Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases

Gómez, Rodolfo; Lago, Francisca; Gómez-Reino, Juan J.; Diéguez, Carlos; Gualillo, Oreste

doi:10.1677/jme-08-0131

Cited by 82 publications

(56 citation statements)

References 60 publications

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“…Indeed, after binding to its receptors or hyphothalamic neurons, leptin regulates osteoblasts, bone formation and osteoclast differentiation. 76 Nitric oxide has well-documented proinflammatory effects on joint cartilage, triggering the loss of the chondrocyte phenotype, chondrocyte apoptosis and the activation of metalloproteinases. In cultured chondrocytes, nitric oxide synthase is activated by leptin plus interferon (INF)-c and by the combination of leptin plus IL-1 (Figure 4).…”

Section: Leptin and Autoimmunity M Vadacca Et Al 207mentioning

confidence: 99%

“…In addition, another way to target leptin activity might consist of blocking the leptin receptor with humanized monoclonal antibodies or mutant leptin analogues that are able to bind to the receptor without activating it. 76 In addition, recombinant methionyl human leptin replacement could prove to be a new and potentially useful therapy to be added to our therapeutic armamentarium for the treatment of disease states of absolute or relative leptin deficiency and to restore immune function.…”

Section: Leptin Connective Tissue Diseases and Organ-specific Autoimmentioning

confidence: 99%

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Leptin in immuno-rheumatological diseases

et al. 2011

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Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions. One of these functions is the relationship between nutritional status and immune competence. It structurally resembles proinflammatory cytokines, such as IL-6 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. The role of leptin in regulating immune responses has been assessed in vitro as well as in clinical studies. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders, such as autoimmune diseases, are associated with the increased secretion of leptin and the production of proinflammatory pathogenic cytokines. In this paper, we review the most recent advances of the role of leptin in immune-rheumatological diseases, and we discuss whether strategies aimed at modifying leptin levels could represent innovative and therapeutic tools for autoimmune disorders. Keywords: adipokines; autoimmune diseases; leptin; rheumatic diseases INTRODUCTIONThe existence of a factor secreted by white adipose tissue (WAT), which acts to control feeding, weight and WAT mass, was first proposed by Kennedy 1 and is supported by monogenic mutations resulting in obesity. [2][3][4] WAT is composed of adipocytes filled mainly with triacylglycerol and embedded in loose connective tissue containing adipocyte precursors, fibroblasts, immune and other cells. Obesity, the condition that originally motivated the research on WAT, is characterized by low-grade systemic inflammation. It is thought that excess WAT can contribute to the maintenance of obesity through inflammation-inducing lipotoxicity by secreting factors that stimulate the synthesis of inflammatory agents in other organs and by secreting inflammatory agents itself. 5 The current view of WAT states that it is an active contributor to body homeostasis by sending out and responding to signals that modulate appetite, energy expenditure, insulin sensitivity, the endocrine and reproductive systems, bone metabolism, inflammation and immunity. 6 Several findings have converged to indicate that adipocytes share certain properties with immune cells, such as complement activation 7 and proinflammatory cytokine production. 8 Fat cell precursors also share features with macrophages. Numerous genes that code for transcription factors, cytokines, inflammatory signaling molecules, and fatty acid transporters are essential for adipocyte biology and are also expressed and functional in macrophages. 9 Adipose tissue secrets a variety of factors: the term 'adipokine' is generally given to any protein that can be synthesized and secreted by adipocytes. Among these factors, only leptin and adiponectin (and possibly resistin, adipsi...

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Section: Leptin and Autoimmunity M Vadacca Et Al 207mentioning

confidence: 99%

Section: Leptin Connective Tissue Diseases and Organ-specific Autoimmentioning

confidence: 99%

Leptin in immuno-rheumatological diseases

et al. 2011

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“…Some adipokines thus play a significant role in the pathogenesis of immune-mediated disorders like RA, spondyloarthritis, systemic lupus erythematosus, and probably other autoimmune rheumatic diseases as well as degenerative rheumatic disorders such as osteoarthritis [23]. With respect to the latter, it can be suggested that the association between obesity and osteoarthritis may well be triggered by adipokine dysregulation.…”

Section: Discussionmentioning

confidence: 99%

Adipokines: role in local and systemic inflammation of rheumatic diseases

Šenolt

2016

Expert Review of Clinical Immunology

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“…There is some evidence that adiponectin in skeletal joints may have proinflammatory effects and may be involved in cartilage degradation [4,27].…”

Section: Discussionmentioning

confidence: 99%

Effects of Spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis

et al. 2010

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The aim of the present study was to assess whether spa therapy modified plasma levels of leptin and adiponectin in thirty patients with knee OA treated with a cycle of a combination of daily locally-applied mud packs and bicarbonate-sulphate mineral bath water. Leptin and adiponectin plasma levels were assessed at baseline and after two weeks, upon completion of the spa treatment period. The concentrations of leptin and adiponectin were measured by ELISA.At basal time, plasma leptin levels were significantly correlated with body mass index (BMI) and gender, but no significant correlation was found with patient age, duration of disease, radiographic severity of knee OA, VAS score or Lequesne index.There was no correlation between plasma adiponectin level and BMI, gender and age, duration of the disease, radiographic severity of knee OA, and VAS score. A significant correlation of plasma adiponectin levels was found only with the Lequesne index.At the end of the mud-bath therapy cycle, serum leptin levels showed a slight but not significant increase, while a significant decrease (p<0.05) of serum adiponectin levels was found. However, leptin and adiponectin concentrations after treatment were not correlated with other clinical parameters.In conclusion, our data show that spa therapy can modify plasma levels of the adipocytokines leptin and adiponectin, important mediators of cartilage metabolism. Whether this effect may play a potential role in OA needs further investigations.

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Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases

Cited by 82 publications

References 60 publications

Leptin in immuno-rheumatological diseases

Leptin in immuno-rheumatological diseases

Adipokines: role in local and systemic inflammation of rheumatic diseases

Effects of Spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis

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