Leptin Potentiates the Inflammatory Effect of Interleukin-1 Beta on Synoviocytes. Potential Preventive Role of DHA and EPA in Osteoarthritis Cell Model

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Atitaya Wayupat^1,a, Prachya Kongtawelert^1,b, Peraphan Pothacharoen^1,c, Thuzar Hla Shwe^2,d, and Thanyaluck Phitak^1,e*

¹Thailand Excellence Center for Tissue Engineering and Stem Cell, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

²Department of Chemistry, Texas A&M University, College Station, TX 77843-3255, USA

^* To whom correspondence should be addressed.

Received: March 27, 2025; Revised: May 6, 2025; Accepted: May 12, 2025

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A growing body of evidence indicates a high incidence of osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints in obese patients. The levels of leptin in the synovial fluid of obese patients with OA are elevated compared to healthy people, suggesting that leptin may be a key factor of OA in obese individuals. Synovitis can occur at all stages of OA development, causing diseases progression. We examined the effect of leptin on the inflammation in synoviocytes and demonstrated that leptin at its physiological concentration (1 ng/mL) promoted expressions of interleukin-6 (IL-6) and IL-8 in SW982 cells by activating p65, p38, JNK, STAT1, and STAT3. Moreover, the lowest pathological concentration of leptin potentiated the effect of IL-1β (main cytokine involved in OA pathogenesis) via activation of p65 and STAT3, leading to a significant upregulation of the IL-6 and IL-8 production. Pretreatment with omega-3 polyunsaturated fatty acids DHA and EPA suppressed the action of leptin and inhibited the IL-1β-mediated stimulation of synovitis by lowering the extent of p65 and STAT3 activation. According to our research, leptin may play a significant role in the development of OA in the joints of obese patients by promoting inflammation of synoviocytes through the activation of p65 and STAT3, while DHA and EPA, which inhibit activation of p65 and STAT3, can suppress the inflammation. Therefore, compounds that downregulate the activity of p65 and STAT3 may be the candidates for synovitis prevention and management in obese patients.

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KEY WORDS: osteoarthritis, leptin, obesity, IL-1β, synoviocyte, omega-3 fatty acids

DOI: 10.1134/S0006297925600863

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