Emerging role of leptin in joint inflammation and destruction

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Consistent with the early stages of RA, these pathogenic cells cooperate and activate each other directly by cellto-cell contact or indirectly via humoral factors. Recently, growing evidence has revealed essential role of adipokines, which are multifunctional signal transduction molecules, in the immune system. In this review, we summarize the current understanding of the cross-talk between leptin, one of the most well-known and best-characterized adipokines, and osteoimmunology. Furthermore, we discuss the contribution of leptin to the pathogenesis of RA and its potential mechanisms.

Levels of TNF-α and Soluble TNF Receptors in Normal-Weight, Overweight and Obese Patients with Dilated Non-Ischemic Cardiomyopathy: Does Anti-TNF Therapy Still Have Potential to Be Used in Heart Failure Depending on BMI?

“…In our study, adiponectin was inversely related to CRP in obesity, but, surprisingly, leptin was inversely related to CRP in normal-weight patients. These unexpected results do not align with most previous observations [ 58 , 59 ]; however, a few investigators have noticed a similar correlation between leptin and CRP [ 60 , 61 , 62 ]. Consequently, this is an area for further research.…”

Organokines in Rheumatoid Arthritis: A Critical Review

“…Its production is controlled by food intake, sex hormones, energy status, and inflammatory mediators. Leptin can also modulate both the innate and adaptive immune systems by activating proliferation and activation of macrophages and monocytes, regulating the cytotoxicity of natural killer cells, modulating neutrophils chemotaxis, and controlling T CD4, Th1 (T helper 1), and Th2 (T helper 2) cells’ phenotypes [ 11 , 99 , 100 , 101 ].…”

“…Leptin also modulates inflammation through JAK2/STAT3, NF-kB, and activating protein-1 (AP-1) pathways, maintaining positive correlations mainly with IL-17 in plasma and IL-6 and IL-8 in the synovial fluid of RA patients. Adhesion molecule production was also stimulated by leptin in human chondrocytes through JAK2, PI3K, and MAPK signaling pathways, which potentializes leukocyte invasion in inflamed joints [ 85 , 99 , 100 , 102 , 103 ].…”

Obesity and consequent changes in the body

“…Gojaznost je prepoznata kao hronično inflamatorno stanje niskog stepena i proupalni citokini doprinose razvoju insulinske rezistencije. Rezultati nekih ispitivanja pokazali su prisustvo pozitivne korelacije između ekspresije leptina u masnom tkivu i markera upale, pa se čini da je okruženje u masnom tkivu takvo da hiperleptinemija ima potencijal da pospeši zapaljenje i indirektno utiče na metabolizam adipocita (21). Koncentracija cirkulišućeg leptina je u opsegu od 0.2 do 5 nmol (3-8 ng/ml).…”