Association of Leptin Levels and Disease Activity in Patients with Early Rheumatoid Arthritis

Taylan, Ali; Akıncı, Barış; Toprak, Burak; Bırlık, Merih; Arslan, Fatma Demet; Ekerbiçer, Hasan Çetin; Gündoğdu, Barış; Çolak, Ayfer; Engin, Bahar

doi:10.1016/j.arcmed.2021.02.002

Cited by 9 publications

(10 citation statements)

References 56 publications

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“…However, Wang et al showed that leptin-JAK/STAT3 promoted breast cancer stemness and chemoresistance via upregulating lipid metabolism through FAO [19], providing new light to better understanding of the role of lipid metabolic reprogramming. Our and other's studies have found that leptin is elevated in RA serum and synovial fluid and correlated to disease activity [37]. Our previous researches still showed that leptin could elevate RA peripheral CD4 + CXCR5 + ICOS + Tfh production via IL-6 secretion through STAT1 and STAT3 pathways [20].…”

Section: Discussionmentioning

confidence: 81%

Elevated fatty acid β-oxidation by leptin contributes to the proinflammatory characteristics of fibroblast-like synoviocytes from RA patients via LKB1-AMPK pathway

et al. 2023

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Fibroblast-like synoviocytes (FLS) maintain chronic inflammation leading to joint destruction in rheumatoid arthritis (RA). Fatty acid β-oxidation (FAO) regulates cell function. Here, we aimed to investigate the effect of FAO enhanced by leptin on the characteristics of RA-FLS and elucidate the potential metabolic mechanism. Key enzymes involved in lipid metabolism were detected with qPCR in HSF, MH7A cell line and isolated RA-FLS treated with RA or healthy control (HC) serum. In some experiments, FAO inhibitor, etomoxir (ETO) or anti-leptin antibody were added into serum-treated RA-FLS. In other experiments, RA-FLS were stimulated with leptin together with ETO or AMP-activated protein kinase (AMPK) inhibitor compound C (CC) or silencing liver kinase B1 (LKB1). Cell proliferation, proinflammatory factor production, pro-angiogenesis, chemoattractive potential, FAO-related key enzymes, AMPK and LKB1 in FLS were analyzed. FAO-related key enzymes were evaluated in serum-treated RA-FLS with or without anti-leptin antibody. Related functions of leptin-stimulated RA-FLS were examined in the presence or absence of ETO. AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1) in leptin-stimulated RA-FLS were tested with western blot. Activation of AMPK in leptin-stimulated RA-FLS was detected after silencing LKB1. We found that MH7A cell line and RA serum-treated FLS exhibited upregulated FAO, and ETO could inhibit the proinflammatory phenotypes of RA-FLS. The addition of anti-leptin antibody suppressed the elevation of FAO mediated by RA serum. More importantly, leptin promoted the proinflammatory characteristics of RA-FLS, which was reversed by ETO. Leptin activated AMPK by upregulating LKB1. CC impaired leptin-induced CPT-1A expression in RA-FLS. Our study uncovers that elevated FAO mediated by leptin drives abnormal function of RA-FLS and suggests leptin or FAO inhibition may serve as a promising therapeutic strategy for RA.

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Section: Discussionmentioning

confidence: 81%

Elevated fatty acid β-oxidation by leptin contributes to the proinflammatory characteristics of fibroblast-like synoviocytes from RA patients via LKB1-AMPK pathway

et al. 2023

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“…The studies included in this review are from Italy [ 13 ], Egypt [ 14 , 15 , 16 ], Unites States [ 17 , 18 ], Mexico [ 19 , 20 , 21 , 22 ], Sweden [ 23 , 24 ], China [ 25 , 26 , 27 ], Turkey [ 28 ], and Finland [ 29 ]. One study was multicentered [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…Taylan et al [ 28 ] also conducted an analytical cohort study with 47 RA and 25 control individuals to assess leptin serum levels associated with RA disease activity. The results demonstrated that the higher leptin serum levels were, the higher the disease activity also was.…”

Section: General Aspects Of Ra and The Role Of Myokines Osteokines Ad...mentioning

confidence: 99%

Organokines in Rheumatoid Arthritis: A Critical Review

Laurindo

Maio

Barbalho

et al. 2022

IJMS

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Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects the joints. Organokines can produce beneficial or harmful effects in this condition. Among RA patients, organokines have been associated with increased inflammation and cartilage degradation due to augmented cytokines and metalloproteinases production, respectively. This study aimed to perform a review to investigate the role of adipokines, osteokines, myokines, and hepatokines on RA progression. PubMed, Embase, Google Scholar, and Cochrane were searched, and 18 studies were selected, comprising more than 17,000 RA patients. Changes in the pattern of organokines secretion were identified, and these could directly or indirectly contribute to aggravating RA, promoting articular alterations, and predicting the disease activity. In addition, organokines have been implicated in higher radiographic damage, immune dysregulation, and angiogenesis. These can also act as RA potent regulators of cells proliferation, differentiation, and apoptosis, controlling osteoclasts, chondrocytes, and fibroblasts as well as immune cells chemotaxis to RA sites. Although much is already known, much more is still unknown, principally about the roles of organokines in the occurrence of RA extra-articular manifestations.

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“…Ambiguous results were also reported regarding the association of leptin concentrations with disease activity. Serum leptin levels were significantly higher in RA patients with high disease activity compared to those with lower activity and were associated with DAS28 and CRP levels [ 85 , 86 , 93 , 94 , 95 ]. In contrast, many studies reported a lack of correlation between leptin amounts and disease activity [ 84 , 87 , 91 ].…”

Section: Leptin and Rheumatoid Arthritismentioning

confidence: 99%

Leptin in Osteoarthritis and Rheumatoid Arthritis: Player or Bystander?

Eldjoudi

Cordero-Barreal

González-Rodríguez

et al. 2022

IJMS

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White adipose tissue (WAT) is a specialized tissue whose main function is lipid synthesis and triglyceride storage. It is now considered as an active organ secreting a plethora of hormones and cytokines namely adipokines. Discovered in 1994, leptin has emerged as a key molecule with pleiotropic functions. It is primarily recognized for its role in regulating energy homeostasis and food intake. Currently, further evidence suggests its potent role in reproduction, glucose metabolism, hematopoiesis, and interaction with the immune system. It is implicated in both innate and adaptive immunity, and it is reported to contribute, with other adipokines, in the cross-talking networks involved in the pathogenesis of chronic inflammation and immune-related diseases of the musculo-skeletal system such as osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the most recent findings concerning the involvement of leptin in immunity and inflammatory responses in OA and RA.

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Association of Leptin Levels and Disease Activity in Patients with Early Rheumatoid Arthritis

Cited by 9 publications

References 56 publications

Elevated fatty acid β-oxidation by leptin contributes to the proinflammatory characteristics of fibroblast-like synoviocytes from RA patients via LKB1-AMPK pathway

Elevated fatty acid β-oxidation by leptin contributes to the proinflammatory characteristics of fibroblast-like synoviocytes from RA patients via LKB1-AMPK pathway

Organokines in Rheumatoid Arthritis: A Critical Review

Leptin in Osteoarthritis and Rheumatoid Arthritis: Player or Bystander?

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