Polymicrobial Infection Induces Adipose Tissue Dysfunction via Gingival Extracellular Vesicles.

Area of Science:

• Oral Biology
• Metabolic Disease
• Cell Biology

Background:

• Periodontitis is linked to metabolic dysregulation and insulin resistance.
• The mechanisms connecting periodontitis to adipose tissue dysfunction require further investigation.
• Extracellular vesicles (EVs) mediate intercellular communication and may link periodontitis to insulin resistance.

Purpose of the Study:

• To investigate the impact of polymicrobial oral infection on white adipose tissue (WAT) function.
• To explore the role of gingival EVs (gEVs) in mediating periodontitis-induced WAT dysfunction.

Main Methods:

• Mice were infected orally with *Porphyromonas gingivalis* and *Fusobacterium nucleatum* for 14 weeks.
• WAT function was assessed by measuring key signaling molecules and gene expression.
• Gingival EVs (gEVs) were isolated, characterized, and their microRNA content analyzed via RNA sequencing.
• In vitro and in vivo experiments were conducted to evaluate the effects of gEVs on WAT.

Main Results:

• Prolonged oral infection induced WAT dysfunction, evidenced by reduced AKT phosphorylation, adiponectin, and leptin levels, and altered adipogenesis/lipogenesis gene expression.
• RNA sequencing of gEVs revealed differentially expressed microRNAs involved in insulin signaling and adipose tissue function.
• Gingival EVs (gEVs) from infected mice functionally mimicked plasma-derived EVs and induced WAT dysfunction in healthy recipient mice.

Conclusions:

• Polymicrobial oral infection significantly impairs white adipose tissue (WAT) function.
• Gingival EVs (gEVs) represent a novel mechanism by which periodontal infections can affect systemic metabolic health.
• Targeting gEVs may offer therapeutic potential for managing metabolic complications associated with periodontitis.