The Involvement of Glucose and Lipid Metabolism Alteration in Rheumatoid Arthritis and Its Clinical Implication

Abstract

Obviously, immune cells like T cells and macrophages play a major role in rheumatoid arthritis (RA). On one hand, the breakdown of immune homeostasis directly induces systemic inflammation; on the other hand, these cells initiate and perpetuate synovitis and tissue damages through the interaction with fibroblast-like synoviocytes (FLS). In recent years, the pathological link between metabolic disorders and immune imbalance has received increasing attention. High energy demand of immune cells leads to the accumulation of metabolic byproducts and inflammatory mediators. They act on various metabolism-sensitive signal pathways as well as relevant transcription factors, such as HIF-1α, and STATs. These molecular events will impact RA-related effectors like circulating immune cells and joint-resident cells in return, allowing the continuous progression of systemic inflammation, arthritic manifestations, and life-threatening complications. In other words, metabolic complications are secondary pathological factors for the progression of RA. Therefore, the status of energy metabolism may be an important indicator to evaluate RA severity, and in-depth explorations of the mechanisms underlying the mystery of how RA-related metabolic disorders develop will provide useful clues to further clarify the etiology of RA, and inspire the discovery of new anti-rheumatic targets. This article reviews the latest research progress on the interactions between immune and metabolism systems in the context of RA. Great importance is attached to the changes in certain pathways controlling both immune and metabolism functions during RA progression.

Ginsenoside compound K plays an anti-inflammatory effect without inducing glucose metabolism disorder in adjuvant-induced arthritis rats

“…More and more studies are now showing that disturbed glucose metabolism promotes the development of RA. 10,11 Also with the improvement of people's living standards, the burden of metabolic diseases has increased most. 12 By observing the liver RNA-seq results, it was also found that AA rats had disturbed hepatic metabolism, although without hyperglycemia in the Model group.…”

Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization

“…However, biologic agents are expensive, and approximately 30–40% of patients do not respond well, accompanied with increased risk of infections. 4 , 5 Thus, novel therapeutic strategies for RA are urgently needed.…”

Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review

“…During FLS activation, metabolic changes are considered a key factor in their functional alteration ( 9 ). Multiple lines of evidence indicate that RA FLS cells exhibit considerable differences in protein, glucose, and lipid metabolism than normal synovial FLS cells ( 6 , 10 – 12 ). This abnormal metabolism is involved in RA pathogenesis, reflecting FLS adaptation to inflammatory and hypoxic conditions during excessive proliferation and phenotypic abnormalities.…”