Fat-Produced Adipsin Regulates Inflammatory Arthritis

Area of Science:

• Immunology
• Endocrinology
• Metabolic Research

Background:

• Inflammatory arthritis (IA) is often associated with obesity.
• The precise role of adipose tissue in IA pathogenesis remains unclear.
• Adipose tissue secretes various adipokines that may influence immune responses.

Purpose of the Study:

• To investigate the role of adipose tissue and its secreted factors in the development of inflammatory arthritis.
• To determine if the absence of fat impacts susceptibility to IA.
• To identify specific adipokines involved in IA pathogenesis.

Main Methods:

• Generation of "fat-free" (FF) mice lacking white and brown adipose tissue using diphtheria toxin.
• Induction of IA using K/BxN serum transfer in FF mice and control groups.
• Analysis of neutrophil counts, serum acute phase proteins, and joint pathology.
• Assessment of IA development in FF mice lacking specific adipokines (adiponectin, leptin, adipsin).
• Adipose tissue transplantation experiments between wild-type and adipsin-deficient mice.

Main Results:

• FF mice, despite systemic neutrophilia, were resistant to K/BxN serum-induced IA and bone destruction.
• Absence of adiponectin or leptin did not affect IA severity.
• Deletion of adipsin (complement factor D) completely prevented serum-induced IA.
• Transplantation of wild-type adipose tissue into FF mice restored IA susceptibility.
• Transplantation of adipsin-deficient fat into FF mice did not restore susceptibility.

Conclusions:

• Adipose tissue plays a critical regulatory role in the development of inflammatory arthritis.
• The adipokine adipsin, produced by adipocytes, is essential for susceptibility to K/BxN serum-induced IA.
• Adipose tissue-derived adipsin modulates systemic neutrophil responses, influencing joint inflammation.
• Targeting adipsin or the adipose-neutrophil axis may offer novel therapeutic strategies for IA.