Acta Physiologica最新文献

{"title":"Amiloride versus furosemide for the treatment of edema in patients with nephrotic syndrome: A pilot study (AMILOR)","authors":"Anja Schork,&nbsp;Elisabeth Vogel,&nbsp;Bernhard N. Bohnert,&nbsp;Daniel Essigke,&nbsp;Matthias Wörn,&nbsp;Imma Fischer,&nbsp;Nils Heyne,&nbsp;Andreas L. Birkenfeld,&nbsp;Ferruh Artunc","doi":"10.1111/apha.14183","DOIUrl":"10.1111/apha.14183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. However, apart from case reports, there is no evidence favoring ENaC blockade in patients with NS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amiloride (starting dose 5 mg/day, max. 15 mg/day) in comparison to standard therapy with the loop diuretic furosemide (40 mg/day, max. 120 mg/day) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (BCM, Fresenius). Depending on the OH response, diuretic dose was adjusted on days 2, 5, 8 and 12, and if necessary, hydrochlorothiazide (HCT) was added from d8 (12.5 mg/day, max. 25 mg/day). The primary endpoint was the decrease in OH on d8. The study was terminated prematurely due to insufficient recruitment and a low statistical power due to a low actual effect size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median baseline OH was +26.4 (interquartile range 15.5–35.1)% extracellular water (ECW) in the amiloride arm and + 27.9 (24.1–29.4)% ECW in the furosemide arm and decreased by 1.95 (0.80–6.40) and 5.15 (0.90–8.30)% ECW after 8 days, respectively, and by 10.10 (1.30–14.40) and 7.40 (2.80–10.10)% ECW after 16 days, respectively. OH decrease on d8 and d16 was not significantly different between both arms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AMILOR study is the first randomized controlled pilot study suggesting a similar antiedematous effect as furosemide. Further studies are required to better define the role of amiloride in NS (EudraCT 2019-002607-18).</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185527","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":"ANXA1sp modulates the protective effect of Sirt3-induced mitophagy against sepsis-induced myocardial injury in mice","authors":"Wanyu Ma,&nbsp;Zhijia Huang,&nbsp;Yanmei Miao,&nbsp;Xinglong Ma,&nbsp;Zhiquan Zhang,&nbsp;Wenjie Liu,&nbsp;Peng Xie","doi":"10.1111/apha.14184","DOIUrl":"10.1111/apha.14184","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sepsis-induced myocardial injury (SIMI) may be associated with insufficient mitophagy in cardiomyocytes, but the exact mechanism involved remains unknown. Sirtuin 3 (Sirt3) is mainly found in the mitochondrial matrix and is involved in repairing mitochondrial function through means such as the activation of autophagy. Previously, we demonstrated that the annexin-A1 small peptide (ANXA1sp) can promote Sirt3 expression in mitochondria. In this study, we hypothesized that the activation of Sirt3 by ANXA1sp induces mitophagy, thereby providing a protective effect against SIMI in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A mouse model of SIMI was established via cecal ligation and puncture. Intraperitoneal injections of ANXA1sp, 3TYP, and 3MA were administered prior to modeling. After successful modeling, IL-6, TNF-α, CK-MB, and CTn-I levels were measured; cardiac function was assessed using echocardiography; myocardial mitochondrial membrane potential, ROS, and ATP production were determined; myocardial mitochondrial ultrastructure was observed using transmission electron microscopy; and the expression levels of Sirt3 and autophagy-related proteins were detected using western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ANXA1sp significantly reduced serum IL-6, TNF-α, CK-MB, and CTn-I levels; decreased myocardial ROS production; increased mitochondrial membrane potential and ATP synthesis; and improved myocardial mitochondrial ultrastructure in septic mice. Furthermore, ANXA1sp promoted Sirt3 expression and activated the AMPK-mTOR pathway to induce myocardial mitophagy. These protective effects of ANXA1sp were reversed upon treatment with the Sirt3 blocker, 3-TYP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ANXA1sp can reverse SIMI, and the underlying mechanism may be related to the activation of the AMPK-mTOR pathway following upregulation of Sirt3 by ANXA1sp, which, in turn, induces autophagy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185528","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":"Reframing acute kidney injury as a pathophysiological continuum of disrupted renal excretory function","authors":"Neil G. Docherty,&nbsp;Christian Delles,&nbsp;Francisco J. López-Hernández","doi":"10.1111/apha.14181","DOIUrl":"10.1111/apha.14181","url":null,"abstract":"<p>Surrogate measures of glomerular filtration rate (GFR) continue to serve as pivotal determinants of the incidence, severity, and management of acute kidney injury (AKI), as well as the primary reference point underpinning knowledge of its pathophysiology. However, several clinically important deficits in aspects of renal excretory function during AKI other than GFR decline, including acid–base regulation, electrolyte and water balance, and urinary concentrating capacity, can evade detection when diagnostic criteria are built around purely GFR-based assessments. The use of putative markers of tubular injury to detect “sub-clinical” AKI has been proposed to expand the definition and diagnostic criteria for AKI, but their diagnostic performance is curtailed by ambiguity with respect to their biological meaning and context specificity. Efforts to devise new holistic assessments of overall renal functional compromise in AKI would foster the capacity to better personalize patient care by replacing biomarker threshold-based diagnostic criteria with a shift to assessment of compromise along a pathophysiological continuum. The term AKI refers to a syndrome of sudden renal deterioration, the severity of which is classified by precise diagnostic criteria that have unquestionable utility in patient management as well as blatant limitations. Particularly, the absence of an explicit pathophysiological definition of AKI curtails further scientific development and clinical handling, entrapping the field within its present narrow GFR-based view. A refreshed approach based on a more holistic consideration of renal functional impairment in AKI as the basis for a new diagnostic concept that reaches beyond the boundaries imposed by the current GFR threshold-based classification of AKI, capturing broader aspects of pathogenesis, could enhance AKI prevention strategies and improve AKI patient outcome and prognosis.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159882","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":"MicroRNA 29 modulates β-cell mitochondrial metabolism and insulin secretion via underlying miR-29-OXPHOS complex pathways","authors":"E. Cowan,&nbsp;J. Sun,&nbsp;A. Hamilton,&nbsp;S. Ruhrmann,&nbsp;A. Karagiannopoulos,&nbsp;E. Westholm,&nbsp;J. K. Ofori,&nbsp;C. Luan,&nbsp;E. Zhang,&nbsp;H. Mulder,&nbsp;L. Eliasson","doi":"10.1111/apha.14180","DOIUrl":"10.1111/apha.14180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>MicroRNAs (miRNAs) regulate β-cell function, and β-cell mitochondria and insulin secretion are perturbed in diabetes. We aimed to identify key miRNAs regulating β-cell mitochondrial metabolism and novel β-cell miRNA-mitochondrial pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TargetScan (http://www.targetscan.org/) was used to predict if 16 miRNAs implicated in β-cell function target 27 cis-eGenes implicated in mitochondrial activity. The expression of candidate miRNAs and insulin secretion after 24 and 1 h pre-incubation in 2.8, 11.1- and 16.7-mM glucose was measured in clonal INS-1 832/13 β-cells. MiR-29 silenced INS-1 832/13 cells were assessed for insulin secretion (glucose, pyruvate, and K⁺), target cis-eGene expression (<i>Ndufv3</i> and <i>Ndufa10</i> components of mitochondrial complex I (CI)), OXPHOS (CI-V) protein expression, and mitochondrial OXPHOS respiration/activity. The expression of differentially expressed miR-29 miRNAs was evaluated in Goto-Kakizaki (GK) rat, db/db mouse and type 2 diabetic (T2D) human islets, as well as NMRI mouse islets cultured under glucolipotoxic conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MiR-29, miR-15 and miR-124 were predicted to regulate ~20 cis-eGenes, while miR-29 alone was predicted to regulate ≥12 of these in rat and human species. MiR-29 expression and insulin secretion were reduced in INS-1 832/13 cells after 24 h in elevated glucose. MiR-29 knockdown increased all tested insulin secretory responses, <i>Nudfv3</i>, <i>Ndufa10</i>, complex I and II expression, and cellular mitochondrial OXPHOS. MiR-29 expression was reduced in db/db islets but increased in GK rat and T2D human islets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude miR-29 is a key miRNA in regulating β-cell mitochondrial metabolism and insulin secretion via underlying miR-29-OXPHOS complex pathways. Furthermore, we infer reduced miR-29 expression compensatorily enhances insulin secretion under glucotoxicity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154126","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":"Color in physiology","authors":"Pontus B. Persson,&nbsp;Anja Bondke Persson","doi":"10.1111/apha.14182","DOIUrl":"10.1111/apha.14182","url":null,"abstract":"&lt;p&gt;As humans, we detect and process external stimuli through sensory perception.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Vision, scent, touch, sound, and taste, often in combination and/or simultaneously, help us interpret and adequately react to our environments. Sensory and perceptual alterations in humans occur on a wide spectrum,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; ranging from physiological phenomena in response to everyday environmental&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; or hormonal&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; influences, to the aura symptoms in migraine patients, to severe, prolonged alterations that qualify as hallucinations.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Color perception is a fundamental aspect of the human experience. Colors, manifestations of different wavelengths of light, influence human emotions, behaviors and physiological responses.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; From the vibrant hues of a sunset to the subtle shades of a painting, the way we perceive color plays a huge role in shaping our understanding of the world around us. In recent years, scientific inquiry into the details of the mechanisms behind visual perception have deepened our comprehension of how our visual system processes and interprets the rich array of colors in our environment. Recent insights into visual perception and signal interpretation include for example the role of pacsin proteins in vision, a novel function of these regulators of the actin cytoskeleton and cellular transport processes.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Also, in the context of visual perception and the role of visual stimuli in maintaining healthy circadian rhythms, the influence of an impaired eyesight&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; and the role of the eye as not only a light- but also temperature-sensitive organ&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt; have been described.&lt;/p&gt;&lt;p&gt;Aside from human perception and interpretation of light of different wavelenghths as color, colored light has become an indispensable methodological tool for physiologists to precisely manipulate light to activate or inhibit intracerebral neural circuits to selectively stimulate or suppress neuronal activity with high temporal and spatial precision, to e.g. analyze complex neural networks and elucidate causal relationships between neuronal activity and behavior.&lt;span&gt;&lt;sup&gt;11-13&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;However, color is also a multifaceted communicative tool across various domains, encompassing fields from biology to design. In nature, colors often act as a visual language, signaling vital information, for example survival and reproduction. From the vibrant hues of flowers attracting pollinators to the warning colors of venomous creatures, organisms utilize color to convey messages efficiently. Beyond biology, humans harness color as a potent means of expression and communication. Color plays, for example, a pivotal role in branding, where shades become synonymous with companies and products and influence consumer perception and behavior. Color choices evoke emotions, convey cultural sig","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086207","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":"Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer","authors":"Henning Tim Langer,&nbsp;Shakti Ramsamooj,&nbsp;Ezequiel Dantas,&nbsp;Anirudh Murthy,&nbsp;Mujmmail Ahmed,&nbsp;Tanvir Ahmed,&nbsp;Seo-Kyoung Hwang,&nbsp;Rahul Grover,&nbsp;Rita Pozovskiy,&nbsp;Roger J. Liang,&nbsp;Andre Lima Queiroz,&nbsp;Justin C. Brown,&nbsp;Eileen P. White,&nbsp;Tobias Janowitz,&nbsp;Marcus D. Goncalves","doi":"10.1111/apha.14167","DOIUrl":"10.1111/apha.14167","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate systemic regulators of the cancer-associated cachexia syndrome (CACS) in a pre-clinical model for lung cancer with the goal to identify therapeutic targets for tissue wasting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the Kras/Lkb1 (KL) mouse model, we found that CACS is associated with white adipose tissue (WAT) dysfunction that directly affects skeletal muscle homeostasis. WAT transcriptomes showed evidence of reduced adipogenesis, and, in agreement, we found low levels of circulating adiponectin. To preserve adipogenesis and restore adiponectin levels, we treated mice with the PPAR-γ agonist, rosiglitazone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Rosiglitazone treatment increased serum adiponectin levels, delayed weight loss, and preserved skeletal muscle and adipose tissue mass, as compared to vehicle-treated mice. The preservation of muscle mass with rosiglitazone was associated with increases in AMPK and AKT activity. Similarly, activation of the adiponectin receptors in muscle cells increased AMPK activity, anabolic signaling, and protein synthesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data suggest that PPAR-γ agonists may be a useful adjuvant therapy to preserve tissue mass in lung cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079904","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":"Beyond blood pressure, fluid and electrolyte homeostasis – Role of the renin angiotensin aldosterone system in the interplay between metabolic diseases and breast cancer","authors":"Nishan Sudheera Kalupahana,&nbsp;Naima Moustaid-Moussa","doi":"10.1111/apha.14164","DOIUrl":"10.1111/apha.14164","url":null,"abstract":"<p>The classical renin angiotensin aldosterone system (RAAS), as well as the recently described counter-regulatory or non-canonical RAAS have been well characterized for their role in cardiovascular homeostasis. Moreover, extensive research has been conducted over the past decades on both paracrine and the endocrine roles of local RAAS in various metabolic regulations and in chronic diseases. Clinical evidence from patients on RAAS blockers as well as pre-clinical studies using rodent models of genetic manipulations of RAAS genes documented that this system may play important roles in the interplay between metabolic diseases and cancer, namely breast cancer. Some of these studies suggest potential therapeutic applications and repurposing of RAAS inhibitors for these diseases. In this review, we discuss the mechanisms by which RAAS is involved in the pathogenesis of metabolic diseases such as obesity and type-2 diabetes as well as the role of this system in the initiation, expansion and/or progression of breast cancer, especially in the context of metabolic diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069840","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":"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}