Abstract

The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA). Some studies have shown that the three compositions of adipose tissue (white, brown, and beige) have different functions. Brown adipose tissue (BAT) is known to secrete several factors that differ from those in white adipose tissue. This suggests that BAT might have potential positive advantages in the physiology of autoimmune diseases. We compared the functions of collagen-induced arthritis mice-derived BAT (CIA BAT) with normal mice-derived BAT. DBA/1J mice (6–7 weeks of age) were immunized by intradermal injection at the base of the tail with 100 μg of bovine type II collagen (CII) emulsified in complete Freund’s adjuvant. Immunized mice then received booster immunizations by intraperitoneal injection with 100 μg of CII in incomplete Freund’s adjuvant. We transplanted CIA BAT and normal BAT into CIA recipient mice. After transplantation, we measured the functions of CIA BAT and normal BAT in mice. Normal BAT-transplanted mice showed significantly lower scores of bone damage, inflammation, and cartilage damage. The proinflammatory cytokines in normal BAT-transplanted mice, such as IL-12, IL-17, IL-6, and tumor necrosis factor-α (TNF-α), tended to decrease. Microarray analysis showed that the PI3K-AKT signaling pathway and IL-17 levels of CIA BAT tissues were significantly higher than those of normal BAT tissues. These results suggest that the transplantation of normal brown fat may have a therapeutic effect in RA patients.

Highlights

  • The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA)

  • It is well known that obese people and animals have high levels of proinflammatory cytokines, such as serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL)-1β, IL-6, and IL-17 all of which are produced by macrophages derived from adipose t­ issue[4,5]

  • Epididymal white adipose tissues, normal Brown adipose tissue (BAT) which was acquired to control mouse and BAT which was derived from collagen-induced arthritis (CIA) mouse (CIA BAT) were showed (Fig. 1B)

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Summary

Introduction

The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA). Brown adipose tissue (BAT) is known to secrete several factors that differ from those in white adipose tissue. This suggests that BAT might have potential positive advantages in the physiology of autoimmune diseases. The proinflammatory cytokines in normal BAT-transplanted mice, such as IL-12, IL-17, IL-6, and tumor necrosis factor-α (TNF-α), tended to decrease. Microarray analysis showed that the PI3K-AKT signaling pathway and IL-17 levels of CIA BAT tissues were significantly higher than those of normal BAT tissues. These results suggest that the transplantation of normal brown fat may have a therapeutic effect in RA patients. We injected CIA mice with CIA BAT or normal BAT and evaluated the therapeutic role of normal BAT in CIA mice

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