Peptides最新文献

{"title":"A murine model of obesity with hyperinsulinemia and hepatic steatosis involving neurosecretory protein GL gene and a low-fat/medium-sucrose diet","authors":"Yuki Narimatsu ,&nbsp;Masaki Kato ,&nbsp;Eiko Iwakoshi-Ukena,&nbsp;Megumi Furumitsu,&nbsp;Kazuyoshi Ukena","doi":"10.1016/j.peptides.2025.171376","DOIUrl":"10.1016/j.peptides.2025.171376","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) featuring hepatic steatosis and insulin dysregulation is becoming a common cause of chronic hepatic diseases. Although the involvement of endocrine disruption in the onset and progression of MASLD is thought to be critical, there are limited effective animal models reflecting hyperinsulinemia and hepatic steatosis. Here, we propose a MASLD mouse model that combines neuropeptide effects and dietary nutrition. We employed chronic overexpression of the gene encoding neurosecretory protein GL (NPGL) in the hypothalamus of ICR mice under a low-fat/medium-sucrose diet (LFMSD). <em>Npgl</em> overexpression promoted fat accumulation in the white adipose tissues in 2 weeks. Basal insulin levels were increased and pancreatic islets expanded following <em>Npgl</em> overexpression. Histological and molecular biological approaches revealed that <em>Npgl</em> overexpression enhanced de novo lipogenesis, leading to hepatic steatosis. Nine-week overexpression of <em>Npgl</em> exacerbated obesity and hyperinsulinemia, resulting in hyperglycemia. Moreover, prolonged <em>Npgl</em> overexpression aggravated fat accumulation in the liver with a change in the lipid metabolic pathway. These findings suggest that <em>Npgl</em> overexpression readily leads to obesity with hyperinsulinemia and hepatic steatosis in ICR mice under an LFMSD.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"186 ","pages":"Article 171376"},"PeriodicalIF":2.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493201","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":"Cholecystokinin - portrayal of an unfolding peptide messenger system","authors":"Jens F. Rehfeld","doi":"10.1016/j.peptides.2025.171369","DOIUrl":"10.1016/j.peptides.2025.171369","url":null,"abstract":"<div><div>This review describes how the classic gut hormone, cholecystokinin (CCK), should be comprehended in 2025. In the early physiological tradition of studying gastrointestinal hormones, the hormones were named after the function that lead to their discovery. Hence, in 1928, the hormonal factor in the upper gut that regulated gallbladder contraction was called cholecystokinin. In 1968, Viktor Mutt and Erik Jorpes identified the porcine structure of this factor as an O-sulfated and carboxyamidated peptide of 33 amino acid residues (CCK-33). Its C-terminal bioactive heptapeptide amide turned out to be homologous to that of the antral hormone, gastrin. The structure allowed <em>in vitro</em> synthesis of peptide fragments for physiological studies and for production of CCK-antibodies for immunoassays and immunohistochemistry. Today, these tools have revealed CCK to be highly complex: CCK is a heterogenous, multifunctional peptide messenger system, widely expressed both in and outside the gut. Thus, the CCK gene encodes six different bioactive peptides (CCK-83, −58, −33, −22, −8, and −5) that are expressed in a cell-specific manner in O-sulfated and non-sulfated forms. Moreover, CCK peptides are not only hormones. They are also potent neurotransmitters, paracrine growth and satiety factors, anti-inflammatory cytokines, incretins, potential fertility factors and useful tumor-markers. Moreover, CCK has a phylogenetic history of nearly 600 million years. Particular interest has been given to the neuroscience of CCK, because CCK is the predominant peptide transmitter in the brain, expressed in amounts that surpass any other neuropeptide. Vice versa, the brain is the main production site of CCK in mammals.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"186 ","pages":"Article 171369"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454816","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":"Erythropoietin improves spatial and nonspatial memory defects by suppressing oxidative damage, inflammation and apoptosis against ethanol neurotoxicity in the developing male rat hippocampus","authors":"Raheleh Rafaiee ,&nbsp;Fahimeh Mohseni ,&nbsp;Mehdi khaksari ,&nbsp;Behzad Garmabi ,&nbsp;Alireza Masoudi ,&nbsp;Zhaleh Jamali ,&nbsp;Shima Mohammadi ,&nbsp;Alieh Bashghareh","doi":"10.1016/j.peptides.2025.171368","DOIUrl":"10.1016/j.peptides.2025.171368","url":null,"abstract":"<div><div>Excessive prenatal exposure to ethanol leads to a condition called fetal alcohol spectrum disorder (FASD). The neurotoxicity of alcohol causes changes in the hippocampus of animals during this time, resulting in impaired hippocampus-related functions, including memory/learning and cognition.The liver and kidneys produce erythropoietin (EPO). The synthesis of EPO by immature neurons also plays a decisive role in the embryonic stage. Also, exogenous EPO exerts its neurocognitive effects in the developing brain under pathophysiological conditions. The aim of this study was to investigate the protective effects of EPO administration after ethanol-induced increased neurodevelopmental toxicity. Male Wistar rat pups were intubated with a dose of 5/27 g/kg/day ethanol from postnatal day 2–10, similar to the last trimester of gestation in humans. Immediately thereafter, EPO (1000 /2000 U/kg, s.c.) were injected. Spatial memory was tested with the Morris water maze (days 36–40) and non-spatial recognition memory with the novel object task (days 39–40). Concentrations of antioxidant enzymes and TNF-α (ELISA) and caspase-3 (immunohistochemical staining) was then performed. The current study shows that EPO administration significantly attenuates spatial and nonspatial memory impairment (P &lt; 0.001). EPO dramatically decreased the amount of caspase 3 positive cells in the CA1 area of the hippocampus (P &lt; 0.01). EPO increased total superoxide dismutase activity (P &lt; 0.05), glutathione concentrations (P &lt; 0.05) and catalase levels (P &lt; 0.001). EPO also attenuated the production of TNF-α and malondialdehyde (P &lt; 0.05). Given EPO's protective effect against ethanol-induced increased neurotoxicity, it is a viable treatment option for FASD, although more research is needed.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"186 ","pages":"Article 171368"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463490","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":"The role of leptin and ghrelin in the regulation of appetite in obesity","authors":"Kinga Skoracka ,&nbsp;Szymon Hryhorowicz ,&nbsp;Piotr Schulz ,&nbsp;Agnieszka Zawada ,&nbsp;Alicja Ewa Ratajczak-Pawłowska ,&nbsp;Anna Maria Rychter ,&nbsp;Ryszard Słomski ,&nbsp;Agnieszka Dobrowolska ,&nbsp;Iwona Krela-Kaźmierczak","doi":"10.1016/j.peptides.2025.171367","DOIUrl":"10.1016/j.peptides.2025.171367","url":null,"abstract":"<div><div>Leptin and ghrelin are two key hormones that play opposing roles in the regulation of appetite and energy balance. Ghrelin stimulates appetite and food intake following binding to receptors and the subsequent activation of orexigenic neurons in the arcuate nucleus. Leptin, conversely, has been demonstrated to suppress appetite and reduce food intake. This occurs through the inhibition of ghrelin-activated neurons, while simultaneously activating those that promote satiety and increase energy expenditure. A lack of biological response despite elevated leptin levels, which is known as leptin resistance, is observed in individuals with excess body weight and represents a significant challenge. As the dysregulation of ghrelin and leptin signalling has been linked to the development of obesity and other metabolic disorders, an in-depth understanding of the genetic determinants affecting these two hormones may facilitate a more comprehensive grasp of the intricate interactions that underpin the pathogenesis of obesity.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"186 ","pages":"Article 171367"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464091","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":"Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice","authors":"Liuqing Xi ,&nbsp;Juan Du ,&nbsp;Yan Lu ,&nbsp;Wen Xue ,&nbsp;Yuxuan Xia ,&nbsp;Tingxu Chen ,&nbsp;Yang Xiao ,&nbsp;Nuo Xu ,&nbsp;Yansheng Wang ,&nbsp;Jianfang Gao ,&nbsp;Wenyi Li ,&nbsp;Shan Huang","doi":"10.1016/j.peptides.2025.171366","DOIUrl":"10.1016/j.peptides.2025.171366","url":null,"abstract":"<div><div>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are frequently utilized to treat type 2 diabetes mellitus (T2DM). Several GLP-1RAs (Exendin-4 and liraglutide) have been shown to accelerate diabetic wound healing. The major aim of the study was to investigate the roles of dulaglutide in wound healing in diabetic mice and identify the underlying mechanism involved. Round-shape, full-thickness wounds were created on the backs of <em>db</em>/<em>db</em> diabetic mice. Subsequently, dulaglutide was delivered via subcutaneous injections surrounding the wound’s perimeter, and the wound closure rates were monitored. <em>In vitro</em>, keratinocytes were treated with dulaglutide under high glucose (HG) conditions, and cell viability was assessed by cell counting kit-8 (CCK-8) and EdU assays. The roles of dulaglutide in ferroptosis were assessed by measuring the levels of Fe^2 + and oxidative stress, as well as the expression of ferroptosis markers. The results demonstrated that dulaglutide treatment increased the expression of vascular endothelial growth factor (VEGF) and the proliferation marker Ki67, thereby accelerating wound healing in diabetic mice. <em>In vitro</em>, dulaglutide promoted HaCaT cell proliferation and migration under HG conditions. Exposure of HaCaT cells to HG resulted in ferroptosis <em>in vivo</em> and <em>in vitro</em>, as evidenced by the significant increase in Fe²⁺, reactive oxygen species (ROS), and malondialdehyde (MDA) levels and the decrease in glutathione (GSH) and superoxide dismutase (SOD) levels. All these effects were reversed by dulaglutide. Mechanistically, dulaglutide activated NFE2-related factor 2 (Nrf2) signaling under HG conditions, which increased glutathione peroxidase (Gpx4) and solute carrier family 7-member 11 (Slc7a11) expression, thereby inhibiting ferroptosis. In summary, these results demonstrate dulaglutide as a promising agent for treating diabetic wounds by regulating Nrf2-dependent ferroptosis.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"185 ","pages":"Article 171366"},"PeriodicalIF":2.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425934","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":"The intricate relationship between circadian rhythms and gastrointestinal peptides in obesity","authors":"Filipe M. Ribeiro ,&nbsp;Luiz Arnaldo ,&nbsp;Lana P. Milhomem ,&nbsp;Samuel S. Aguiar ,&nbsp;Octavio L. Franco","doi":"10.1016/j.peptides.2025.171356","DOIUrl":"10.1016/j.peptides.2025.171356","url":null,"abstract":"<div><div>There are different molecular pathways that regulate appetite, particularly the role of the hypothalamus, circadian rhythms, and gastrointestinal peptides. The hypothalamus integrates signals from orexigenic peptides like neuropeptide Y (NPY) and agouti-related protein (AgRP), which stimulate appetite, and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), which promote satiety. These signals are influenced by peripheral hormones like leptin, ghrelin, insulin, and cortisol, as well as gut peptides including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK). The circadian rhythm, regulated by proteins like circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1), modulates the secretion of these peptides, aligning feeding behaviors with the sleep-wake cycle. In obesity, these regulatory systems are disrupted, leading to leptin resistance, increased ghrelin sensitivity, and altered gut peptide secretion. This results in heightened appetite and impaired satiety, contributing to overeating and metabolic dysfunction. Additionally, circadian disruptions further impair metabolic processes, exacerbating obesity. The present article underscores the importance of understanding the molecular interplay between circadian rhythms and gastrointestinal peptides, particularly in the context of obesity. While some molecular interactions, such as the regulation of GLP-1 and PYY by reverberation of circadian rhythm α (REV-ERBα) and retinoic acid-related orphan receptor α (RORα), are well-established, clinical studies are scarce. Future research is expected to explore these pathways in obesity management, especially with the rise of incretin-based treatments like semaglutide. A deeper understanding of hypothalamic molecular mechanisms could lead to novel pharmacological and non-pharmacological therapies for obesity.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"185 ","pages":"Article 171356"},"PeriodicalIF":2.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391331","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":"Peptide‑based therapeutic strategies for glioma: Current state and prospects","authors":"Yajing Mi ,&nbsp;Pengtao Jiang ,&nbsp;Jing Luan ,&nbsp;Lin Feng ,&nbsp;Dian Zhang ,&nbsp;Xingchun Gao","doi":"10.1016/j.peptides.2025.171354","DOIUrl":"10.1016/j.peptides.2025.171354","url":null,"abstract":"<div><div>Glioma is a prevalent form of primary malignant central nervous system tumor, characterized by its cellular invasiveness, rapid growth, and the presence of the blood-brain barrier (BBB)/blood-brain tumor barrier (BBTB). Current therapeutic approaches, such as chemotherapy and radiotherapy, have shown limited efficacy in achieving significant antitumor effects. Therefore, there is an urgent demand for new treatments. Therapeutic peptides represent an innovative class of pharmaceutical agents with lower immunogenicity and toxicity. They are easily modifiable via chemical means and possess deep tissue penetration capabilities which reduce side effects and drug resistance. These unique pharmacokinetic characteristics make peptides a rapidly growing class of new therapeutics that have demonstrated significant progress in glioma treatment. This review outlines the efforts and accomplishments in peptide-based therapeutic strategies for glioma. These therapeutic peptides can be classified into four types based on their anti-tumor function: tumor-homing peptides, inhibitor/antagonist peptides targeting cell surface receptors, interference peptides, and peptide vaccines. Furthermore, we briefly summarize the results from clinical trials of therapeutic peptides in glioma, which shows that peptide-based therapeutic strategies exhibit great potential as multifunctional players in glioma therapy.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"185 ","pages":"Article 171354"},"PeriodicalIF":2.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372529","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":"Association among nesfatin-1, obesity category, presence of obesity-related complications, and eating patterns in patients with obesity: Results of a single endocrine centre observational study","authors":"Ewa Milewska-Kobos ,&nbsp;Ewelina Szczepanek- Parulska ,&nbsp;Martyna Marciniak ,&nbsp;Elżbieta Wrotkowska ,&nbsp;Maja Cieślewicz ,&nbsp;Agnieszka Dobrowolska ,&nbsp;Marek Ruchala","doi":"10.1016/j.peptides.2025.171355","DOIUrl":"10.1016/j.peptides.2025.171355","url":null,"abstract":"<div><div>Since its discovery, nesfatin-1 (N1) has been recognised as an anorexigenic agent potentially related to obesity pathogenesis and development, including its modulatory effect on the brain’s reward system and eating behaviours. As the results from human studies examining the relation between N1 serum levels, body mass index (BMI), and metabolic status are scarce and inconclusive, we aimed to investigate the association between serum N1 levels and obesity categories, obesity-related complications, and disturbed eating behaviour. We studied 110 patients with obesity divided into obesity categories according to their BMI and metabolic status. N1 was measured in a fasting state (N1⁰) and 2 h after a glucose load (N1²) and correlated with anthropometric measurements, serum analysis, and the presence of selected obesity-related complications. Neither N1⁰ nor N1² correlated significantly with obesity; however, N1⁰ tended to be high in patients with a high BMI. A positive correlation was observed among N1², fat-free mass (p = 0.022), and muscle mass (p = 0.02). We found positive correlations between N1⁰ and N1² with aspartate aminotransferase (p = 0.012 and p = 0.022, respectively) and alanine aminotransferase (p = 0.027 and p = 0.006, respectively). Patients with dyslipidaemia had significantly higher N1⁰ (p = 0.03) and N1² (p = 0.049) levels. Neither N1⁰ nor N1² correlated significantly with disturbed eating behaviour; however, low N1⁰ levels were associated with a hedonic eating pattern (p = 0.03). N1 may be involved in the pathogenesis of obesity and obesity-related complications; however, owing to the complex mechanisms of its secretion and action, further clinical and experimental research is needed.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"185 ","pages":"Article 171355"},"PeriodicalIF":2.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349232","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":"Ghrelin promotes chronic diabetic wound healing by regulating keratinocyte proliferation and migration through the ERK1/2 pathway","authors":"Yukang Zhang ,&nbsp;Yuan Chen ,&nbsp;Kailin Li ,&nbsp;Cong Chen ,&nbsp;Yong Hu ,&nbsp;Xian Li","doi":"10.1016/j.peptides.2025.171350","DOIUrl":"10.1016/j.peptides.2025.171350","url":null,"abstract":"<div><div>Delayed wound healing is a complication of diabetes mellitus and can lead to infection, sepsis, and amputation. Despite the currently available treatments, the global burden of diabetes-related wounds is growing; thus, more effective therapy for diabetic wounds is urgently needed. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is a 28-amino acid peptide hormone. Some reports have confirmed the therapeutic effects of ghrelin on diabetes mellitus and its complications. However, the effects and corresponding mechanisms of ghrelin on chronic diabetic wounds remain unknown. In this study, we explored the effect of ghrelin on diabetic wound healing and investigated the associated mechanisms. We showed that ghrelin accelerated wound healing in diabetic rats by promoting the proliferation and migration of keratinocytes. Re-epithelialization was accelerated in ghrelin-treated wounds, thicker and longer newly formed epidermis and more dividing keratinocytes were observed. We further confirmed that ghrelin regulated keratinocytes by activating the ERK1/2 pathway through its receptor growth hormone secretagogue receptor 1a (GHSR1a). Ghrelin also significantly reduced the levels of pro-inflammatory cytokines and increased the deposition of collagen in diabetic wounds. Our data provides preclinical evidence for the potential application of ghrelin as a compound to promote diabetic wound healing and clarifies the molecular mechanism.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"184 ","pages":"Article 171350"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009321","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":"Effects of irisin on ovariectomy-induced depression, anxiety, and bodyweight growth in female mice","authors":"Xupei Xie ,&nbsp;Yanling Zhang ,&nbsp;Jianping He","doi":"10.1016/j.peptides.2025.171349","DOIUrl":"10.1016/j.peptides.2025.171349","url":null,"abstract":"<div><div>Hormone replacement therapy (HRT) for postmenopausal syndrome (PMS) carries high risks of undesirable side effects. This study explores irisin as a potential alternative to HRT and investigates the underlying mechanisms. Ovariectomized (OVX) female mice was used as an animal model. The experimental mice were divided into sham, OVX, OVX + irisin (1, 3 μg/kg), OVX+ estradiol (0.5 mg/kg), and OVX + irisin + compound C (AMPK inhibitor) groups. Results showed that OVX induced depression, anxiety, and bodyweight growth in female mice. These OVX-induced abnormalities were reversed by irisin treatment, while AMPK inhibitor abolished irisin’s function, indicating that irisin’s therapeutic effects on OVX mice were achieved by activating AMPK. Moreover, irisin could increase pAMPK levels and ameliorate the overexpression of NF-κB and its downstream factors including inflammatory factors (IL-1β, IL-6, and TNF-α) and neurotoxic mediators (COX-2 and iNOS) in the hippocampus, frontal cortex, and serum of the OVX mice. However, irisin did not affect hypothalamus pAMPK level or food intake. These findings indicate that irisin’s therapeutic effects on depression and anxiety may be linked to its inhibition of inflammatory factors and neurotoxic mediators in the serum and brain, occurring through the AMPK/NF-κB pathway. Additionally, irisin’s effect of reducing bodyweight may be associated with an increase in serum pAMPK level, rather than a direct impact on food intake. Further mechanistic exploration revealed that the beneficial effects of irisin, including both the attenuation of bodyweight gain and the improvement of neurological deficits, are attributed to the activation of αVβ5 receptors.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"184 ","pages":"Article 171349"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009442","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}