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更新于：2025-05-07

LEAP2

更新于：2025-05-07

基本信息

别名

LEAP-2、LEAP2、liver enriched antimicrobial peptide 2

+ [1]

简介

Has an antimicrobial activity.

关联

靶点

GHSR x LEAP2

作用机制

GHSR拮抗剂 [+1]

在研机构

University of Copenhagen

原研机构

University of Copenhagen

在研适应症

2型糖尿病

非在研适应症

肥胖

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

Liver-expressed antimicrobial peptide 2

靶点

LEAP2

作用机制

LEAP2 modulators

在研机构-

原研机构

IPF PharmaCeuticals GmbH

在研适应症-

非在研适应症

细菌感染

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 LEAP2 相关的临床试验

NCT06845033

/ Not yet recruitingN/AIIT

Effects of Antagonizing the Ghrelin Receptor on Brain Food Cue Reactivity in Obesity

The naturally occurring peptide hormone liver-expressed antimicrobial peptide 2 (LEAP2) in an antagonist/inverse agonist towards the ghrelin receptor. Ghrelin administration has previously been shown to increase food cue reactivity in brain regions related to appetite and reward using functional MRI scans.
The aim of this clinical study is to investigate the effects of LEAP2 infusion on food cue reactivity in brain regions related to appetite and reward. Since LEAP2 is an antagonist/inverse agonist towards the ghrelin receptor we hypothesize, that LEAP2 infusion will decrease food cue reactivity in the above-mentioned regions compared to placebo infusion.
Participants with obesity (BMI 30-50 kg/m2) will be included and complete two experimental days with either LEAP2 or placebo infusion in a randomized crossover manner. On experimental days, participants will undergo a MRI scan with functional and anatomical modalities.
The study will attribute to gain a deeper understanding of the ghrelin system and its interaction with appetite regulation.

开始日期2025-05-01

申办/合作机构-

NCT05603598

/ Unknown statusN/AIIT

LEAP2 on Postprandial Glucose Metabolism and Food Intake in Obese Males

The study aims to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in obese volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in obese subjects.

开始日期2022-08-24

申办/合作机构-

NCT04897984

/ Completed早期临床1期IIT

The Kinetics of LEAP2 in Man

The study aims to investigate the kinetics of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) in healthy volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in healthy subjects.

开始日期2021-05-24

申办/合作机构

Gentofte Hospital

100 项与 LEAP2 相关的临床结果

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100 项与 LEAP2 相关的转化医学

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0 项与 LEAP2 相关的专利（医药）

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231

项与 LEAP2 相关的文献（医药）

2025-06-01·Journal of Affective Disorders

Associations between major depressive disorders and Parkinson's Disease and impact of their comorbidity sequence

Article

作者: Zhou, Xiaoxia ; Xu, Ruiling ; Li, Zhihong ; Xiang, Linghui ; Ren, Xiaolei ; Wu, Irene X Y

BACKGROUNDThe comorbidity of major depressive disorder (MDD) and Parkinson's disease (PD) were prevalent and has a profound impact on patients. However, whether this comorbidity results from specific pathological processes or a mutual cause-and-effect relationship was largely controversial. Additionally, although MDD can appear before or after PD, the health impact of the comorbidity sequence is poorly understood.METHODSWe used mendelian randomization (MR) and UK biobank (UKB) cohort to explore the associations between MDD and PD. MR was also utilized to investigate potential confounders. By classifying UKB patients into MDD first and PD first groups, we evaluated the health impact of the comorbidity sequence using Cox regression.RESULTSBidirectional MR and cohort study showed conflicting results. MR did not find associations between MDD followed by PD (odds ratio [OR] = 1.28, 95 % confidence interval [CI] = 0.85-1.94) or PD followed by MDD (OR = 0.99, 95 % CI = 0.97-1.01). However, the cohort study found a significant effect of MDD on PD (hazard ratio [HR] = 1.75, 95 % CI = 1.55-1.97) and PD on MDD (HR = 4.35, 95 % CI = 3.65-5.19). By performing MR on 4709 proteins, we identified ESD, LEAP2, NDRG3, NRXN3, and PLXNB2 as potential common causes of MDD and PD. Additionally, PD first group had higher risks of all-cause mortality (HR = 1.65, 95 % CI = 1.03-1.90), dementia (HR = 1.88, 95 % CI = 1.16-3.04), and aspiration pneumonia (HR = 1.89, 95 % CI = 1.09-3.27).CONCLUSIONSOur study suggested the comorbidity of MDD and PD is likely the result of certain pathological processes. Additionally, patients with PD first had higher risks of several adverse outcomes.

2025-05-01·International Journal of Biological Macromolecules

Molecular characterization of an antimicrobial peptide LEAP-2 in Onychostoma macrolepis: Expression pattern, antimicrobial ability and immunomodulation function

Article

作者: Xu, Hongzhou ; Sun, Xiaonan ; Liu, Haixia ; Jin, Yuanjiang ; Yan, Chenyang ; Xiao, Jiadong ; Li, Huanjie ; Pan, Kuiquan

Antimicrobial peptides (AMPs) as the host's antimicrobial source are promising candidates for the development of novel antibacterial agents. Our study identified and analyzed the LEAP-2 gene from the cavefish - Onychostoma macrolepis (OmLEAP-2), and antimicrobial activity of OmLEAP-2 was assessed through both in vivo and in vitro experiments. The OmLEAP-2 encodes 92 amino acids with a hydrophobic surface (LAMMPWY) and two disulfide bonds. Following A. hydrophila infection, OmLEAP-2 expression was up-regulated in the liver, spleen and intestine in Onychostoma macrolepis. Recombinant OmLEAP-2 protein exhibited dose-dependent antimicrobial activity against both Gram-negative and Gram-positive bacteria, particularly A. hydrophila and A. veronii. OmLEAP-2 overexpression not only reduced bacterial load and increased survival rate, but also suppressed expression of TNF-α and IL-1β in A. hydrophila-infected Onychostoma macrolepis. Furthermore, OmLEAP-2 regulated iron metabolism by increasing liver iron levels, altering serum iron content, and modulating iron-related genes (fpn1 and hepcidin) expression. Collectively, these findings demonstrate that OmLEAP-2 exhibits broad-spectrum antibacterial activity against aquatic pathogens and shows potential as a therapeutic peptide for treating bacterial disease.

2025-04-01·Marine Biotechnology

Impact of Probiotics on Enzyme Activities, Intestinal Microbial Remodeling, and Metabolic Pathways in American Shad (Alosa sapidissima) at High Temperatures

Article

作者: Chen, Zaizhong ; Shi, Yonghai ; Qiu, Chuwen ; Huang, Xuxiong

High temperature restricts the survival and growth of aquatic organisms. Probiotics have significant potential for mitigating the negative effects of temperature stress on fish. In this study, the American shad (Alosa sapidissima), a temperature-sensitive freshwater fish, was selected as the experimental paradigm to dissect the underlying mechanisms governing the interactions between the host and its microbiome, with a particular focus on the impact exerted by the probiotic Lactococcus lactis within a high-temperature setting. We evaluated the effects of probiotics on the growth and biochemistry of A. sapidissima by measuring relevant parameters and enzyme activities and conducted an integrated microbiome-transcriptome analysis to assess the impacts on the gut microbiota and uncover probiotic-regulated metabolic pathways. The findings of our research indicated that probiotics had beneficial effects on growth; the activities of enzymes such as LPS, T-SOD, and GSH-PX; and the gut microbial composition. Furthermore, the configuration of the intestinal microbiota underwent a transformation, as evidenced by the increased relative prevalence of bacteria with potential beneficial properties, including Bacillus, Lactococcus, and Clostridium. Liver transcriptomic analysis revealed 586 differentially expressed genes (DEGs). The expression of immune-related genes (nfil3-2, il17d, and leap2) and lipid metabolism-related genes (pla2g3 and sc5d) was strongly upregulated. KEGG enrichment analysis revealed that the DEGs were predominantly clustered within metabolic pathways such as circadian rhythm and fatty acid degradation. This study revealed that probiotics enhanced intestinal bacterial diversity and eased stress by regulating the circadian rhythm, immunity, and lipid metabolism under high-temperature conditions. This study provides a reference for the use of probiotics in A. sapidissima at high temperatures.

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