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The next big LEAP2 understanding ghrelin function.

The Journal of Clinical Investigation

|August 20, 2019

Summary

This summary is machine-generated.

Plasma liver-enriched antimicrobial peptide-2 (LEAP2) levels regulate ghrelin sensitivity. Lower LEAP2 during fasting enhances ghrelin

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Area of Science:

Metabolism and Endocrinology
Hormonal Regulation
Obesity and Weight Management

Background:

Ghrelin is a primary hormone regulating energy homeostasis, influencing appetite and energy storage.
Organismal metabolic status, such as fasting or obesity, affects sensitivity to ghrelin's actions.
The precise mechanisms controlling ghrelin sensitivity remain largely undefined.

Purpose of the Study:

To investigate the role of liver-enriched antimicrobial peptide-2 (LEAP2) in modulating ghrelin sensitivity.
To elucidate the relationship between LEAP2 and acyl-ghrelin levels in different metabolic states.
To understand how LEAP2 influences ghrelin's effects on energy balance.

Main Methods:

Measurement of plasma LEAP2 and acyl-ghrelin levels in mice and humans.
Correlation analysis of hormone levels under conditions of energy deficit and energy surplus.
Assessment of LEAP2's impact on ghrelin receptor antagonism.

Main Results:

Plasma LEAP2 levels were inversely correlated with plasma acyl-ghrelin in both energy deficit and surplus states.
A decrease in plasma LEAP2 during fasting potentiated the effects of acyl-ghrelin.
Elevated LEAP2 levels in obesity were found to suppress acyl-ghrelin's actions.

Conclusions:

LEAP2 acts as a key regulator of ghrelin sensitivity by antagonizing the ghrelin receptor.
Dynamic changes in LEAP2 levels in response to metabolic status fine-tune ghrelin signaling.
This discovery offers potential therapeutic targets for weight maintenance and metabolic disorders.