Related Experiment Video

Updated: Jan 6, 2026

Multidisciplinary Approach to Obesity Management: A Case Report
05:10

Multidisciplinary Approach to Obesity Management: A Case Report

Published on: May 30, 2025

859

LEAP2 as a therapeutic target in obesity and cardiometabolic disorders

Stephanie K Holm1, Valdemar Brimnes Ingemann Johansen1, Christoffer Clemmensen2

  • 1Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Reviews in Endocrine & Metabolic Disorders
|November 24, 2025
PubMed

Insights

New research explores liver-expressed antimicrobial peptide 2 (LEAP2) as a potential therapy for obesity. LEAP2 targets the ghrelin receptor system (GHSR1a) to suppress appetite and may aid long-term weight management.

Area of Science:

  • Metabolic disorders
  • Endocrinology
  • Pharmacology

Background:

  • Obesity is a global health issue linked to cardiometabolic diseases.
  • Current weight-loss drugs often lead to weight regain after discontinuation.
  • The ghrelin receptor system (GHSR1a) is a target for appetite regulation, but drug development has faced challenges.

Purpose of the Study:

  • To review the therapeutic potential of the GHSR1a pathway for obesity and cardiometabolic disorders.
  • To highlight the role of liver-expressed antimicrobial peptide 2 (LEAP2) as a novel strategy.
  • To explore LEAP2's potential for long-term weight loss maintenance.

Main Methods:

  • Review of preclinical and clinical studies on the ghrelin receptor system and LEAP2.
  • Analysis of LEAP2's mechanism as a GHSR1a antagonist and inverse agonist.
  • Evaluation of LEAP2 analogs' metabolic effects in preclinical models.

Main Results:

  • LEAP2 suppresses appetite in rodents and humans.
  • Optimized LEAP2 analogs demonstrate promising preclinical metabolic effects.
  • LEAP2-based therapies may serve as adjunct treatments for sustained weight loss.

Conclusions:

  • The GHSR1a pathway, particularly with LEAP2, shows evolving therapeutic potential for obesity.
  • LEAP2 offers a novel strategy for managing obesity and associated cardiometabolic conditions.
  • LEAP2-based treatments may be valuable for long-term weight management support.
Keywords:
LEAP2AgRP neuronsAppetite regulationCardiometabolic disordersGHSRGhrelinLiver-expressed antimicrobial peptide 2Obesity

More Related Videos

White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice06:16

White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice

Published on: September 9, 2025

374
An Acupoint Catgut-embedding Therapy for Treating Obesity04:50

An Acupoint Catgut-embedding Therapy for Treating Obesity

Published on: April 4, 2025

1.1K

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
3.8K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
9.9K
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
149
Obesity01:24

Obesity

The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in...
1.1K
Regulation of Metabolism01:19

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
11.3K
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
809