The adipocyte apolipoprotein M is negatively associated with inflammation

Area of Science:

• Biochemistry
• Immunology
• Metabolic Health

Background:

• Obesity is linked to adipose tissue (AT) and systemic inflammation, with most adipokines being pro-inflammatory.
• Apolipoprotein M (APOM) is an adipokine downregulated in obesity, associated with metabolically healthy AT.

Purpose of the Study:

• To investigate the role of adipose-derived APOM in mitigating obesity-associated AT inflammation.
• To assess APOM's impact on inflammatory gene expression in human and mouse models.

Main Methods:

• Correlational analysis of AT APOM mRNA and hs-CRP in 300 obese individuals.
• Assessment of inflammatory profiles in apolipoprotein M knockout (Apom^-/-) and wild-type (WT) mice on normal chow (NCD) and high-fat diets (HFD).
• In vivo and in vitro experiments using adeno-associated viruses for APOM overexpression in mouse AT and human adipocytes, followed by macrophage co-culture.

Main Results:

• In obese humans, AT APOM mRNA negatively correlated with plasma hs-CRP.
• HFD induced AT and liver inflammation and reduced Apom gene expression in mice.
• Apom deficiency exacerbated AT inflammation in mice, while APOM overexpression in mouse AT reduced it.
• APOM-enriched media from adipocytes decreased inflammatory gene expression (IL6, MCP1) in macrophages.

Conclusions:

• Adipocyte-derived APOM plays a protective role against obesity-induced adipose tissue inflammation.
• APOM may represent a therapeutic target for managing obesity-related inflammatory conditions.