Liver-expressed antimicrobial peptide 2

experimental

Also known as: LEAP2, Q969E1

Liver-expressed antimicrobial peptide 2 (LEAP2) is a cysteine-rich cationic peptide primarily produced in the liver and small intestine. Its mechanism of action involves direct antimicrobial activity against Gram-positive and Gram-negative bacteria, mediated by membrane disruption and pore formation. Additionally, LEAP2 functions as an endogenous antagonist of the ghrelin receptor (GHSR1a), competitively inhibiting ghrelin signaling, which links it to metabolic regulation beyond its antimicrobial role. Key research findings demonstrate that LEAP2 exhibits broad-spectrum bactericidal effects *in vitro*, particularly against pathogens such as *Escherichia coli* and *Staphylococcus aureus*. Its expression is upregulated in response to bacterial infection and inflammatory stimuli, suggesting a role in host defense. Recent studies also highlight LEAP2's involvement in energy homeostasis, as its antagonism of ghrelin reduces food intake and modulates glucose metabolism in animal models. However, its precise physiological significance and therapeutic potential remain under investigation. Clinically, LEAP2 is being explored as a potential biomarker for metabolic disorders, including obesity and type 2 diabetes, due to its inverse correlation with ghrelin activity. Its antimicrobial properties may also inform novel antibiotic strategies, though no approved therapies exist. Further research is needed to validate its translational applications. For research purposes only — not medical advice.

Key data

Category
Immune Modulation
Sequence
MWHLKLCAVLMIFLLLLGQIDGSPIPEVSSAKRRPRRMTPFWRGVSLRPIGASCRDDSECITRLCRKRRCSLSVAQE
Molecular weight
8814 g/mol
Research status
experimental
References
179
Tags
uniprot, 3d-structure, antibiotic, antimicrobial, cleavage-on-pair-of-basic-residues, disulfide-bond, proteomics-identification, reference-proteome, secreted, signal

Mechanism of action

Has an antimicrobial activity

Research & studies

Liver-expressed antimicrobial peptide 2 (LEAP2)
Trends in endocrinology and metabolism: TEM · 2025 · PubMed
Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice
Diabetes · 2025 · PubMed

LA-LEAP2 lowered body weight in obese mice by reducing energy intake and preserving energy expenditure.; Combination of LA-LEAP2 and semaglutide showed superior weight reduction in some experiments compared to semaglutide monotherapy.; The combination therapy attenuated weight regain more effectively than semaglutide alone.; No signs of discomfort or behavioral aversion were detected following LA-LEAP2 administration.

Peptide with Dual Roles in Immune and Metabolic Regulation: Liver-Expressed Antimicrobial Peptide-2 (LEAP-2)
Molecules (Basel, Switzerland) · 2025 · PubMed
The Concentration of Liver-Expressed Antimicrobial Peptide 2 in Human Milk and Infant Plasma Is Positively Associated with Adiposity and Body Weight in the First Year of Life
The Journal of nutrition · 2024 · PubMed
Antibacterial activity of recombinant liver-expressed antimicrobial peptide-2 derived from olive flounder, Paralichthys olivaceus
Fish & shellfish immunology · 2024 · PubMed

rOfLEAP-2 showed antimicrobial activity against Gram-positive (B. subtilis, S. parauberis, L. garvieae) and Gram-negative (V. harveyi, E. coli) bacteria.; Antibacterial mechanism involves disruption of bacterial membranes, confirmed by uptake assays and SEM.; Synergistic enhancement of activity when combined with ampicillin or synthetic LEAP-1 peptide.; LEAP-2 expression increased in liver and head kidney during early infection with E. piscicida.

Liver-expressed antimicrobial peptide 2 is a hepatokine regulated by ghrelin, nutrients, and body weight
Scientific reports · 2024 · PubMed
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome
Genome medicine · 2024 · PubMed

32 proteins were identified as potential therapeutic targets for CKD and kidney function across diverse datasets and clinical types.; Five novel proteins (GCKR, IGFBP-5, sRAGE, GNPTG, YOD1) were confirmed by MR, SMR, and colocalization analyses.; The identified proteins interact and are enriched in immunity-related pathways, with tissue- and cell-type specificity.; Findings offer potential targets for developing immunotherapies, combination therapies, or targeted interventions for CKD.

Identification of antibacterial activity of liver-expressed antimicrobial peptide 2 (LEAP2) from primitive vertebrate lamprey
Fish & shellfish immunology · 2024 · PubMed

Frequently asked questions

What is Liver-expressed antimicrobial peptide 2?

Liver-expressed antimicrobial peptide 2 (LEAP2) is a cysteine-rich cationic peptide primarily produced in the liver and small intestine. Its mechanism of action involves direct antimicrobial activity against Gram-positive and Gram-negative bacteria, mediated by membrane disruption and pore formation. Additionally, LEAP

How does Liver-expressed antimicrobial peptide 2 work?

Has an antimicrobial activity

What is the research status of Liver-expressed antimicrobial peptide 2?

Liver-expressed antimicrobial peptide 2 is currently classified as experimental, with 179 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Liver-expressed antimicrobial peptide 2?

Liver-expressed antimicrobial peptide 2 has a molecular weight of approximately 8814 g/mol.

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