Ghrelin receptor regulates adipose tissue inflammation in aging

Area of Science:

• Endocrinology
• Immunology
• Gerontology

Background:

• Aging is linked to low-grade adipose inflammation and insulin resistance.
• Ghrelin signaling, via the growth hormone secretagogue receptor (GHS-R), is implicated in obesity and insulin resistance.
• Macrophages in adipose tissue play a key role in inflammation, with M1 (pro-inflammatory) and M2 (anti-inflammatory) subtypes.

Purpose of the Study:

• To investigate the role of GHS-R in macrophage polarization within adipose tissue during aging.
• To determine if GHS-R ablation affects adipose tissue inflammation and insulin sensitivity in aged mice.

Main Methods:

• Utilized aged Ghsr(-/-) mice and wild-type littermates.
• Analyzed macrophage infiltration, M1/M2 ratio, and cytokine expression in white and brown adipose tissues.
• Assessed peritoneal macrophage function and norepinephrine production.
• Examined cell-autonomous effects of GHS-R in macrophages using GHS-R antagonists and LPS stimulation.

Main Results:

• GHS-R ablation in aged mice promoted a shift towards anti-inflammatory M2 macrophages.
• Reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokines were observed in adipose tissues of old Ghsrp(-/-) mice.
• Peritoneal macrophages from old Ghsrp(-/-) mice showed increased norepinephrine production, consistent with M2 polarization.
• GHS-R antagonists suppressed LPS-induced inflammatory responses in macrophages, indicating cell-autonomous effects.

Conclusions:

• Ghrelin signaling through GHS-R significantly influences macrophage polarization in adipose tissue during aging.
• Targeting GHS-R may offer a therapeutic strategy for age-associated adipose inflammation and insulin resistance.