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The important role of adipokines. Adipokines are produced mainly by adipocytes and play critical roles in several major disorders including insulin sensitivity, cardiovascular disease, arthritic conditions (i.e., RA and OA), and obesity.
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Secretion from adipose tissue of adipokines or adipocytokines, comprising of bioactive peptides or proteins, immune molecules and inflammatory mediators, exert critical roles in inflammatory arthritis and obesity. This review considers the evidence generated over the last decade regarding the effects of several adipokines including leptin, adiponec...
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Context 1
... tissue secretes various bioactive peptides or proteins, immune molecules and inflammatory mediators known as adipokines (only produced by the adipose tissue) or adipocytokines (mainly, but not solely, produced by adipocytes) (Figure 1). In this review, the term "adipokine" refers to these multifunctional molecules. ...
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Due to their multidirectional influence, adipocytokines are currently the subject of numerous intensive studies. Significant impact applies to many processes, both physiological and pathological. Moreover, the role of adipocytokines in carcinogenesis seems particularly interesting and not fully understood. For this reason, ongoing research focuses...
The objective of this study was to assess the value of serum leptin, adiponectin, apelin, and ghrelin as biomarkers for the prediction and diagnosis of intra-hepatic cholestasis (ICP). This prospective study included pregnant women in the third trimester of pregnancy: 63 with ICP, 48 and 15 of whom had mild and severe disease, respectively, and 32...
Background and aims:
Association of serum and salivary adiponectin, apelin, visfatin and vaspin were studied in type 2 diabetes (T2DM) among Asian Indians. Their concentrations in periodontitis were also studied.
Methods:
In this cross-sectional analysis, men and women aged ≥35 years, with no history of diabetes, were screened for ≥3 risk factor...
Citations
... Adipokines have been demonstrated to play a pivotal role in joint homeostasis by modulating anabolic and catabolic balance, autophagy, apoptosis and inflammatory responses (16,17). In addition, the adipokines modulate subchondral bone turnover and chondrophyte and osteophyte formation. ...
Osteoartritis (OA) is a debilitating disease affecting both humans and animals. In the early stages, OA is characterized by damage to the extracellular matrix (ECM) and apoptosis and depletion of chondrocytes. OA progression is characterized by hyaline cartilage loss, chondrophyte and osteophyte formation, thickening of the joint capsule and function loss in the later stages. As the regenerative potential of cartilage is very limited and osteoarthritic changes are irreversible, prevention of OA, modulation of existing osteoarthritic joint inflammation, reducing joint pain and supporting joint function are the only options. Progression of OA and pain may necessitate surgical intervention with joint replacement or arthrodesis as end-stage procedures. In human medicine, the role of adipokines in the development and progression of OA has received increasing interest. At present, the known adipokines include leptin, adiponectin, visfatin, resistin, progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin. Adipokines have been demonstrated to play a pivotal role in joint homeostasis by modulating anabolic and catabolic balance, autophagy, apoptosis and inflammatory responses. In small animals, in terms of dogs and cats, naturally occurring OA has been clearly demonstrated as a clinical problem. Similar to humans, the etiology of OA is multifactorial and has not been fully elucidated. Humans, dogs and cats share many joint related degenerative diseases leading to OA. In this review, joint homeostasis, OA, adipokines and the most common joint diseases in small animals leading to naturally occurring OA and their relation with adipokines are discussed. The purpose of this review is highlighting the translational potential of OA and adipokines research in small animal patients.
... This could be secondary to the lack of physical activity due to joint pain, stiffness, fatigue or other short or long-term disease-related disabilities [12,23]. In addition, it has been demonstrated that JIA children with obesity had higher levels of inflammatory mediators such as C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 1 (IL-1), and tumor necrosis factor α (TNF-α) than normal weight children with JIA [24,25]. Moreover, it should be noted that low-grade inflammation represents a hallmark of obesity, as largely demonstrated [26,27]. ...
... Indeed, mounting evidence has supported the role of adipose tissue as an active immune organ secreting various immunomodulatory factors [22,25] including various adipokines (e.g. leptin, resistin, vaspin) and cytokines such as TNF-α, IL-6, IL-1 [24], which in turn might be responsible for a high disease activity in JIA patients with obesity [8,20,24]. ...
... Indeed, mounting evidence has supported the role of adipose tissue as an active immune organ secreting various immunomodulatory factors [22,25] including various adipokines (e.g. leptin, resistin, vaspin) and cytokines such as TNF-α, IL-6, IL-1 [24], which in turn might be responsible for a high disease activity in JIA patients with obesity [8,20,24]. ...
Despite the well-known role of obesity as risk factor for Juvenile Idiopathic Arthritis (JIA) severity, emerging but limited evidence suggested a similar role for underweight. We investigated the role of body mass index (BMI) across its full spectrum in a cohort of children with JIA.
We retrospectively studied 113 children with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. The patients underwent a comprehensive evaluation including both clinical and biochemical assessments. According to BMI Z-score, the cohort was divided into five groups as underweight, normal weight, overweight (OW), obesity (OB), and severe OB. Disease activity was calculated by Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count and relapses were defined according to Wallace criteria.
The mean age of the cohort was 7.43 ± 4.03 years. The prevalence of underweight, normal weight, OW, OB, and severe OB was 7.2%, 54.1%, 10.8%, 17.1%, and 10.8%, respectively. Significant higher ferritin levels and erythrocyte sedimentation rate values were found in patients with severe OB and underweight compared to subjects belonging to normal weight, OW, and OB groups. A greater JADAS-10 score was observed in underweight patients and in those with severe OB than other groups. The relapse rate was higher in patients with severe OB and underweight compared to other groups.
Conclusions: Both underweight and OB might negatively affect JIA course. Weight control is fundamental in children with JIA to avoid a more unfavourable course of the disease.
What is Known:
• Obesity represents a well-known risk factor for JIA severity.
• The role of underweight in children with JIA is still poorly explored.
What is New:
• As observed in children with obesity, underweight young patients with JIA seem to experience a more severe JIA course.
• Healthy lifestyle promotion in children with JIA is a crucial step in the management of the disease.
... 18 Some researchers have found verifiable positive correlations between serum resistin levels and both CDAI and inflammatory status according to ESR, and CRP in RA patients. 19 Some studies alleged that resistin in chronic inflammatory states like RA, could compete with lipopolysaccharide for binding to (Tolllike receptor-4) and may serve as a pro-inflammatory cytokine in human monocytes. According to subsequent research, resistin serum levels are positively correlated with CRP levels in RA, indicating that these hormones serve as pro-inflammatory cytokines in this condition. ...
Objective: The current study aimed to evaluate RA patients’ serum resistin levels and to observe the relationshipbetween disease activity and resistin.Methods: A case-control study was conducted on (100) RA Iraqi patients during treatment with bDMARDs. The firstgroup of 50 patients received etanercept, and the second group of 50 patients were on Rituximab (RTX). The controlgroup comprised of 50 healthy individuals. ELISA was used to evaluate serum Resistin in and anti-CRP. Inflammatorymarkers ESR, and CRP with biochemical tests were conducted. In addition to estimating Clinical Disease Activity scoreI(CDAI) by the physicians; at Baghdad Teaching Hospital.Results: Levels of Resistin of RA treated with RTX were significantly higher (16.30 ± 7.38ng/ml) than in RA treated withETN (10.61±5.85ng/ml) compared to the control group. (6.95±1.70 ng/ml). The resistin level showed a positivecorrelation with Anti-CCP abs which was considered to have a high positive correlation (p< 0.01) in ETN group. Whilethis correlation was lower than the RTX group, the, correlation between resistin, and ESR was the highest in RTX groupwhilst no such correlation was observed in the ETN group. There was a positive correlation with CDAI of RA subgroups(moderate activity (p<0.05), and high activity (p<0.001). The logistic regression of resistin was associated with biologicaltreatment, odds ratio was (OR=1.138, p-value= 0.014, 95% CI.1.025-1.257) during ETN, and RTX independent of CRP.Conclusion: There is an association between serum RSN and anti CRP as a result of disease activity independent ofCRP. resist in levels can be used to determine disease activity to avoid disease progression and erosion.Keywords: Protein, Antibodies, Etanercept, Rituximab, Disease, Physicians
... Leptin is a pleiotropic peptide hormone [16] produced by tissues such as fat and cartilage. Early studies found that it mainly affects energy metabolism in the central system [17]. Still, now it has been found that Leptin also has a dual role as a hormone and cytokine, participating in the regulation of several processes such as the inflammatory response, immune homeostasis, cartilage and bone metabolism, bone formation, angiogenesis, wound healing, and intestinal nutrient absorption [18]. ...
Objective
Acupuncture has become a popular complementary treatment in oncology. This study is based on RNA-Seq transcriptome sequencing technology to investigate the molecular mechanisms underlying the effect of acupuncture-mediated regulation of the Leptin/AMPK signaling pathway on mitochondrial dysfunction-induced fatigue in breast cancer patients after chemotherapy.
Methods
Peripheral blood samples from 10 patients with post-operative chemotherapy for breast cancer were selected for transcriptome sequencing to screen the key molecular pathways involved in fatigue after chemotherapy in breast cancer patients. Besides, peripheral blood samples were collected from 138 post-operative chemotherapy patients with breast cancer to study the composite fatigue and quality of life scores. Flow cytometry was used to detect T lymphocyte subsets in peripheral blood-specific immune cells. In addition, a blood cell analyzer was used to measure peripheral blood leukocyte counts, and MSP-PCR was used to detect mitochondrial DNA mutations in peripheral blood leukocytes.
Results
Transcriptome bioinformatics analysis screened 147 up-regulated mRNAs and 160 down-regulated mRNAs. Leptin protein was confirmed as the key factor. Leptin was significantly higher in the peripheral blood of breast cancer patients who developed fatigue after chemotherapy. Acupuncture treatment effectively improved post-chemotherapy fatigue and immune status in breast cancer patients, suppressed the expression of Leptin/AMPK signaling pathway-related factor and leukocyte counts, and significantly reduced the rate of mitochondrial DNA mutations in peripheral blood leukocytes.
Conclusion
The Leptin/AMPK signaling pathway may be the key molecular pathway affecting the occurrence of fatigue after chemotherapy in breast cancer patients. Leptin may improve post-chemotherapy fatigue in breast cancer patients by activating AMPK phosphorylation and alleviating mitochondrial functional impairment.
... Research indicates that various genetic and environmental factors contribute to their development and progression [9]. Among these risk factors, some are difficult to modify, while others, such as obesity, are more susceptible to medical and behavioral interventions [10][11][12]. Obesity has long been recognized as a substantial risk factor for the onset and progression of OA, with a heightened body mass index (BMI) notably linked to the occurrence of knee and hip OA [13]. However, the association between obesity and RA is less clear, as some studies suggest a positive relationship, while others find no significant connection [14]. ...
Introduction
The weight-adjusted-waist Index (WWI), an innovative metric for assessing obesity, exhibits superior efficacy in appraising lean muscle and adipose tissue mass relative to both the Body Mass Index (BMI) and Waist Circumference (WC). The objective of this research paper is to investigate the correlation between WWI and the incidence of Rheumatoid Arthritis (RA) and Osteoarthritis (OA).
Methods
In this population-based study, we collected data from adult participants aged 20–80 years using the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2020 to analyze the association between WWI and the occurrence of RA and OA. NHANES, a nationally representative cross-sectional survey, is designed to evaluate the health and nutritional status of the U.S. population. The current research incorporates an extensive, nationally representative sample of U.S. adults, utilizing weighted multivariate linear regression and smoothed curve fitting techniques to examine linear and non-linear relationships. Threshold effects were determined through a two-part linear regression model. Additionally, subgroup analyses and interaction tests were conducted to explore the connection between WWI and the incidence of RA and OA.
Results
Our findings reveal a linear positive correlation between WWI and OA prevalence, indicating that an increase in WWI is linked to a heightened risk of OA. Conversely, a non-linear relationship was observed between WWI and RA prevalence, exhibiting a significant threshold effect with a saturation value of 11.21 cm/√kg. A positive association was detected to the left of the saturation point, while no significant association was present between the two variables to the right of the saturation point, suggesting a complex non-linear relationship between RA prevalence and WWI.
Conclusions
This investigation demonstrates a positive linear association between WWI and OA prevalence, as well as a complex non-linear relationship with RA prevalence in U.S. adults aged 20–80 years.
... Adipokines are either adipocyte specific proteins (e.g., leptin, adiponectin) or commonly produced by many other cells (e.g., TNFα, IL-1, IL-6). The link between many adipokines and OA was widely described by MacDonald et al. [54]. In 2006, Presle et al. described the difference between serum and synovial distribution of adipokines. ...
... Leptin, the adipokine discovered in 1994, has a global proinflammatory effect. Obese people usually present a higher level of inflammation markers including increased activity in synovial fluid [54]. As leptin regulates hunger, the hypothalamic regulation via leptin exposure among obese people remains insufficient. ...
Osteoarthritis (OA) is a common disease among the human population worldwide. OA causes functional impairment, leads to disability and poses serious socioeconomic burden. The rehabilitation offers a function-oriented method to reduce the disability using diverse interventions (kinesiotherapy, physical therapy, occupational therapy, education, and pharmacotherapy). OA as a widespread disease among elderly patients is often treated by rehabilitation specialists and physiotherapists, however the results of rehabilitation are sometimes unsatisfactory. The understanding of molecular mechanisms activated by rehabilitation may enable the development of more effective rehabilitation procedures. Molecular biology methods may prove crucial in rehabilitation as the majority of rehabilitation procedures cannot be estimated in double-blinded placebo-controlled trials commonly used in pharmacotherapy. This article attempts to present and estimate the role of molecular biology in the development of modern rehabilitation. The role of clinicians in adequate molecular biology experimental design is also described.
... In addition to the endocrinologic problems, leptin also affects the disease processes of various musculoskeletal diseases, such as knee osteoarthritis [16]. Leptin has been shown to orchestrate the fibroblastic and inflammatory processes of various human diseases. ...
Shoulder stiffness (SS) is a disease that is fibroblastic and inflammatory in nature. Leptin is an adipokine-mediating the fibroblastic and inflammatory processes of various diseases. Our study tried to investigate the role of leptin in SS pathogenesis. Subacromial bursa from stiff and non-stiff shoulders were obtained for reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunoblotting. Subacromial fluid was obtained for enzyme-linked immunosorbent assay. We showed that the expression level of leptin was lower in the subacromial bursae from the stiff shoulders in RT-PCR analysis (p < 0.001) and immunoblotting (p < 0.001). The concentration of leptin was also lower in the subacromial fluid derived from stiff shoulders. The leptin level in the subacromial fluid was positively associated with the constant score, total range of motion, flexion, abduction, and external rotation. The synovial fibroblasts derived from stiff shoulder-retrieved subacromial bursa were treated by 0, 1, and 3 μM leptin. Under RT-qPCR analysis, leptin was shown to dose-dependently decrease the transcription of IL-6, IL-10, and IL-13, but without impact on IL-1β and IL-4 (p < 0.001, p = 0.001, p = 0.001, p = 0.137, and p = 0.883 by ANOVA test, respectively). These results shed light on the role of leptin in orchestrating the disease processes of SS.
... The first is a biomechanical effect of excessive stress on the joints, which initiates changes in the cartilage and other structures of weight-bearing joints, particularly the knee (23). The second concerns obesity-linked systemic mechanisms, which hinge on the role of fat, particularly central adiposity (abdominal and visceral fat) as a source of inflammatory cytokines and adipokines that influence OA-related processes within the joint (24,25). ...
Objective
To determine whether an apparent association between hand osteoarthritis (OA) and adiposity is explained by the presence of OA at other joint sites.
Methods
Data from the Canadian Longitudinal Study on Aging, first cycle, comprehensive cohort, were used. Respondents age 45–85 years (n = 18,279) were asked separate questions about doctor‐diagnosed OA in the hand, hip, or knee. Multinomial logistic regression was used to investigate the relationship between all combinations of hand, hip, and knee OA and body mass index (BMI) and waist‐to‐height ratio (WHtR).
Results
OA was reported by 34.6% of respondents, 28.0% with OA at >1 joint site. Hand OA was not significantly associated with BMI after accounting for OA at other joint sites, with similar findings for WHtR. All joint site combinations containing the knee were strongly associated with BMI, with odds ratios (ORs) ranging from OR 2.92 (95% confidence interval [95% CI] 2.53–3.37) for knee OA only with obesity class I to OR 9.98 (95% CI 7.12–13.88) for multi‐joint knee, hip, hand OA with obesity class II/III. BMI distributions including knee OA were broader and shifted to higher BMI levels than those for hand or hip OA.
Conclusion
Apparent associations between hand OA and BMI may be explained by concurrent OA at other joint sites. Recognizing that OA is a multi‐joint disease is crucial for studies of the associations of adiposity with OA in a particular joint, especially the hand. The association between knee OA and BMI appears to be distinct from those for OA at other joint sites.
... The population in this study was middle-aged and aging has been associated with a decline in immunity (31) that includes changes in autoantibody levels (32) that could be in uencing the progression of the disease. Obesity has also been shown to contribute to SLE (28, 33) and rheumatoid arthritis (34) -another autoimmune disease -via changes in adipokines, in ammatory cytokines, released from adipose tissue (35,36). Adipose tissue also contains aromatase enzymes and enhances to steroid hormone levels by converting androgens to estrogens (37). ...
Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes.
Aims: The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and Histone Deacetylase 1 (HDAC1) in Iranian patients with SLE.
Methods: This matched case-control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjan rheumatology clinic, in the southeast of Iran. The expression of DNMT and HDAC1 genes was measured through a Real-time PCR assay of blood samples.
Results: DNMT gene expression did not differ significantly between SLE and healthy groups (P=0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P=0.94).
Conclusion: The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes are related to SLE disease is essential and may help to form an accurate diagnosis of the disease.
... 5 Both common forms of arthritis are increased with obesity 6 7 8 , and proinflammatory adipokines have been implicated in both RA and OA. 9 A number of environmental exposures have been documented to be risk factors for development of arthritis. Smoking increases the prevalence, incidence and progression of OA 10 and RA 11 . ...
Rheumatoid arthritis is an autoimmune disease, while osteoarthritis is presumed to be a disease due to wear and tear causing damage to joints. Some environmental exposures, such as smoking, air pollution and possibly persistent organic pollutants, are known to increase the risk of both. We have utilized the National Health and Nutrition Examination Survey (NHANES) data to determine associations between self-reported prevalence of any form of arthritis, rheumatoid and osteoarthritis and various polychlorinated biphenyl (PCB) congeners, several chlorinated pesticides and 2.3,7,8-tetrachloro-dibenzo-dioxin (TCDD). We find that there is a statistically significant association between serum PCB levels of more highly chlorinated PCB congeners and both types of arthritis. The associations are stronger with rheumatoid arthritis than with osteoarthritis, and stronger in women than in men.
