Peptides最新文献_第7页

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities 多功能肠促胰岛素肽在治疗2型糖尿病、肥胖及相关合并症中的应用

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-05-01 Epub Date: 2025-03-11 DOI: 10.1016/j.peptides.2025.171380

Clifford J. Bailey , Peter R. Flatt , J. Michael Conlon

Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and ‘real-world’ studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).

最近关于以肽为基础的肠促胰岛素治疗的研究主要集中在胰高血糖素样肽-1 （GLP-1）受体激动剂semaglutide和双重激动剂tizepatide，它们结合GLP-1和葡萄糖依赖性胰岛素性多肽（GIP）受体。随机临床试验和“现实世界”研究已经证实，这些药物在不同人群中具有显著的降糖和减肥功效。这些人包括不同的种族群体、有或没有糖尿病和/或超重或肥胖的年轻人和老年人。最近的研究还证实，除了改善血糖和体重控制所带来的好处外，还可以预防心血管和肾脏疾病的发生和发展。新出现的证据表明，肠促胰岛素疗法可以额外改善脂肪肝疾病、慢性炎症、睡眠呼吸暂停以及可能的退行性骨疾病和认知能力下降。正在开发的新的基于肠促胰岛素的肽疗法包括长效胰高血糖素受体激动剂（LY3324954），双GLP-1/胰高血糖素受体激动剂（survodutide, pemvidutide, mazdutide, G49），三重GLP-1/GIP/胰高血糖素受体激动剂（利特鲁肽，依福西肽类），半马鲁肽与胰高血糖素类似物cagrilintide的组合（CagriSema），单分子GLP-1/胰高血糖素受体双激动剂（amycretin），以及具有GLP-1受体激动剂的GIP受体抗体（MariTide）。基于多靶点肠促胰岛素的合成肽的创造为改善2型糖尿病和肥胖的管理提供了机会，并为扩大相关合并症提供了新的治疗方法。回顾的目的是让读者熟悉2023年到现在（2025年2月）该领域的发展。

{"title":"Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities","authors":"Clifford J. Bailey , Peter R. Flatt , J. Michael Conlon","doi":"10.1016/j.peptides.2025.171380","DOIUrl":"10.1016/j.peptides.2025.171380","url":null,"abstract":"<div><div>Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and ‘real-world’ studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171380"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601618","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}

引用次数: 0

KLF4 regulates FAM3A to promotes angiotensin II-induced proliferation and migration of vascular smooth muscle cells through the PI3K/AKT signaling pathway KLF4通过PI3K/AKT信号通路调控FAM3A，促进血管紧张素ii诱导的血管平滑肌细胞增殖和迁移。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-05-01 Epub Date: 2025-02-25 DOI: 10.1016/j.peptides.2025.171379

Min Zhang, Rong Lei, Liqiong Wang, Yimin Jiang, Xiaoyan Zhou, Yuquan Wang

Background

Hypertension, a major cause of cardiovascular disease, is linked to vascular remodeling, which is influenced by phenotypic changes in vascular smooth muscle cells (VSMCs). Studies have shown that KLF4 influences vascular remodeling by promoting VSMC dedifferentiation, increasing proliferation, and enhancing inflammatory responses, while FAM3 may play a key role in VSMC migration and proliferation. Angiotensin II (Ang II) contributes to remodeling, but the mechanisms are unclear.

Methods

Ang II was used to stimulate VSMCs in order to evaluate the expression levels of KLF4 and FAM3A. EdU assays, transwell and scratch wound healing assays measured proliferation and migration. KLF4 knockdown and overexpression experiments were performed to examine the effects on FAM3A expression and VSMC behavior. Western blotting was conducted to analyze protein expression levels of KLF4, FAM3A, and PI3K/AKT signaling components. Bioinformatics analysis was used to predict KLF4 binding sites on the FAM3A promoter. Luciferase and CHIP assays confirmed regulation.

Results

Ang II stimulation increased VSMC proliferation, migration, and the expression of KLF4 and FAM3A. Knockdown of KLF4 reduced Ang II-induced proliferation and migration of VSMCs, accompanied by decreased FAM3A expression. Conversely, overexpression of KLF4 enhanced FAM3A levels, promoting VSMC proliferation and migration. Bioinformatics, luciferase reporter assays and CHIP assay confirmed that KLF4 directly binds to the FAM3A promoter. FAM3A knockdown inhibited Ang II-induced VSMC proliferation and migration by reducing PI3K/AKT pathway activation, whereas FAM3A overexpression reversed the inhibitory effects of KLF4 knockdown.

Conclusion

KLF4 transcriptionally regulates FAM3A, modulating Ang II-induced VSMC proliferation and migration through the PI3K/AKT signaling pathway.

背景：高血压是心血管疾病的主要原因之一，与血管重构有关，血管重构受血管平滑肌细胞（VSMCs）表型变化的影响。研究表明KLF4通过促进VSMC去分化、增加增殖、增强炎症反应等方式影响血管重构，而FAM3可能在VSMC迁移和增殖中发挥关键作用。血管紧张素II （Ang II）有助于重塑，但机制尚不清楚。方法：采用Angⅱ刺激VSMCs，评价KLF4和FAM3A的表达水平。EdU试验、transwell和划伤愈合试验测量了增殖和迁移。通过KLF4敲低和过表达实验，观察对FAM3A表达和VSMC行为的影响。Western blotting分析KLF4、FAM3A、PI3K/AKT信号组分的蛋白表达水平。利用生物信息学分析预测FAM3A启动子上KLF4的结合位点。荧光素酶和CHIP检测证实有调节作用。结果：Ang II刺激增加VSMC的增殖、迁移和KLF4、FAM3A的表达。敲低KLF4可降低Angⅱ诱导的VSMCs的增殖和迁移，同时降低FAM3A的表达。相反，过表达KLF4可增强FAM3A水平，促进VSMC的增殖和迁移。生物信息学、荧光素酶报告基因检测和CHIP检测证实KLF4直接结合FAM3A启动子。FAM3A敲低通过降低PI3K/AKT通路激活抑制Ang ii诱导的VSMC增殖和迁移，而FAM3A过表达逆转了KLF4敲低的抑制作用。结论：KLF4转录调控FAM3A，通过PI3K/AKT信号通路调节Ang ii诱导的VSMC增殖和迁移。

{"title":"KLF4 regulates FAM3A to promotes angiotensin II-induced proliferation and migration of vascular smooth muscle cells through the PI3K/AKT signaling pathway","authors":"Min Zhang, Rong Lei, Liqiong Wang, Yimin Jiang, Xiaoyan Zhou, Yuquan Wang","doi":"10.1016/j.peptides.2025.171379","DOIUrl":"10.1016/j.peptides.2025.171379","url":null,"abstract":"<div><h3>Background</h3><div>Hypertension, a major cause of cardiovascular disease, is linked to vascular remodeling, which is influenced by phenotypic changes in vascular smooth muscle cells (VSMCs). Studies have shown that KLF4 influences vascular remodeling by promoting VSMC dedifferentiation, increasing proliferation, and enhancing inflammatory responses, while FAM3 may play a key role in VSMC migration and proliferation. Angiotensin II (Ang II) contributes to remodeling, but the mechanisms are unclear.</div></div><div><h3>Methods</h3><div>Ang II was used to stimulate VSMCs in order to evaluate the expression levels of KLF4 and FAM3A. EdU assays, transwell and scratch wound healing assays measured proliferation and migration. KLF4 knockdown and overexpression experiments were performed to examine the effects on FAM3A expression and VSMC behavior. Western blotting was conducted to analyze protein expression levels of KLF4, FAM3A, and PI3K/AKT signaling components. Bioinformatics analysis was used to predict KLF4 binding sites on the FAM3A promoter. Luciferase and CHIP assays confirmed regulation.</div></div><div><h3>Results</h3><div>Ang II stimulation increased VSMC proliferation, migration, and the expression of KLF4 and FAM3A. Knockdown of KLF4 reduced Ang II-induced proliferation and migration of VSMCs, accompanied by decreased FAM3A expression. Conversely, overexpression of KLF4 enhanced FAM3A levels, promoting VSMC proliferation and migration. Bioinformatics, luciferase reporter assays and CHIP assay confirmed that KLF4 directly binds to the FAM3A promoter. FAM3A knockdown inhibited Ang II-induced VSMC proliferation and migration by reducing PI3K/AKT pathway activation, whereas FAM3A overexpression reversed the inhibitory effects of KLF4 knockdown.</div></div><div><h3>Conclusion</h3><div>KLF4 transcriptionally regulates FAM3A, modulating Ang II-induced VSMC proliferation and migration through the PI3K/AKT signaling pathway.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171379"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524094","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}

引用次数: 0

Adropin: A cardio-metabolic hormone in the periphery, a neurohormone in the brain? 促肾上腺素：外周的心脏代谢激素，大脑中的神经激素？

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-05-01 Epub Date: 2025-03-15 DOI: 10.1016/j.peptides.2025.171391

Andrew A. Butler , Peter J. Havel

Whole-body metabolic homeostasis is regulated by physiological responses across organs and tissues to proteins and peptides (<50 amino acids) released into the interstitial and circulatory spaces. These secreted factors integrate signals of metabolic status at both the cellular and systemic level, regulate the intake and distribution of ingested and stored energy substrates across tissues, and minimize toxicity from excessive excursions in circulating concentrations of energy substrates (for example, glucotoxicity and lipotoxicity). The proteins and peptides that are known to be secreted into circulation that are involved in regulating metabolic processes represent a fraction of the secretome predicted by the Human Proteome Atlas. Many undiscovered leads for targeting new therapies for metabolic diseases may therefore exist. In this review, we discuss the biology of adropin, the peptide encoded by the Energy Homeostasis Associated (ENHO) gene. First described as a feeding-responsive, liver-secreted peptide (“hepatokine”) involved in metabolic homeostasis, > 2 decades of research indicate adropin is a stress-responsive peptide acting across multiple tissues, vascular, and organ systems. Adropin modulates the responses of liver and muscle to insulin and glucagon in regulating glucose homeostasis. Adropin inhibits hepatic glucose production and stimulates glycolysis but also inhibits tissue fibrosis and maintains vascular health in aging and metabolic disease states. Adropin is also highly expressed in the central nervous system where recent data suggest neuroprotective actions. Collectively, these results suggest the potential for targeting adropin in reducing risk of both metabolic (metabolic syndrome/type-2 diabetes) and neurodegenerative diseases in the context of aging and obesity.

全身代谢稳态是通过器官和组织对蛋白质和肽的生理反应来调节的（20年的研究表明，adropin是一种应激反应肽，作用于多个组织、血管和器官系统）。Adropin调节肝脏和肌肉对胰岛素和胰高血糖素的反应，调节葡萄糖稳态。Adropin抑制肝脏葡萄糖生成并刺激糖酵解，但也抑制组织纤维化并在衰老和代谢性疾病状态下维持血管健康。Adropin在中枢神经系统中也高度表达，最近的数据表明它具有神经保护作用。总的来说，这些结果表明，在衰老和肥胖的背景下，靶向adropin在降低代谢（代谢综合征/ 2型糖尿病）和神经退行性疾病的风险方面具有潜力。

{"title":"Adropin: A cardio-metabolic hormone in the periphery, a neurohormone in the brain?","authors":"Andrew A. Butler , Peter J. Havel","doi":"10.1016/j.peptides.2025.171391","DOIUrl":"10.1016/j.peptides.2025.171391","url":null,"abstract":"<div><div>Whole-body metabolic homeostasis is regulated by physiological responses across organs and tissues to proteins and peptides (<50 amino acids) released into the interstitial and circulatory spaces. These secreted factors integrate signals of metabolic status at both the cellular and systemic level, regulate the intake and distribution of ingested and stored energy substrates across tissues, and minimize toxicity from excessive excursions in circulating concentrations of energy substrates (for example, glucotoxicity and lipotoxicity). The proteins and peptides that are known to be secreted into circulation that are involved in regulating metabolic processes represent a fraction of the secretome predicted by the Human Proteome Atlas. Many undiscovered leads for targeting new therapies for metabolic diseases may therefore exist. In this review, we discuss the biology of adropin, the peptide encoded by the Energy Homeostasis Associated (<em>ENHO</em>) gene<em>.</em> First described as a feeding-responsive, liver-secreted peptide (“hepatokine”) involved in metabolic homeostasis, > 2 decades of research indicate adropin is a stress-responsive peptide acting across multiple tissues, vascular, and organ systems. Adropin modulates the responses of liver and muscle to insulin and glucagon in regulating glucose homeostasis. Adropin inhibits hepatic glucose production and stimulates glycolysis but also inhibits tissue fibrosis and maintains vascular health in aging and metabolic disease states. Adropin is also highly expressed in the central nervous system where recent data suggest neuroprotective actions. Collectively, these results suggest the potential for targeting adropin in reducing risk of both metabolic (metabolic syndrome/type-2 diabetes) and neurodegenerative diseases in the context of aging and obesity.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171391"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649891","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}

引用次数: 0

Corrigendum to “Oxytocin attenuates cardiac hypertrophy by improving cardiac glucose metabolism and regulating OXTR/JAK2/STAT3 axis” [Peptides 182 (2024) 171323] “催产素通过改善心脏糖代谢和调节OXTR/JAK2/STAT3轴来减轻心脏肥厚”的更正[Peptides 182(2024) 171323]。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-05-01 Epub Date: 2025-03-08 DOI: 10.1016/j.peptides.2025.171365

Yuqiao Yang , Jin Liu , Lingyan Wang , Wen Wu, Quan Wang, Yu Zhao, Xi Qian, Zhuoran Wang, Na Fu, Yanqiong Wang, Jinqiao Qian

引用次数: 0

A murine model of obesity with hyperinsulinemia and hepatic steatosis involving neurosecretory protein GL gene and a low-fat/medium-sucrose diet 高胰岛素血症和肝脂肪变性的小鼠模型，涉及神经分泌蛋白GL基因和低脂/中糖饮食。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-04-01 Epub Date: 2025-02-23 DOI: 10.1016/j.peptides.2025.171376

Yuki Narimatsu , Masaki Kato , Eiko Iwakoshi-Ukena, Megumi Furumitsu, Kazuyoshi Ukena

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). Npgl overexpression promoted fat accumulation in the white adipose tissues in 2 weeks. Basal insulin levels were increased and pancreatic islets expanded following Npgl overexpression. Histological and molecular biological approaches revealed that Npgl overexpression enhanced de novo lipogenesis, leading to hepatic steatosis. Nine-week overexpression of Npgl exacerbated obesity and hyperinsulinemia, resulting in hyperglycemia. Moreover, prolonged Npgl overexpression aggravated fat accumulation in the liver with a change in the lipid metabolic pathway. These findings suggest that Npgl overexpression readily leads to obesity with hyperinsulinemia and hepatic steatosis in ICR mice under an LFMSD.

以肝脏脂肪变性和胰岛素失调为特征的代谢功能障碍相关脂肪变性肝病（MASLD）正在成为慢性肝脏疾病的常见原因。虽然内分泌干扰在MASLD的发生和发展中被认为是至关重要的，但反映高胰岛素血症和肝脂肪变性的有效动物模型有限。在这里，我们提出了一个结合神经肽效应和膳食营养的MASLD小鼠模型。我们采用低脂/中糖饮食（LFMSD）下ICR小鼠下丘脑中编码神经分泌蛋白GL （NPGL）的基因的慢性过表达。Npgl过表达促进白色脂肪组织在2周内的脂肪积累。Npgl过表达后，基础胰岛素水平升高，胰岛扩大。组织学和分子生物学方法显示，Npgl过表达增强了肝脏脂肪生成，导致肝脏脂肪变性。9周后，Npgl的过度表达加重了肥胖和高胰岛素血症，导致高血糖。此外，Npgl过表达的延长通过改变脂质代谢途径加剧了肝脏中的脂肪积累。这些发现表明，Npgl过表达容易导致LFMSD下的ICR小鼠肥胖并伴有高胰岛素血症和肝脏脂肪变性。

{"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 , Masaki Kato , Eiko Iwakoshi-Ukena, Megumi Furumitsu, 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":"2025-04-01","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}

引用次数: 0

Cholecystokinin - portrayal of an unfolding peptide messenger system 胆囊收缩素-展开肽信使系统的写照

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1016/j.peptides.2025.171369

Jens F. Rehfeld

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 in vitro 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.

这篇综述描述了在2025年应该如何理解经典的肠道激素——胆囊收缩素（CCK）。在研究胃肠激素的早期生理学传统中，激素是以导致它们被发现的功能来命名的。因此，在1928年，调节胆囊收缩的上肠激素因子被称为胆囊收缩素。1968年，Viktor Mutt和Erik Jorpes发现该因子的猪结构是由33个氨基酸残基（CCK-33）组成的o -硫酸化和羧化肽。其c端生物活性七肽酰胺被证明是与胃窦激素胃泌素同源的。该结构允许体外合成肽片段用于生理研究和生产cck抗体用于免疫测定和免疫组织化学。今天，这些工具揭示了CCK是高度复杂的：CCK是一种异质的多功能肽信使系统，在肠道内外广泛表达。因此，CCK基因编码六种不同的生物活性肽（CCK-83、- 58、- 33、- 22、-8和- 5），这些肽以细胞特异性的方式以o -硫酸盐和非硫酸盐形式表达。此外，CCK肽不仅仅是激素。它们也是有效的神经递质、旁分泌生长和饱足因子、抗炎细胞因子、肠促胰岛素、潜在的生育因子和有用的肿瘤标志物。此外，CCK具有近6亿年的系统发育历史。由于CCK是大脑中主要的肽递质，其表达量超过任何其他神经肽，因此对CCK的神经科学特别感兴趣。反之亦然，哺乳动物的大脑是CCK的主要产生部位。

{"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":"2025-04-01","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}

引用次数: 0

Erythropoietin improves spatial and nonspatial memory defects by suppressing oxidative damage, inflammation and apoptosis against ethanol neurotoxicity in the developing male rat hippocampus 促红细胞生成素通过抑制乙醇神经毒性对雄性大鼠海马的氧化损伤、炎症和凋亡，改善空间和非空间记忆缺陷

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1016/j.peptides.2025.171368

Raheleh Rafaiee , Fahimeh Mohseni , Mehdi khaksari , Behzad Garmabi , Alireza Masoudi , Zhaleh Jamali , Shima Mohammadi , Alieh Bashghareh

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 < 0.001). EPO dramatically decreased the amount of caspase 3 positive cells in the CA1 area of the hippocampus (P < 0.01). EPO increased total superoxide dismutase activity (P < 0.05), glutathione concentrations (P < 0.05) and catalase levels (P < 0.001). EPO also attenuated the production of TNF-α and malondialdehyde (P < 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.

产前过量接触乙醇会导致胎儿酒精谱系障碍（FASD）。酒精的神经毒性导致动物海马在这段时间内发生变化，导致海马相关功能受损，包括记忆/学习和认知。肝脏和肾脏产生红细胞生成素（EPO）。未成熟神经元合成EPO在胚胎期也起着决定性作用。此外，在病理生理条件下，外源性EPO在发育中的大脑中发挥其神经认知作用。本研究的目的是研究EPO在乙醇诱导神经发育毒性增加后的保护作用。从出生后2-10天开始，雄性Wistar大鼠幼崽插管5/27 g/kg/天的乙醇剂量，类似于人类妊娠的最后三个月。随后立即注射EPO （1000 /2000 U/kg, s.c）。用Morris水迷宫测试空间记忆（第36-40天），用新物体任务测试非空间识别记忆（第39-40天）。测定抗氧化酶、TNF-α (ELISA)和caspase-3（免疫组化染色）浓度。目前的研究表明，EPO可显著减轻空间和非空间记忆障碍（P <； 0.001）。EPO显著降低海马CA1区caspase 3阳性细胞的数量（P <； 0.01）。EPO增加了总超氧化物歧化酶活性（P <； 0.05）、谷胱甘肽浓度（P <； 0.05）和过氧化氢酶水平（P <； 0.001）。EPO还能减弱TNF-α和丙二醛的产生（P <； 0.05）。考虑到EPO对乙醇诱导的神经毒性增加的保护作用，它是FASD的一种可行的治疗选择，尽管还需要更多的研究。

{"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 , Fahimeh Mohseni , Mehdi khaksari , Behzad Garmabi , Alireza Masoudi , Zhaleh Jamali , Shima Mohammadi , 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 < 0.001). EPO dramatically decreased the amount of caspase 3 positive cells in the CA1 area of the hippocampus (P < 0.01). EPO increased total superoxide dismutase activity (P < 0.05), glutathione concentrations (P < 0.05) and catalase levels (P < 0.001). EPO also attenuated the production of TNF-α and malondialdehyde (P < 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":"2025-04-01","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}

引用次数: 0

The role of leptin and ghrelin in the regulation of appetite in obesity 瘦素和胃饥饿素在肥胖患者食欲调节中的作用

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1016/j.peptides.2025.171367

Kinga Skoracka , Szymon Hryhorowicz , Piotr Schulz , Agnieszka Zawada , Alicja Ewa Ratajczak-Pawłowska , Anna Maria Rychter , Ryszard Słomski , Agnieszka Dobrowolska , Iwona Krela-Kaźmierczak

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.

瘦素和胃饥饿素是两种关键的激素，在调节食欲和能量平衡方面发挥相反的作用。胃饥饿素在与受体结合后刺激食欲和食物摄入，并随后激活弓状核中的供氧神经元。相反，瘦素已被证明可以抑制食欲，减少食物摄入。这是通过抑制胃饥饿素激活的神经元而发生的，同时激活那些促进饱腹感和增加能量消耗的神经元。尽管瘦素水平升高，但缺乏生物反应，这被称为瘦素抵抗，在体重过重的个体中观察到，这是一个重大挑战。由于胃饥饿素和瘦素信号的失调与肥胖和其他代谢紊乱的发展有关，深入了解影响这两种激素的遗传决定因素可能有助于更全面地掌握支撑肥胖发病机制的复杂相互作用。

{"title":"The role of leptin and ghrelin in the regulation of appetite in obesity","authors":"Kinga Skoracka , Szymon Hryhorowicz , Piotr Schulz , Agnieszka Zawada , Alicja Ewa Ratajczak-Pawłowska , Anna Maria Rychter , Ryszard Słomski , Agnieszka Dobrowolska , 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":"2025-04-01","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}

引用次数: 0

Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice 杜拉鲁肽通过抑制糖尿病小鼠nrf2依赖性铁下垂加速糖尿病伤口愈合。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-03-01 Epub Date: 2025-02-13 DOI: 10.1016/j.peptides.2025.171366

Liuqing Xi , Juan Du , Yan Lu , Wen Xue , Yuxuan Xia , Tingxu Chen , Yang Xiao , Nuo Xu , Yansheng Wang , Jianfang Gao , Wenyi Li , Shan Huang

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 db/db diabetic mice. Subsequently, dulaglutide was delivered via subcutaneous injections surrounding the wound’s perimeter, and the wound closure rates were monitored. In vitro, 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. In vitro, dulaglutide promoted HaCaT cell proliferation and migration under HG conditions. Exposure of HaCaT cells to HG resulted in ferroptosis in vivo and in vitro, 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.

胰高血糖素样肽-1受体激动剂（GLP-1RAs）常用于治疗2型糖尿病（T2DM）。几种GLP-1RAs （Exendin-4和利拉鲁肽）已被证明可以加速糖尿病伤口愈合。本研究的主要目的是探讨杜拉鲁肽在糖尿病小鼠伤口愈合中的作用，并确定其潜在的机制。在db/db糖尿病小鼠背部制造圆形全层伤口。随后，在伤口周围皮下注射杜拉鲁肽，并监测伤口愈合率。体外，在高糖（HG）条件下用杜拉鲁肽处理角质形成细胞，并通过细胞计数试剂盒-8 （CCK-8）和EdU检测评估细胞活力。通过测定铁2+水平和氧化应激水平以及铁下垂标志物的表达来评估杜拉鲁肽在铁下垂中的作用。结果表明，杜拉鲁肽处理可增加血管内皮生长因子（VEGF）和增殖标志物Ki67的表达，从而促进糖尿病小鼠伤口愈合。在体外，dulaglutide促进HG条件下HaCaT细胞的增殖和迁移。HaCaT细胞暴露于HG后，体内和体外均出现铁下垂，铁下垂表现为Fe2+、活性氧（ROS）和丙二醛（MDA）水平显著升高，谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平降低。所有这些作用都被杜拉鲁肽逆转了。在机制上，dulaglutide激活了HG条件下nfe2相关因子2 （Nrf2）信号，从而增加谷胱甘肽过氧化物酶（Gpx4）和溶质载体家族7-成员11 （Slc7a11）的表达，从而抑制铁凋亡。总之，这些结果表明杜拉鲁肽通过调节nrf2依赖性铁下垂来治疗糖尿病伤口是一种很有前景的药物。

{"title":"Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice","authors":"Liuqing Xi , Juan Du , Yan Lu , Wen Xue , Yuxuan Xia , Tingxu Chen , Yang Xiao , Nuo Xu , Yansheng Wang , Jianfang Gao , Wenyi Li , 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<sup>2 +</sup> 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 Fe<sup>2+</sup>, 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":"2025-03-01","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}

引用次数: 0

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 肥胖患者的nesfatin-1、肥胖类别、肥胖相关并发症和饮食模式之间的关系：一项内分泌中心观察性研究的结果

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-03-01 Epub Date: 2025-02-05 DOI: 10.1016/j.peptides.2025.171355

Ewa Milewska-Kobos , Ewelina Szczepanek- Parulska , Martyna Marciniak , Elżbieta Wrotkowska , Maja Cieślewicz , Agnieszka Dobrowolska , Marek Ruchala

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.

自发现以来，nesfatin-1 （N1）已被认为是一种厌食因子，可能与肥胖的发病和发展有关，包括其对大脑奖励系统和饮食行为的调节作用。由于人类研究N1血清水平、体重指数（BMI）和代谢状态之间关系的结果很少且不确定，因此我们旨在调查血清N1水平与肥胖类别、肥胖相关并发症和饮食行为紊乱之间的关系。我们研究了110例肥胖患者，根据BMI和代谢状况将其分为肥胖类别。N1在空腹状态（N10）和葡萄糖负荷后2 h （N12）测量，并与人体测量、血清分析和选择的肥胖相关并发症的存在相关。N10和N12与肥胖均无显著相关性；然而，N10在BMI高的患者中往往较高。N12、无脂质量（p = 0.022）和肌肉质量（p = 0.02）呈正相关。我们发现N10和N12与天冬氨酸转氨酶（p = 0.012和p = 0.022）和丙氨酸转氨酶（p = 0.027和p = 0.006）呈正相关。血脂异常患者N10 （p = 0.03）和N12 （p = 0.049）水平显著升高。N10和N12与饮食行为紊乱均不显著相关；然而，低N10水平与享乐饮食模式相关（p = 0.03）。N1可能参与肥胖及肥胖相关并发症的发病机制；但由于其分泌和作用机制复杂，需要进一步的临床和实验研究。

{"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 , Ewelina Szczepanek- Parulska , Martyna Marciniak , Elżbieta Wrotkowska , Maja Cieślewicz , Agnieszka Dobrowolska , 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 (N1<sup>0</sup>) and 2 h after a glucose load (N1<sup>2</sup>) and correlated with anthropometric measurements, serum analysis, and the presence of selected obesity-related complications. Neither N1<sup>0</sup> nor N1<sup>2</sup> correlated significantly with obesity; however, N1<sup>0</sup> tended to be high in patients with a high BMI. A positive correlation was observed among N1<sup>2</sup>, fat-free mass (p = 0.022), and muscle mass (p = 0.02). We found positive correlations between N1<sup>0</sup> and N1<sup>2</sup> 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 N1<sup>0</sup> (p = 0.03) and N1<sup>2</sup> (p = 0.049) levels. Neither N1<sup>0</sup> nor N1<sup>2</sup> correlated significantly with disturbed eating behaviour; however, low N1<sup>0</sup> 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":"2025-03-01","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}

引用次数: 0