Peptides最新文献

{"title":"Maximizing cost savings in heart failure management: The economic value of natriuretic peptide testing","authors":"Damien Gruson ,&nbsp;Gaetano Caforio ,&nbsp;Daniel D’Angela","doi":"10.1016/j.peptides.2025.171428","DOIUrl":"10.1016/j.peptides.2025.171428","url":null,"abstract":"<div><div>Heart failure (HF) remains a significant global health challenge, requiring cost-effective strategies to optimize patient outcomes and resource allocation. Natriuretic peptide (NP) testing has demonstrated substantial clinical and economic value in HF diagnosis, risk stratification, and management. This article examines the international evidence supporting NP testing, highlighting its role in reducing hospitalizations, optimizing medication use, and lowering healthcare expenditures. Addressing disparities in access and reimbursement policies can further enhance its adoption and impact across healthcare systems.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171428"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of central UAG on metabolic associated fatty liver disease: A possible mechanism involving in GLP-1 neural pathway","authors":"Wenxiu Xu ,&nbsp;Zixin Du ,&nbsp;Jing Wang ,&nbsp;Yating Gong ,&nbsp;Jiantong Yu ,&nbsp;Xueyuying Wang ,&nbsp;Xiangrong Sun ,&nbsp;Yanling Gong","doi":"10.1016/j.peptides.2025.171427","DOIUrl":"10.1016/j.peptides.2025.171427","url":null,"abstract":"<div><h3>Objective</h3><div>The study aimed to investigate the possible effect of central unacylated ghrelin (UAG) on metabolic associated fatty liver disease (MAFLD) and its underlying mechanism.</div></div><div><h3>Methods</h3><div>A high fat diet (HFD) was fed to rat to construct MAFLD model. UAG was administered via intra-cerebroventricular injection (ICV) and its effect on MAFLD was observed. Glucagon-like peptide-1 (GLP-1) neural pathway was observed via FluoroGold (FG) retrograde tracking combined with immunofluorescence. To assess the involvement of the GLP-1 pathway, GLP-1 receptor (GLP-1R) inhibitor Exendin (9−39) was injected prior to ICV of UAG.</div></div><div><h3>Results</h3><div>ICV administration of UAG significantly reduced lipid accumulation in liver and liver injury in MAFLD rats which was partially attenuated by Exendin(9−39). Central UAG upregulated and activated GLP-1 neurons in nucleus tractus solitarii (NTS), and increased GLP-1 projections from NTS to paraventricular hypothalamic nucleus (PVN) and ventral tegmental area (VTA), respectively. Consequently, GLP-1R in PVN and VTA was activated, resulting in decreased food intake and reward behavior, as well as increased hepatic insulin sensitivity via activation of IRS-1/PI3K/Akt signaling pathway. These changes downregulated key lipogenic enzymes, including fatty acid synthase (FAS), acetyl-CoA Carboxylase (ACC) and stearoyl-CoAdesaturase-1 (SCD-1), thereby alleviating MAFLD.</div></div><div><h3>Conclusion</h3><div>These findings suggest that central UAG might alleviate MAFLD by modulating GLP-1 neuronal pathway from NTS to PVN and VTA. Further studies are needed to identify the specific receptor for UAG and its potential interaction with GLP-1 or GLP-1R, which could provide direct evidence for the role of central UAG in regulating food intake and lipid metabolism in MAFLD.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171427"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of thyrotropin-releasing hormone (TRH) and its receptors (TRHRs) in Nile tilapia: Molecular identification, ligand-receptor interaction and expression profile","authors":"Guixian Bu ,&nbsp;Tao Yong ,&nbsp;Yuqing Tang ,&nbsp;Jingyan Luo ,&nbsp;Yu Ji ,&nbsp;Li Guo ,&nbsp;Shasha Guo ,&nbsp;Shuai Yang ,&nbsp;Linyan Huang ,&nbsp;Xianyin Zeng ,&nbsp;Caiyun Sun ,&nbsp;Fengyan Meng","doi":"10.1016/j.peptides.2025.171426","DOIUrl":"10.1016/j.peptides.2025.171426","url":null,"abstract":"<div><div>Thyrotropin-releasing hormone (TRH) is a highly conserved tripeptide across vertebrates and regulates various biological processes, including energy metabolism, appetite, and reproduction. The functions of TRH are mediated by TRH receptors (TRHRs). In vertebrates, three <em>TRHR</em> subtypes have been identified, namely <em>TRHR1</em>, <em>TRHR2</em>, and <em>TRHR3</em>. However, <em>TRHR2</em> and <em>TRHR3</em> are often lost in some vertebrate lineages, highlighting the evolutionary divergence of the TRH-TRHR system. Although extensive research has been conducted in mammals, studies concerning the biological roles of TRH-TRHR system remain limited in fish. Therefore, using Nile tilapia (ti-) as a teleost model, we cloned the full-length cDNA of <em>TRH</em> and its receptors. Based on sequence alignment, synteny analysis and phylogenetic tree construction, we observed that <em>TRHR2</em> has been lost in Nile tilapia. The cloned <em>tiTRHRs</em> were designated as <em>tiTRHR1a</em>, <em>tiTRHR1b</em>, and <em>tiTRHR3</em>. Using luciferase reporter assays, signal pathway inhibitors and western blot analysis, we demonstrated that tiTRH could effectively activate tiTRHR1a, tiTRHR1b, and tiTRHR3, leading to the stimulation of intracellular calcium mobilization, MAPK/ERK, and cAMP/PKA signaling cascades. However, the efficiencies in activating signaling pathways differed between tiTRHR subtypes upon tiTRH treatment. Quantitative real-time PCR revealed that <em>tiTRH</em> and <em>tiTRHRs</em> were mainly expressed in the central nervous system (CNS) including the hypothalamus. Moreover, hypothalamic mRNA levels of <em>tiTRH</em> and <em>tiTRHR1b</em> were significantly downregulated in response to short-term fasting and acute cold exposure, while <em>tiTRHR1a</em> expression was only responsive to acute cold stress. Collectively, our data will facilitate a better understanding of the components and functions of the TRH-TRHR system in teleost.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171426"},"PeriodicalIF":2.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant production of isotope-labeled human α-defensin 5 via calmodulin fusion and insights into its expression enhancement","authors":"Shaonan Yan ,&nbsp;Hao Gu ,&nbsp;Mitsuki Shibagaki ,&nbsp;Jeremia Oktavian Chrisnanto ,&nbsp;Fumi Hirai ,&nbsp;Hiroyuki Kumeta ,&nbsp;Yasuhiro Kumaki ,&nbsp;Yuki Yokoi ,&nbsp;Kiminori Nakamura ,&nbsp;Takashi Kikukawa ,&nbsp;Tokiyoshi Ayabe ,&nbsp;Tatsuya Arai ,&nbsp;Tomoyasu Aizawa","doi":"10.1016/j.peptides.2025.171425","DOIUrl":"10.1016/j.peptides.2025.171425","url":null,"abstract":"<div><div>Human α-defensin 5 (HD5), a cysteine-rich antimicrobial peptide critical for intestinal innate immunity, has been extensively studied for its structural and functional properties. Both the reduced form (HD5red) and the oxidized form (HD5oxi) exist <em>in vivo</em> and exhibit distinct antimicrobial activity spectra. In this study, we developed an efficient method to overexpress recombinant HD5 in <em>Escherichia coli</em> (<em>E. coli</em>) BL21 (DE3) strain by using calmodulin (CaM), which also interacts with antimicrobial peptides, as a fusion partner. Fusion expression suppressed the degradation of HD5 and reduced its toxicity to host cells. Following purification of the fusion protein and enzymatic cleavage to release the HD5 region, we successfully obtained sufficient amounts (yielding 1.5–1.7 mg/L culture) of active recombinant HD5oxi and HD5red for various applications, including stable isotope-labeled peptides for NMR analysis. Furthermore, we investigated the protective effect of CaM fusion and the mechanism of disulfide bond formation using CD and NMR spectroscopy, structural prediction, and molecular dynamics simulations. Our results suggest that the appropriate interaction strength between CaM and the HD5 region in the fusion state is a key factor for stable production.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171425"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical stretch improves high glucose-induced leptin resistance thus promoting glucose uptake of C2C12 myoblasts","authors":"Shaoting Fu ,&nbsp;Jin Peng ,&nbsp;Xiaohui Wang","doi":"10.1016/j.peptides.2025.171424","DOIUrl":"10.1016/j.peptides.2025.171424","url":null,"abstract":"<div><div>Exercise has been shown to alleviate central leptin resistance (LR), while the effects of exercise on peripheral especially skeletal muscle LR and its mechanisms remain poorly understood. In this study, we explored the effect and mechanisms of mechanical stretch (mimic exercise in vitro) on high glucose-induced LR of C2C12 myoblasts. We found (1) 65 mM glucose-induced LR of C2C12 cells was improved by 15 % stretch lasting for 3 or 6 h (represented as decrease of leptin and increases of leptin receptor (LepR) and glucose uptake), with more glucose uptake in 6h-stretch than 3h-stretch; (2) 15 % stretch changed the levels of important regulators of LR, including increasing signal transducer and activator of transcription 3 (STAT3), decreasing protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling-3 (SOCS3), with higher alterations of STAT3 and SOCS3 in 6h-stretch than 3h-stretch; (3) 15 % stretch activated the classical pathway regulating glucose metabolism, including increasing the levels of insulin-like growth factor (IGF-1), IGF-1 receptor (IGF-1R), insulin receptor substrate 1 (IRS-1), protein kinase B (Akt) and glucose transporter 4 (GLUT4), enhancing activities of phosphoinositide 3-kinase (PI3K) and Akt, with more increases of IGF-1R and IRS1 in 6h-stretch than 3h-stretch and enhanced GLUT4 only in 6h-stretch. Altogether, 15 % stretch alleviated high glucose-induced LR of C2C12 myoblasts through increasing STAT3 and decreasing PTP1B and SOCS3, then enhancing glucose uptake via IGF-1/IGF-1R-PI3K/Akt-GLUT4 pathway, which would deepen our understanding how exercise improved skeletal muscle LR and subsequent glucose uptake.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171424"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of the plant cyclotide cyO14 via the hydrazide strategy and investigation of its antibacterial and insecticidal activities","authors":"Fawei He ,&nbsp;Yunfei Cui ,&nbsp;Xue Tang ,&nbsp;Dongting Zhangsun ,&nbsp;Sulan Luo ,&nbsp;Yong Wu","doi":"10.1016/j.peptides.2025.171423","DOIUrl":"10.1016/j.peptides.2025.171423","url":null,"abstract":"<div><div>The plant cyclotide <strong>cyO14</strong>, a member of the Möbius subfamily, was synthesized using an hydrazide-based strategy, and its antibacterial, insecticidal, and hemolytic activities were investigated. The linear precursor of cyO14 was prepared via solid-phase peptide synthesis (SPPS) on an hydrazide resin, followed by head-to-tail cyclization through an hydrazide-mediated ligation and disulfide bond formation via spontaneous oxidation. The synthesized cyclotide exhibited a structure identical to that of the naturally occurring counterpart. Biological evaluation demonstrated that <strong>cyO14</strong> possessed significant antibacterial activity against <em>Cryptococcus neoformans</em> and <em>Bacillus subtilis</em>, with a minimum inhibitory concentration (MIC) of 1 μM. Mechanistic studies revealed that <strong>cyO14</strong> exerted its antibacterial effects by disrupting bacterial membranes. Moreover, <strong>cyO14</strong> exhibited negligible hemolytic activity (HD₅₀ &gt; 1000 μM), suggesting excellent biocompatibility. In insecticidal assays, <strong>cyO14</strong> effectively inhibited the growth and development of <em>Helicoverpa armigera</em>. These findings indicate that the hydrazide-mediated cyclization strategy is an efficient method for the synthesis of Möbius subfamily cyclotides, and that <strong>cyO14</strong> possesses promising pharmaceutical and agricultural potential due to its potent antibacterial and insecticidal activities coupled with high biological safety.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171423"},"PeriodicalIF":2.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous opiates and behavior: 2024","authors":"Richard J. Bodnar","doi":"10.1016/j.peptides.2025.171422","DOIUrl":"10.1016/j.peptides.2025.171422","url":null,"abstract":"<div><div>This paper is the forty-seventh consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2024 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171422"},"PeriodicalIF":2.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurokinin B is a potential target for treating disruption of intestinal mucosal barrier in acute mechanical intestinal obstruction","authors":"Feifan Wang ,&nbsp;Xia Jiang ,&nbsp;Zifeng Zhao ,&nbsp;Yuanyuan Wang ,&nbsp;Haibo Jiang ,&nbsp;Yingchao Gao ,&nbsp;Haobo Wang ,&nbsp;Zhongxin Li","doi":"10.1016/j.peptides.2025.171419","DOIUrl":"10.1016/j.peptides.2025.171419","url":null,"abstract":"<div><h3>Background</h3><div>The neurokinin-B (NKB)/neurokinin-3-receptor (NK3R) pathway is involved in the inflammatory response. However, its role in the disruption of intestine mucosal barrier during mechanical intestinal obstruction (IO) remains unknown.</div></div><div><h3>Methods</h3><div>We collected serum samples from 30 mechanical IO patients and 30 healthy volunteers and measured the serum levels of NKB, lipopolysaccharide (LPS), diamine oxidase (DAO), and D‑lactate (D‑LA) by using ELISA. We subsequently used a mechanical IO mice model and intraperitoneally injected the mice with NKB (Senktide) and NK3R antagonist (NK3Ra). We used the ELISA to measure the tumor necrosis factor (TNF)-α, interleukin (IL)-6, LPS, DAO, and D-LA serum concentrations in the mice. Hematoxylin-eosin (H&amp;E) staining and transmission electron microscopy (TEM) were used to observe structural changes in the intestinal mucosa. Immunohistochemistry was used to detect the expression of claudin-1, occludin and ZO-1 in intestinal tissues.</div></div><div><h3>Results</h3><div>Serum NKB (75.36 ± 28.67 pg/mL <em>vs.</em> 44.95 ± 16.92 pg/mL) and LPS (7.38 ± 3.63 μg/mL <em>vs.</em> 4.50 ± 2.94 μg/mL) levels were higher in mechanical IO patients than in control people (<em>P</em> &lt; 0.05). We found a positive correlation between serum NKB and LPS levels in mechanical IO patients. The serum LPS concentration in the IO+NKB mice was greater than that in the IO mice (<em>P</em> = 0.001). After the use of NK3Ra, the serum LPS, DAO and D-LA levels decreased (<em>P</em> &lt; 0.05). H&amp;E staining indicated that the intestinal mucosal epithelial structure was severely damaged, including lamina propria hemorrhage, atrophied villi, and inflammatory cell infiltration in IO+NKB mice. TEM revealed that the junctional complexes between epithelial cells were disrupted and absent in the IO+NKB mice. Compared with those in the IO mice, the expression levels of claudin-1 and occludin in intestinal tissues were lower in the IO+NKB mice. However, the intraperitoneal injection of NK3Ra attenuated the damage to tight junction proteins and the intestinal mucosal structure caused by NKB. Additionally, we observed that the serum IL-6 and TNF-α levels in the IO+NK3Ra mice were lower than those in the IO mice (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>NKB might increase the levels of serum IL-6 and TNF-α by acting on the NK3 receptor, promoting intestinal inflammation, and subsequently destroying the intestinal mucosal barrier during mechanical IO.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171419"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole body distribution of the regulatory peptide 26RFa in male and female mice","authors":"Marie Picot ,&nbsp;Mélodie Devère ,&nbsp;Saloua Takhlidjt ,&nbsp;Corentin Guillemot ,&nbsp;Caroline Lusurier ,&nbsp;Gaëtan Prévost ,&nbsp;Nicolas Chartrel ,&nbsp;David Godefroy","doi":"10.1016/j.peptides.2025.171417","DOIUrl":"10.1016/j.peptides.2025.171417","url":null,"abstract":"<div><div>26RFa is a regulatory peptide initially isolated from the brain. 26RFa was found to be involved in the regulation of vital functions such as the regulation of energy and glucose metabolism. However, the whole distribution of 26RFa in the organs/tissues of the organism remains fragmentary although it represents a crucial step to discover novel physiological functions for this regulatory peptide. To this aim, we have generated a mouse line that expresses the fluorescent protein tdTomato in 26RFa-expressing cells, and visualization of tdTomato immunostaining <em>in toto</em> was performed using the tridimensional imaging approach.</div><div>Our observations reveal that 26RFa is largely distributed among the organism of male and female mice. 26RFa-expressing cells were notably found in numerous regions of the central nervous system including the olfactory bulbs, the cortex, the hippocampus, the hypothalamus, the cerebellum, the brainstem and the spinal cord. At the periphery, 26RFa-expressing structures were detected all along the gastrointestinal tract, in the liver, the white adipose tissue, the kidney, the adrenal gland, the lungs, the male and female reproductive tracts, the striated muscles, the thymus and a number of exocrine glands such as the salivary glands, the prostate, the seminal vesicles.</div><div>In conclusion, the present anatomical observations are in agreement with the main physiological functions previously reported for 26RFa such the regulation of energy and glucose metabolism or the control of the hypothalamo-pituitary-gonadal or adrenal axis. However, 26RFa is present in other organs/tissues in which its physiological relevance is totally unknown opening therefore a new field of research for this regulatory peptide.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171417"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF-1 contributes to cardiovascular protection in obesity by upregulating Na+/K+-ATPase activity and modulating key signaling pathways in rats on a high-fat diet","authors":"Katarina Banjac ,&nbsp;Milan Obradovic ,&nbsp;Sonja Zafirovic ,&nbsp;Esma R. Isenovic","doi":"10.1016/j.peptides.2025.171418","DOIUrl":"10.1016/j.peptides.2025.171418","url":null,"abstract":"<div><div>This study examined the ability of insulin-like growth factor-1 (IGF-1) to improve the expression and function of cardiac sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and reduce heart hypertrophy in obese rats. Adult male Wistar rats received a standard diet or a high-fat (HF) diet for 12 weeks. A bolus injection of IGF-1 (50 μg/kg, i.p.) was administered to half of the HF rats 24 hours before euthanasia. IGF-1 treatment increased: the activity of Na⁺/K⁺-ATPase and expression of phosphorylated and total Na⁺/K⁺-ATPase α₁ subunit, the phosphorylation of IGF-1 receptor β /insulin receptor β at Tyr¹¹³¹/Tyr¹¹⁴⁶, insulin receptor substrate-1 (IRS-1) at Tyr¹²²², mammalian target of rapamycin (mTOR) at Ser²⁴⁸¹, protein kinase B (Akt) at Ser⁴⁷³ and the expression of type-2 angiotensin II <em>(</em>AngII) receptor (AT₂R). Conversely, IGF-1 reduced the levels of IRS-1 phosphorylated at Ser³⁰⁷, mTOR at Ser²⁴⁴⁸, ribosomal protein p70 S6 kinase (S6K) at Thr⁴²¹/Ser⁴²⁴, and the expression of type-1 Ang II receptor (AT₁R) in the heart, as well as the serum levels of Ang II in obese rats. IGF-1 treatment reduced cardiac mass and elevated mRNA expression of the α-myosin heavy chain (MHC), and the α/β MHC ratio in the hearts of obese rats. The results of this study suggest that the administration of IGF-1 to obese rats reduces the adverse effects of HF diet, potentially by lowering Ang II-mediated activation of mTOR/S6K and enhancing the IRS-1/Akt pathway, which promotes Na⁺/K⁺-ATPase activity in the heart and diminishes cardiac hypertrophy.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171418"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}