p><strong>Conclusion: </strong>Our data highlight that autophagy is differentially regulated by redox and acetylation in mdx mice. By improving autophagy through promoting tubulin acetylation, Tubastatin A decreases the dystrophic phenotype and improves muscle function, suggesting a great potential for clinical translation and treating dystrophic patients.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":" ","pages":"e14243"},"PeriodicalIF":5.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453748","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":"Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury.","authors":"Vera A Kulow, Kameliya Roegner, Robert Labes, Mumtaz Kasim, Susanne Mathia, Claudia S Czopek, Nikolaus Berndt, Philipp N Becker, Gohar Ter-Avetisyan, Friedrich C Luft, Philipp Enghard, Christian Hinze, Jan Klocke, Kai-Uwe Eckardt, Kai M Schmidt-Ott, Pontus B Persson, Christian Rosenberger, Michael Fähling","doi":"10.1111/apha.14242","DOIUrl":"https://doi.org/10.1111/apha.14242","url":null,"abstract":"<p><strong>Aim: </strong>2,3-bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney.</p><p><strong>Methods: </strong>A tubular-specific, doxycycline-inducible Bpgm-knockout mouse model was generated. Histological, immunofluorescence, and proteomic analyses were conducted to examine the localization of BPGM expression and the impact of its knockout on kidney structure and function. In vitro studies were performed to investigate the metabolic consequences of Bpgm knockdown under osmotic stress.</p><p><strong>Results: </strong>BPGM expression was localized to the distal nephron and was absent in proximal tubules. Inducible knockout of Bpgm resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed involvement of BPGM in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation. In vitro, Bpgm knockdown led to enhanced glycolysis, decreased reactive oxygen species elimination capacity under osmotic stress, and increased apoptosis. Furthermore, interactions between nephron segments and immune cells in the kidney suggested a mechanism for propagating stress signals from distal to proximal tubules.</p><p><strong>Conclusion: </strong>BPGM fulfills critical functions beyond the erythrocyte in maintaining glucose metabolism in the distal nephron. Its absence leads to metabolic imbalances, increased oxidative stress, inflammation, and ultimately kidney injury.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":" ","pages":"e14242"},"PeriodicalIF":5.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453747","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":"SUMO: A new perspective to decipher fibrosis","authors":"Ling Li,&nbsp;Ping-Ping Gao,&nbsp;Ting-Ting Chen,&nbsp;Nan Li,&nbsp;Hui-Juan Zhang,&nbsp;Meng-Qi Li,&nbsp;Ya-Ning Chen,&nbsp;Wei Wei,&nbsp;Hua Wang,&nbsp;Wu-Yi Sun","doi":"10.1111/apha.14240","DOIUrl":"10.1111/apha.14240","url":null,"abstract":"<p>Fibrosis is characterized by excessive extracellular matrix (ECM) deposition resulting from dysregulated wound healing and connective tissue repair mechanisms. Excessive accumulation of ECM leads to fibrous tissue formation, impairing organ function and driving the progression of various fibrotic diseases. Recently, the role of small ubiquitin-like modifiers (SUMO) in fibrotic diseases has attracted significant attention. SUMO-mediated SUMOylation, a highly conserved posttranslational modification, participates in a variety of biological processes, including nuclear-cytosolic transport, cell cycle progression, DNA damage repair, and cellular metabolism. Conversely, SUMO-specific proteases cleave the isopeptide bond of SUMO conjugates, thereby regulating the deSUMOylation process. Mounting evidence indicates that SUMOylation and deSUMOylation regulate the functions of several proteins, such as Smad3, NF-κB, and promyelocytic leukemia protein, which are implicated in fibrotic diseases like liver fibrosis, myocardial fibrosis, and pulmonary fibrosis. This review summarizes the role of SUMO in fibrosis-related pathways and explores its pathological relevance in various fibrotic diseases. All evidence suggest that the SUMO pathway is important targets for the development of treatments for fibrotic diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453749","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":"Adipose endothelin signaling—An unusual suspect linking obesity to insulin resistance","authors":"Henrik Oster","doi":"10.1111/apha.14241","DOIUrl":"10.1111/apha.14241","url":null,"abstract":"&lt;p&gt;Endothelins are peptide hormones best known for their function in the regulation of vessel tone. They are mainly secreted by endothelial cells, but expression has been reported for many other tissues including liver, muscle, adipose tissues, and the brain.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The main of the three endothelin isoforms, endothelin-1 (ET-1), is the most potent natural vasoconstrictor known so far and has been implicated in a broad range of cardiovascular diseases. Interestingly, increased ET-1 levels are also reported in obese and diabetic patients, and ET-1 signaling through one of its two receptors, endothelin receptor beta (ET&lt;sub&gt;B&lt;/sub&gt;), has been implicated in the regulation of insulin action and glucose homeostasis.&lt;/p&gt;&lt;p&gt;In this issue, Rivera-Gonzalez and co-workers studied the metabolic function of ET-1/ET&lt;sub&gt;B&lt;/sub&gt; signaling in a mouse model of diet-induced obesity.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Their data suggest that ET-1-induced ET&lt;sub&gt;B&lt;/sub&gt; signaling in adipose tissues inhibits the expression and release of the adipokine hormone adiponectin. This, in turn, is a well-known sensitizer of insulin signaling and glucose import and metabolization in tissues, such as adipose, muscle, and liver.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The new data offer an intriguing mechanistic explanation for the metabolic function of ET-1 signaling: obesity-induced upregulation of ET-1 expression leads to ET&lt;sub&gt;B&lt;/sub&gt;-mediated downregulation of adiponectin release from adipocytes. Diminished adiponectin levels in the circulation, in turn, would desensitize insulin signaling and glucose disposal in target tissues promoting hyperglycemia and the development of insulin resistance (Figure 1).&lt;/p&gt;&lt;p&gt;The authors of this study provide several lines of evidence supporting their conclusions. First, they studied metabolic responses to ET-1 treatment in primary adipocytes upon genetic or pharmacological inhibition of ET&lt;sub&gt;B&lt;/sub&gt; signaling. They show that ET-1 downregulates expression of the master metabolic transcriptional regulator, peroxisome proliferator-activated receptor gamma (&lt;i&gt;Pparγ&lt;/i&gt;), and adiponectin (&lt;i&gt;Adipoq&lt;/i&gt;). Second, they generated mice that specifically carry a knockout of or overexpress ET&lt;sub&gt;B&lt;/sub&gt; in adipose tissue. By adipose tissue RNA-sequencing, they show that genes associated with metabolic pathways like insulin and adipokine signaling are upregulated in ET&lt;sub&gt;B&lt;/sub&gt; knockout animals under high-fat-diet conditions. These include insulin receptor 1 (&lt;i&gt;Irs-1&lt;/i&gt;), the insulin-dependent glucose transporter GLUT4 (&lt;i&gt;Slc2a4&lt;/i&gt;), and adiponectin (&lt;i&gt;Adipoq&lt;/i&gt;). Effects on other adipokines such as leptin and adipsin were also observed suggesting a pro-obesogenic action of ET-1 in adipose tissue. These effects were more pronounced in—hormonally more active—visceral compared to subcutaneous adipose depots. Finally, knockout of ET&lt;sub&gt;B&lt;/sub&gt; improved insulin sensitivity and glucose handling in obese animals, while ET&lt;sub&gt;B&lt;/sub&gt; overexpressio","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386490","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":"Mats Wolgast (1935–2024)—Obituary","authors":"Bertil Karlmark,&nbsp;Örjan Källskog,&nbsp;Peter Hansell,&nbsp;Mikael Broman,&nbsp;Mats Sjöquist","doi":"10.1111/apha.14235","DOIUrl":"10.1111/apha.14235","url":null,"abstract":"&lt;p&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;It is with great sadness that we announce to the renal community the passing of Professor emeritus in Physiology Mats Wolgast, Uppsala, Sweden. The closest mourners are the children Charlotta from his marriage to the late Inger Söder Wolgast, and Björn and Åsa from his previous marriage. He died after a period of illness at the age of 89.&lt;/p&gt;&lt;p&gt;Mats grew up in Bräkne-Hoby, a small town in the county of Blekinge, graduated in Helsingborg and studied medicine in Uppsala. He was instantly hooked on the subject of physiology and remained at the Department of Physiology in Uppsala after his medical studies where he graduated as a PhD in 1968.&lt;/p&gt;&lt;p&gt;Mats was a genius with the ability to see context and consequences long before the rest of us. The kidney became his main interest and the thesis in 1968 concerned the distribution of blood within the kidney with focus on the medulla with the essence being published in Nature&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and Acta Physiologica Scandinavica.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; A special room was built at the Biomedical Center for his research with radioactive red blood cells and tailored semiconductor detectors. When the work received a lot of international attention, he became a leading figure in the successful Kidney Research Group whose PhD students were welcomed at many research centers worldwide. He also studied permeability characteristics of charged biological membranes and the interstitial space using complicated mathematical models to explain the gel concept&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; which probably interfered with the ability to sleep of several referees and journal editors. Some even say he invented his own mathematics. He was also well known for his studies in revealing the dynamics of glomerular filtration.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Doctors in internal medicine, surgery, radiology, and nephrology approached Mats not only for help but also for collaboration. The need and existence of a sharp theoretical and practical physiologist became the foundation for a large number of clinical dissertations in a variety of fields such as ischemia–reperfusion injury, transplantation, acute kidney injury, and oxidative stress. His last publication at the age of 82 concerned renal autoregulation during hypothermia.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Gray-haired doctors of today especially remember Mats Wolgast from the Physiology course, perhaps because he always had highly appreciated lectures—educational, instructive, and, to say the least, colorful. Many of his jokes and pranks during lectures are still remembered with great joy, but some of them would probably not survive todays strict woke dogma in the educational system.&lt;/p&gt;&lt;p&gt;He was also an environmental pioneer, built two environmental houses, and became an acclaimed national celebrity. Soon, busloads of journalists and other stakeholders made the pilgrimage to the family's home in the suburb Sunnersta mainly during weekends and Mats ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379557","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":"Getting in the zone: Metabolite transport across liver zones","authors":"Stan F. J. van de Graaf,&nbsp;Coen C. Paulusma,&nbsp;Wietse In het Panhuis","doi":"10.1111/apha.14239","DOIUrl":"10.1111/apha.14239","url":null,"abstract":"<p>The liver has many functions including the regulation of nutrient and metabolite levels in the systemic circulation through efficient transport into and out of hepatocytes. To sustain these functions, hepatocytes display large functional heterogeneity. This heterogeneity is reflected by zonation of metabolic processes that take place in different zones of the liver lobule, where nutrient-rich blood enters the liver in the periportal zone and flows through the mid-zone prior to drainage by a central vein in the pericentral zone. Metabolite transport plays a pivotal role in the division of labor across liver zones, being either transport into the hepatocyte or transport between hepatocytes through the blood. Signaling pathways that regulate zonation, such as Wnt/β-catenin, have been shown to play a causal role in the development of metabolic dysfunction-associated steatohepatitis (MASH) progression, but the (patho)physiological regulation of metabolite transport remains enigmatic. Despite the practical challenges to separately study individual liver zones, technological advancements in the recent years have greatly improved insight in spatially divided metabolite transport. This review summarizes the theories behind the regulation of zonation, diurnal rhythms and their effect on metabolic zonation, contemporary techniques used to study zonation and current technological challenges, and discusses the current view on spatial and temporal metabolite transport.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370295","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":"p38α kinase governs muscle strength through PGC1α in mice","authors":"Leticia Herrera-Melle,&nbsp;Beatriz Cicuéndez,&nbsp;Juan Antonio López,&nbsp;Phillip A. Dumesic,&nbsp;Sarah E. Wilensky,&nbsp;Elena Rodríguez,&nbsp;Luis Leiva-Vega,&nbsp;Ainoa Caballero,&nbsp;Marta León,&nbsp;Jesús Vázquez,&nbsp;Bruce M. Spiegelman,&nbsp;Cintia Folgueira,&nbsp;Alfonso Mora,&nbsp;Guadalupe Sabio","doi":"10.1111/apha.14234","DOIUrl":"10.1111/apha.14234","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Skeletal muscle, with its remarkable plasticity and dynamic adaptation, serves as a cornerstone of locomotion and metabolic homeostasis in the human body. Muscle tissue, with its extraordinary capacity for force generation and energy expenditure, plays a fundamental role in the movement, metabolism, and overall health. In this context, we sought to determine the role of p38α in mitochondrial metabolism since mitochondrial dynamics play a crucial role in the development of muscle-related diseases that result in muscle weakness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted our study using male mice (MCK-cre, p38α^MCK-KO and PGC1α ^MCK-KO) and mouse primary myoblasts. We analyzed mitochondrial metabolic, physiological parameters as well as proteomics, western blot, RNA-seq analysis from muscle samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings highlight the critical involvement of muscle p38α in the regulation of mitochondrial function, a key determinant of muscle strength. The absence of p38α triggers changes in mitochondrial dynamics through the activation of PGC1α, a central regulator of mitochondrial biogenesis. These results have substantial implications for understanding the complex interplay between p38α kinase, PGC1α activation, and mitochondrial content, thereby enhancing our knowledge in the control of muscle biology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This knowledge holds relevance for conditions associated with muscle weakness, where disruptions in these molecular pathways are frequently implicated in diminishing physical strength. Our research underscores the potential importance of targeting the p38α and PGC1α pathways within muscle, offering promising avenues for the advancement of innovative treatments. Such interventions hold the potential to improve the quality of life for individuals affected by muscle-related diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363544","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}