Analysis of Hepatic Lipid Metabolism and Immune Function During the Development of Collagen-Induced Arthritis

Abstract

The liver is essential for metabolic and immune functions and has been linked to systemic inflammatory diseases. However, the role of the liver is still elusive during the development of rheumatoid arthritis (RA), although there have been indeed some reports. We used label-free quantitative proteomics and experimental verification in this study to reveal the hepatic lipid metabolism and immune function during collagen-induced arthritis (CIA) development. The proteomics results revealed that the role of the liver differs in different phases of CIA rats. In terms of specific performance, hepatic lipid metabolism, which is primarily concerned with cholesterol, triacylglycerol, and phospholipid, was significantly influenced in the CIA induction phase, whereas the immune function, which includes binding of granulocytes, adhesion of immune cells, etc., was affected considerably at the peak phase of CIA rats compared to normal rats. Finally, the hepatic dynamic changes in CIA rats were further confirmed using targeted metabolomics and ELISA. We found that most fatty acids of the liver in the CIA induction phase were significantly decreased, and proteins related to complement activation and migration or adhesion of immune cells including C3, MMP-8, CTSZ, and S100A9 were significantly increased in the liver of CIA rats in the peak phase. Our findings indicated that the lipid metabolism and immune function of the liver were influenced in CIA rats. Thus, the conditions of the liver during RA development should be considered in therapeutic and nutritional interventions.