Peptides最新文献

{"title":"R-954, a bradykinin B1 receptor antagonist, as a potential therapy in a preclinical endometriosis model","authors":"Patricia Ribeiro de Carvalho França ,&nbsp;João Pedro Barros de Paiva ,&nbsp;Rosangela Ribeiro de Carvalho ,&nbsp;Claudia Pinto Figueiredo ,&nbsp;Pierre Sirois ,&nbsp;Patricia Dias Fernandes","doi":"10.1016/j.peptides.2024.171294","DOIUrl":"10.1016/j.peptides.2024.171294","url":null,"abstract":"<div><p>Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues outside of the uterine cavity. Currently available drugs are efficacious in treating endometriosis-related pain, however it’s not a targeted treatment. The aim of this work is to evaluate the effects of R-954, a bradykinin B1 receptor antagonist, in a murine model of endometriosis. The model was induced in animals through autologous transplantation of part of the uterine horn. After 51 days, it was observed that implants developed into endometriotic lesions. The administration of R-954 or progesterone, for 15 consecutive days, prevented the progression of cyst development, reduced the size and weight of the cysts. Both treatments also reduced cellular infiltrate and production of inflammatory mediators (interleukin-1β, interleukin-6, tumor necrosis factor). However, only R-954 decreased angiogenic factors (VEGF and VEGF receptor). In addition, treatment with the antagonist did not interfere in the females’ estrous cycle, as well as prevented gestational losses (reduction in the number of intermediate resorptions in pregnant females with endometriosis). Data suggested that R-954 has anti-inflammatory and anti-angiogenic effects; does not influence the estrous cycle; and prevents the number of gestational losses suggesting it as a good candidate for endometriosis treatment.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171294"},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232351","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":"Asprosin-mediated regulation of ovarian functions in mice: An age-dependent study","authors":"Ananya Banerjee ,&nbsp;Vishesh Chauhan ,&nbsp;Anamika ,&nbsp;Mamta Tripathy ,&nbsp;Umesh Rai","doi":"10.1016/j.peptides.2024.171293","DOIUrl":"10.1016/j.peptides.2024.171293","url":null,"abstract":"<div><p>Asprosin is a recently discovered adipokine reported to be involved in the modulation of mammalian gonadal functions. Preliminary investigations suggest its role in regulation of ovarian functions in rodents as well as bovids. In addition, increased levels of the adipokine during human ovarian pathophysiologies implicate it in disease progression and severity. The present study evidenced high expression of asprosin in ovaries of juvenile, pubertal and adult mice while expression was significantly low in ageing ovaries. Further, asprosin stimulated expression of markers for ovarian folliculogenesis (<em>Scf</em>, <em>c-Kit</em>, <em>Gdf9</em>, <em>Bmp6</em>, <em>Fshr</em>, <em>Lhr</em>) and steroidogenesis (<em>3β-Hsd</em>) in adult mice. In addition to exploring concentration-dependent effect of asprosin, the study implicates asprosin as an age-dependent modulator of ovarian functions as treatment of ovaries with asprosin led to upregulation of <em>Fshr</em>, <em>c-Kit</em>, <em>Bmp6</em>, and <em>Gdf9</em> in both adult and juvenile ovaries, <em>Lhr</em> only in adults while that of <em>Scf</em> only in juvenile ovaries. The current study is first to report an age-dependent expression and role of asprosin in murine ovaries.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171293"},"PeriodicalIF":2.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146023","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":"Serum CIAPIN1 is lower in septic patients with cardiac dysfunction","authors":"Nongzhang Xu ,&nbsp;Cuihong Wang ,&nbsp;Jianwei Wan ,&nbsp;Lin Chen","doi":"10.1016/j.peptides.2024.171295","DOIUrl":"10.1016/j.peptides.2024.171295","url":null,"abstract":"<div><p>The study aimed to investigate the clinical significance of serum cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and its potential impact on cardiac dysfunction and inflammatory response induced by sepsis. A cross-sectional study was conducted in an intensive care unit (ICU) involving 80 healthy individuals and 95 severe sepsis patients. The data were analyzed to establish the correlation between CIAPIN1 levels and the onset of cardiac dysfunction in patients with sepsis. The associations have been established by the Pearson correlation test, one-way ANOVA, Bonferroni post hoc test, and plotting the receiver operating characteristic (ROC). H9c2 cells were treated with LPS (1 μg/mL) for 24 h to establish an <em>in vitro</em> model of septic cardiomyopathy. Meanwhile, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). Serum CIAPIN1 levels were considerably lower in sepsis patients with cardiac dysfunction. CIAPIN1 expression levels were negatively correlated with TNF-α (r = −0.476, P&lt;0.001), IL-1β (r = −0.584, P&lt;0.001), IL-6 (r = −0.618, P&lt;0.001), creatine kinase- MB (CK-MB) (r = −0.454, P&lt;0.001), and high-sensitive cardiac troponin T (hs-cTnT) (r = −0.586, P&lt;0.001). The ROC curve showed that CIAPIN1 significantly identify sepsis patients from healthy individuals. CIAPIN1 knockdown decreases cardiomyocyte proliferation and increases apoptosis induced by LPS. In addition, CIAPIN1 knockdown reduced cardiac dysfunction and increased inflammatory response in H9c2 rat cardiomyocytes. CIAPIN1 could be a potential biomarker for detecting sepsis patients and suppressing CIAPIN1 expression in H9c2 rat cardiomyocytes, attenuating sepsis-induced cardiac dysfunction.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171295"},"PeriodicalIF":2.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124001487/pdfft?md5=515696ee0f021d242d6e326dd50e4496&pid=1-s2.0-S0196978124001487-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin-mediated motivated arousal and reward seeking","authors":"Theresa E. Bjorness ,&nbsp;Robert W. Greene","doi":"10.1016/j.peptides.2024.171280","DOIUrl":"10.1016/j.peptides.2024.171280","url":null,"abstract":"<div><p>The neuromodulator orexin has been identified as a key factor for motivated arousal including recent evidence that sleep deprivation-induced enhancement of reward behavior is modulated by orexin. While orexin is not necessary for either reward or arousal behavior, orexin neurons’ broad projections, ability to sense the internal state of the animal, and high plasticity of signaling in response to natural rewards and drugs of abuse may underlie heightened drug seeking, particularly in a subset of highly motivated reward seekers. As such, orexin receptor antagonists have gained deserved attention for putative use in addiction treatments. Ongoing and future clinical trials are expected to identify individuals most likely to benefit from orexin receptor antagonist treatment to promote abstinence, such as those with concurrent sleep disorders or high craving, while attention to methodological considerations will aid interpretation of the numerous preclinical studies investigating disparate aspects of the role of orexin in reward and arousal.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"180 ","pages":"Article 171280"},"PeriodicalIF":2.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004966","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":"Allatotropin (AT) related peptides L-ATRP and D2-ATRP diastereomers activate an endogenous receptor and suppress heart rate in the Pacific abalone Haliotis discus hannai","authors":"Sang Hyuck Lee ,&nbsp;Mi Ae Kim ,&nbsp;Young Chang Sohn","doi":"10.1016/j.peptides.2024.171284","DOIUrl":"10.1016/j.peptides.2024.171284","url":null,"abstract":"<div><p>Allatotropin (AT) has been identified in many insects and plays important roles in the regulation of their intestinal contraction, heart rate, ion transport, and digestive enzyme secretion. However, information on AT-related bioinformatics in other animal phyla is scarce. In this study, we cloned a full-length cDNA encoding the AT-related peptide receptor (ATRPR) of the abalone <em>Haliotis discus hannai</em> (Hdh) and further characterized Hdh-ATRPR with its potential ligands, Hdh-ATRPs. In luciferase reporter and Ca²⁺ mobilization assays, Hdh-ATRPs, including a D-type Phe at the second amino acid position, Hdh-D2-ATRP, activated Hdh-ATRPR in a dose-dependent manner, whereas all-L-type Hdh-ATRP was a more potent ligand than Hdh-D2-ATRP. Furthermore, Hdh-ATRPs induced ERK1/2 phosphorylation in Hdh-ATRPR-expressing HEK293 cells, which was dose-dependently abolished by the PKC inhibitor Gö6983. The heart rate decreased significantly within 10 min when Hdh-D2-ATRP was injected into the adduct muscle sinus of abalone (0.2 or 1.0 µg/g body weight), while the abalone injected with a high concentration of Hdh-D2-ATRP (1.5 μg/g body weight) were sublethal within 5 h. Thus, Hdh-ATRP signaling is primarily linked to the Gαq/PKC and is possibly associated with heart rate regulation in abalone.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171284"},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988562","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":"Role of sexually dimorphic oxytocin receptor-expressing neurons in the anteroventral periventricular nucleus on maternal behavior","authors":"Ryoichi Teruyama,&nbsp;Armita A. Govar","doi":"10.1016/j.peptides.2024.171283","DOIUrl":"10.1016/j.peptides.2024.171283","url":null,"abstract":"<div><p>Oxytocin is a neuropeptide produced by magnocellular neurosecretory neurons located primarily in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. The long axons of these neurons project to the neurohypophysis where oxytocin is released into the general circulation in response to the physiological demands. Oxytocin plays critical roles in female reproductive physiology, specifically in uterine contraction during labor and milk ejection while nursing. Oxytocin is also called \"the love hormone\" due to its modulatory roles in prosocial behaviors, including social recognition, maternal behavior, and pair bonding. Oxytocin influences behaviors by binding to oxytocin receptors (OXTR) located in various parts of the brain. Previously, we discovered a group of estrogen-dependent OXTR neurons that is exclusively present in the anteroventral periventricular nucleus (AVPV) of females but not of males. The female-specific expression of OXTR in the AVPV is a rare case of neurochemically-demonstrated, all-or-none sexual dimorphism in the brain. In this review, the cellular characterization and functional significance of the sexually dimorphic OXTR neurons in the AVPV as well as the clinical implications of the research will be discussed.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"180 ","pages":"Article 171283"},"PeriodicalIF":2.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982953","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":"Isolation and characterization of NGFFYamide neuropeptide from Patiria pectinifera pyloric caeca extract","authors":"Anastasia Kubarova ,&nbsp;Hye-Jin Go ,&nbsp;Hye Young Oh ,&nbsp;Soohyun Park ,&nbsp;Hyun-Myoung Oh ,&nbsp;Nam Gyu Park","doi":"10.1016/j.peptides.2024.171282","DOIUrl":"10.1016/j.peptides.2024.171282","url":null,"abstract":"<div><p>Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (<em>Patiria pectinifera</em>) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an <em>in vitro</em> bioassay to screen for fractions and peptides with relaxing effects on <em>P. pectinifera</em> apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from <em>P. pectinifera</em> through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. <em>In vitro</em> pharmacological studies on muscle preparations from <em>P. pectinifera</em> and <em>Asterias amurensis</em> revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in <em>P. pectinifera</em> cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on <em>P. pectinifera</em> cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in <em>P. pectinifera</em> apical muscle but not in <em>A. amurensis</em>, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in <em>P. pectinifera</em>, consistent with findings in <em>Asterias rubens</em>.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"180 ","pages":"Article 171282"},"PeriodicalIF":2.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971607","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":"Systemic and tissue-specific spexin response to acute treadmill exercise in rats","authors":"Ibrahim Turkel ,&nbsp;Berkay Ozerklig ,&nbsp;Burak Yazgan ,&nbsp;Ahmet Emrah Ozenc ,&nbsp;Gokhan Burcin Kubat ,&nbsp;Gulcin Simsek ,&nbsp;Muhammed Mustafa Atakan ,&nbsp;Sukran Nazan Kosar","doi":"10.1016/j.peptides.2024.171281","DOIUrl":"10.1016/j.peptides.2024.171281","url":null,"abstract":"<div><p>Spexin (SPX) is a 14-amino-acid peptide that plays an important role in the regulation of metabolism and energy homeostasis. It is well known that a variety of bioactive molecules released into the circulation by organs and tissues in response to acute and chronic exercise, known as exerkines, mediate the benefits of exercise by improving metabolic health. However, it is unclear whether acute exercise affects SPX levels in the circulation and peripheral tissues. This study aimed to determine whether acute treadmill exercise induces plasma SPX levels, as well as mRNA expression and immunostaining of SPX in skeletal muscle, adipose tissue, and liver. Male Sprague Dawley rats were divided into sedentary and acute exercise groups. Plasma, soleus (SOL), extensor digitorum longus (EDL), adipose tissue, and liver samples were collected at six time points (0, 1, 3, 6, 12, and 24 h) following 60 min of acute treadmill exercise at a speed of 25 m/min and 0 % grade. Acute exercise increased plasma SPX levels and induced mRNA expression of <em>Spx</em> in the SOL, EDL, and liver. Immunohistochemical analysis demonstrated that acute exercise led to a decrease in SPX immunostaining in the liver. Taken together, these findings suggest that SPX increases in response to acute exercise as a potential exerkine candidate, and the liver may be one of the sources of acute exercise-induced plasma SPX levels in rats. However, a comprehensive analysis is needed to fully elucidate the systemic response of SPX to acute exercise, as well as the tissue from which SPX is secreted.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"180 ","pages":"Article 171281"},"PeriodicalIF":2.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902580","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":"Bombesin protects myocardium against ischemia/reperfusion injury via activation of the Keap1-Nrf2-HO-1 signaling pathway","authors":"Jinyi Zhang ,&nbsp;Yanhuan Du ,&nbsp;Zhenyu Xiong ,&nbsp;Hang Cheng ,&nbsp;Yi Du ,&nbsp;Yulian Xiong ,&nbsp;Jianfeng Lv ,&nbsp;Wenquan Huang ,&nbsp;Kuncheng Qiu ,&nbsp;Shizhong Zhang","doi":"10.1016/j.peptides.2024.171279","DOIUrl":"10.1016/j.peptides.2024.171279","url":null,"abstract":"<div><h3>Aims</h3><p>It has been reported that some peptides released by the gastro-intestinal tract play important roles in the prevention of myocardial ischemia/reperfusion injury (MIRI). Bombesin (BN) is a biologically active peptide released by non-adrenergic non-cholinergic nerves on the gastric antrum mucosa controlled by the vagus nerve. However, there is a lack of reports on the impact of BN on MIRI. This study aimed to explore the influence of BN on MIRI and its underlying mechanism.</p></div><div><h3>Materials and methods</h3><p>MIRI was induced by either 30 min of global ischemia in Langendorff perfused rat hearts, or by ligation of the descending coronary artery for 30 min in anesthetized Spraque-Dawley rats, and both were followed by 120 min reperfusion. Infarct size and left ventricular function were assessed, and lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels were measured spectrophotometrically, while cardiomyocyte apoptosis was detected by TUNEL assay. The content of BN in plasma was measured with enzyme-linked immunosorbent assays (ELISA). The expression of caspase 3, Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were quantified.</p></div><div><h3>Key findings</h3><p>BN and vagus nerve stimulation improved cardiac contractile function and reduced myocardial infarct size, attenuated oxidative stress damage and myocardial cell apoptosis, increased the expression of Keap1, Nrf2, and HO-1. and these effects were blocked by using a BN receptor antagonist.</p></div><div><h3>Significance</h3><p>BN provides protection against MIRI, and its underlying mechanism is through activation of the Keap1/Nrf2/HO-1 pathway. This research provides more reliable evidence for the \"gut-heart axis dialogue\" and explores potential therapeutic approaches for MIRI.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"180 ","pages":"Article 171279"},"PeriodicalIF":2.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760251","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":"Tirzepatide shows neuroprotective effects via regulating brain glucose metabolism in APP/PS1 mice","authors":"Shaobin Yang,&nbsp;Xiaoqian Zhao,&nbsp;Yimeng Zhang,&nbsp;Qi Tang,&nbsp;Yanhong Li,&nbsp;Yaqin Du,&nbsp;Peng yu","doi":"10.1016/j.peptides.2024.171271","DOIUrl":"10.1016/j.peptides.2024.171271","url":null,"abstract":"<div><p>Tirzepatide (LY3298176), a GLP-1 and GIP receptor agonist, is fatty-acid-modified and 39-amino acid linear peptide, which ameliorates learning and memory impairment in diabetic rats. However, the specific molecular mechanism remains unknown. In the present study, we investigated the role of tirzepatide in the neuroprotective effects in Alzheimer's disease (AD) model mice. Tirzepatide was administrated intraperitoneal (i.p.) APP/PS1 mice for 8 weeks with at 10 nmol/kg once-weekly, it significantly decreased the levels of GLP-1R, and GFAP protein expression and amyloid plaques in the cortex, it also lowered neuronal apoptosis induced by amyloid-β (Aβ), but did not affect the anxiety and cognitive function in APP/PS1 mice. Moreover, tirzepatide reduced the blood glucose levels and increased the mRNA expression of GLP-1R, SACF1, ATF4, Glu2A, and Glu2B in the hypothalamus of APP/PS1 mice. Tirzepatide increased the mRNA expression of glucose transporter 1, hexokinase, glucose-6-phosphate dehydrogenase, and phosphofructokinase in the cortex. Lastly, tirzepatide improved the energetic metabolism by regulated reactive oxygen species production and mitochondrial membrane potential caused by Aβ, thereby decreasing mitochondrial function and ATP levels in astrocytes through GLP-1R. These results provide valuable insights into the mechanism of brain glucose metabolism and mitochondrial function of tirzepatide, presenting potential strategies for AD treatment.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"179 ","pages":"Article 171271"},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603924","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}