Scholarlink

<p>Obesity is a global public health challenge intimately linked to cardiometabolic complications. Although current anti-obesity medications can produce substantial and rapid weight loss, their discontinuation often results in rapid weight regain, underscoring the urgent need for therapies that support long-term weight loss maintenance. The ghrelin receptor system, comprising the hormone ghrelin and its receptor growth hormone secretagogue receptor 1a (GHSR1a), has long been a target for appetite regulation, but decades of drug development have yielded limited clinical success. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous GHSR1a antagonist and inverse agonist, has reignited interest in this pathway. LEAP2 suppresses appetite in both rodents and humans, and optimized analogs have shown modest but promising metabolic effects in preclinical models. Although less potent than currently leading agents, LEAP2-based therapies may offer value as adjunct treatments, particularly for sustaining weight loss. This review explores the evolving therapeutic potential of the GHSR1a pathway, with a particular focus on LEAP2 as a novel strategy for treating obesity and associated cardiometabolic disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

LEAP2 as a therapeutic target in obesity and cardiometabolic disorders

  • 期刊论文

  • 发表日期：

    2025年11月24日

查看全文
  • Stephanie K. Holm,
  • Valdemar Brimnes Ingemann Johansen,
  • Christoffer Clemmensen

摘要

Obesity is a global public health challenge intimately linked to cardiometabolic complications. Although current anti-obesity medications can produce substantial and rapid weight loss, their discontinuation often results in rapid weight regain, underscoring the urgent need for therapies that support long-term weight loss maintenance. The ghrelin receptor system, comprising the hormone ghrelin and its receptor growth hormone secretagogue receptor 1a (GHSR1a), has long been a target for appetite regulation, but decades of drug development have yielded limited clinical success. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous GHSR1a antagonist and inverse agonist, has reignited interest in this pathway. LEAP2 suppresses appetite in both rodents and humans, and optimized analogs have shown modest but promising metabolic effects in preclinical models. Although less potent than currently leading agents, LEAP2-based therapies may offer value as adjunct treatments, particularly for sustaining weight loss. This review explores the evolving therapeutic potential of the GHSR1a pathway, with a particular focus on LEAP2 as a novel strategy for treating obesity and associated cardiometabolic disorders.