Ghrelin effects on mitochondrial fitness modulates macrophage function

Area of Science:

• Immunology
• Cellular Metabolism
• Endocrinology

Background:

• Systemic cues regulating cellular metabolism influence immune responses.
• Ghrelin, an orexigenic hormone, has known immunoregulatory roles but its mechanism in macrophages is unclear.

Purpose of the Study:

• To investigate if ghrelin alters macrophage metabolism to modulate their function.
• To explore the role of mitochondrial function in ghrelin's effects on macrophages.

Main Methods:

• Assessed cytokine secretion (TNF-α, IL-1β, IL-12) in LPS-activated peritoneal macrophages.
• Measured mitochondrial membrane potential and respiratory rate.
• Investigated the impact of glucose deprivation, pyruvate transport inhibition, and mitofusin-2 deficiency on ghrelin's effects.

Main Results:

• Ghrelin inhibited TNF-α and IL-1β secretion, and increased IL-12 production in LPS-activated macrophages.
• Ghrelin enhanced mitochondrial membrane potential, respiratory rate, and prevented mitochondrial damage.
• Ghrelin suppressed LPS-induced glycolysis and its IL-12 enhancing effect was dependent on mitochondrial function and elongation.

Conclusions:

• Ghrelin modulates macrophage function through alterations in mitochondrial metabolism.
• Mitochondrial integrity and function are crucial for ghrelin's immunomodulatory effects, particularly IL-12 production.