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.

Start Date24 Aug 2022

Sponsor / Collaborator-

NCT04897984 / CompletedEarly Phase 1IIT

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.

Start Date24 May 2021

Sponsor / Collaborator

Gentofte Hospital

NCT04621409 / CompletedEarly Phase 1IIT

Effects of LEAP-2 on Postprandial Glucose Metabolism and Food Intake

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

Start Date17 Nov 2020

Sponsor / Collaborator

Gentofte Hospital

100 Clinical Results associated with LEAP2

100 Translational Medicine associated with LEAP2

0 Patents (Medical) associated with LEAP2

222

Literatures (Medical) associated with LEAP2

01 Dec 2024·Molecular Biology Reports

Exploring the neuroprotective potential of KC14 peptide from Cyprinus carpio against oxidative stress-induced neurodegeneration by regulating antioxidant mechanism

Article

Author: Hussain, Shaik Althaf ; Vijayanand, Madhumitha ; Velayutham, Manikandan ; Issac, Praveen Kumar ; Shaik, Mohammed Rafi ; Guru, Ajay

BACKGROUNDOxidative stress, a condition characterized by excessive production of reactive oxygen species (ROS), can cause significant damage to cellular macromolecules, leading to neurodegeneration. This underscores the need for effective antioxidant therapies that can mitigate oxidative stress and its associated neurodegenerative effects. KC14 peptide derived from liver-expressed antimicrobial peptide-2 A (LEAP 2 A) from Cyprinus carpio L. has been identified as a potential therapeutic agent. This study focuses on the antioxidant and neuroprotective properties of the KC14 peptide is to evaluate its effectiveness against oxidative stress and neurodegeneration.METHODSThe antioxidant capabilities of KC14 were initially assessed through in silico docking studies, which predicted its potential to interact with oxidative stress-related targets. Subsequently, the peptide was tested at concentrations ranging from 5 to 45 µM in both in vitro and in vivo experiments. In vivo studies involved treating H₂O₂-induced zebrafish larvae with KC14 peptide to analyze its effects on oxidative stress and neuroprotection.RESULTSKC14 peptide showed a protective effect against the developmental malformations caused by H₂O₂ stress, restored antioxidant enzyme activity, reduced neuronal damage, and lowered lipid peroxidation and nitric oxide levels in H₂O₂-induced larvae. It enhanced acetylcholinesterase activity and significantly reduced intracellular ROS levels (p < 0.05) dose-dependently. Gene expression studies showed up-regulation of antioxidant genes with KC14 treatment under H₂O₂ stress.CONCLUSIONSThis study highlights the potent antioxidant activity of KC14 and its ability to confer neuroprotection against oxidative stress can provide a novel therapeutic agent for combating neurodegenerative diseases induced by oxidative stress.

01 Nov 2024·Environmental Toxicology

Exposure to Trimethyltin Chloride Induces Pyroptosis and Immune Dysfunction in Grass Carp CIK Cells by Activating the NF‐κB Pathway Through Oxidative Stress

Article

Author: Xu, Haotian ; Hong, Haozheng ; Xu, Shiwen ; Qi, Meng ; Ni, Xiaotong

ABSTRACTTrimethyltin chloride (TMT) is a highly toxic organotin pollutant frequently found in aquatic environments, posing a significant threat to the ecological system. The kidney plays a vital role in the body's detoxification processes, and TMT present in the environment tends to accumulate in the kidneys. However, it remained unclear whether exposure to different doses of TMT could induce pyroptosis and immune dysfunction in grass carp kidney cells (CIK cells). For this purpose, after assessing the half‐maximal inhibitory concentration (IC50) of TMT on CIK cells, we established a model for exposure of CIK cells at varying concentrations of TMT. CIK cells were treated with various doses of TMT (2.5, 5, 10 μM) for 24 h. Oxidative stress levels were measured using kits and fluorescence methods, whereas the expression of related genes was verified through western blot and quantitative real‐time PCR (qRT‐PCR). The results indicated that TMT exposure led to oxidative stress, with increased levels of ROS, H2O2, MDA, and GSH, and inhibited activities of T‐AOC, SOD, and CAT. It activated the NF‐κB pathway, leading to the upregulation of NF‐κB p65, NF‐κB p50, GSDMD, NLRP3, ASC, and Caspase‐1. Furthermore, TMT exposure also resulted in increased expression of cytokines (IL‐18, IL‐6, IL‐2, IL‐1β, and TNF‐α) and decreased expression of antimicrobial peptides (LEAP2, HEPC, and β‐defensin). In summary, exposure to TMT induces dose‐dependent oxidative stress that activates the NF‐κB pathway, leading to pyroptosis and immune dysfunction in grass carp CIK cells.

01 Nov 2024·Fish & Shellfish Immunology

Antibacterial activity of recombinant liver-expressed antimicrobial peptide-2 derived from olive flounder, Paralichthys olivaceus

Article

Author: Jeon, Yu-Jeong ; Im, Min-Hyuk ; Kim, Yeo-Reum ; Choi, Mi-Jin ; Byun, Jun-Hwan ; Lim, Han Kyu ; Kim, Jong-Myoung

Liver-expressed antimicrobial peptide-2 (LEAP-2) is a cysteine-rich peptide that plays a crucial role in the innate immune system of fish. To investigate the molecular function of LEAP-2 from olive flounder, Paralichthys olivaceus, we cloned the gene encoding LEAP-2 using PCR and expressed it in Escherichia coli. Analysis of LEAP-2 expression revealed predominant transcripts in the liver and lower levels in the intestine of olive flounder, whereas their expression levels in the liver and head kidney increased, during the initial stage of infection with the aquapathogenic bacterium Edwadrsiella piscicida. Recombinant LEAP-2 (rOfLEAP-2) purified from E. coli exhibited antimicrobial activity, as demonstrated by the ultrasensitive radial diffusion assay, against both Gram-positive (Bacillus subtilis, Streptococcus parauberis, and Lactococcus garvieae) and Gram-negative (Vibrio harveyi and E. coli) bacteria, with minimum inhibitory concentrations ranging from 25 to 100 μg/mL depending on the species tested. The antibacterial activity of rOfLEAP-2 was attributed to its ability to disrupt bacterial membranes, validated by the N-phenylnaphthalen-1-amine uptake assays and scanning electron microscope analysis against E. coli, V. harveyi, B. subtilis, and L. garvieae treated with rOfLEAP-2. Furthermore, a synergistic enhancement of antibacterial activity was observed when rOfLEAP-2 was combined with ampicillin or synthetic LEAP-1 peptide, suggesting a distinct mechanism of action from those of other antimicrobial agents. These findings provide evidence for the antibacterial efficacy of LEAP-2 from olive flounder, highlighting its potential therapeutic application against pathogenic bacteria.

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