Ghrelin-LEAP2 interactions along the stomach-liver axis

Area of Science:

• Endocrinology
• Metabolism
• Molecular Biology

Background:

• Ghrelin, a stomach-produced peptide, stimulates food intake and growth hormone (GH) secretion, acting as an anabolic agent during starvation.
• Ghrelin exerts its effects by binding to the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor (GPCR).
• Anamorelin, a ghrelin agonist, is approved for cancer cachexia, highlighting ghrelin's therapeutic potential.

Purpose of the Study:

• To investigate the role of liver-expressed antimicrobial peptide (LEAP2) in regulating appetite and metabolism.
• To understand the interaction between ghrelin and LEAP2 at the GHSR.
• To explore the implications of these interactions in obesity and metabolic regulation.

Main Methods:

• Literature review and analysis of existing studies on ghrelin, LEAP2, and GHSR.
• Examination of data on LEAP2 upregulation in diet-induced obesity models.
• Analysis of correlations between serum LEAP2 concentrations and metabolic parameters like BMI, body fat, glucose, and triglycerides.

Main Results:

• LEAP2, initially identified as an antimicrobial peptide, antagonizes ghrelin's activity at the GHSR.
• LEAP2 expression is upregulated in the stomach following vertical sleeve gastrectomy in obese mice.
• Serum LEAP2 concentrations are positively correlated with obesity indicators (BMI, body fat) and metabolic dysfunction (glucose, triglycerides), while ghrelin levels are reduced in obesity.

Conclusions:

• Ghrelin and LEAP2 are key regulators of body weight, food intake, and glucose homeostasis through their opposing actions on the GHSR.
• LEAP2 emerges as a potential therapeutic target for obesity and related metabolic disorders.
• The balance between ghrelin and LEAP2 signaling at the GHSR is crucial for maintaining metabolic health.