The weight of leptin in immunity

Cava, Antonio La; Matarese, Giuseppe

doi:10.1038/nri1350

Cited by 792 publications

(707 citation statements)

References 88 publications

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“…25 In macrophages, leptin also upregulates the secretion of proinflammatory cytokines, such as TNF-a, IL-6 and IL-12.…”

Section: Leptin and Autoimmunity M Vadacca Et Al 204mentioning

confidence: 99%

“…23,24 Moreover, leptin levels are reduced during starvation and malnutrition. 25 Leptin expression in adipocytes is induced by insulin, melanyl-CoA, adenosine triphosphate, glucosamine and short-chain fatty acids, but it is inhibited by cyclic adenosine 5'-monophosphate and long-chain fatty acid. 18,26 Furthermore, the expression of leptin can be directly upregulated by sex hormones and is inhibited by testosterone and increased by ovarian sex steroids.…”

Section: Introductionmentioning

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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“…25 In macrophages, leptin also upregulates the secretion of proinflammatory cytokines, such as TNF-a, IL-6 and IL-12.…”

Section: Leptin and Autoimmunity M Vadacca Et Al 204mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Leptin in immuno-rheumatological diseases

et al. 2011

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“…Leptin. Leptin is a 16-kDa protein synthesized by adipocytes that was initially recognized for its role in the regulation of food intake and energy balance, but which has more recently been recognized to also influence inflammatory and immune processes (73). Macrophage LT synthesis was recently found to be reduced in leptin-deficient mice, and this defect was associated with impaired innate immune responses following intrapulmonary challenge with K. pneumoniae (74); the addition of exogenous leptin in vitro restored cellular LT synthetic capacity and the relevant enzymatic mechanisms have recently been identified (75).…”

Section: Modulation Of Lt Synthesis By Other Mediators Of Innate Immumentioning

confidence: 99%

Leukotrienes: Underappreciated Mediators of Innate Immune Responses

Peters‐Golden¹,

Canetti²,

Mancuso

et al. 2005

The Journal of Immunology

275

244

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Leukotrienes are bronchoconstrictor and vasoactive lipid mediators that are targets in the treatment of asthma. Although they are increasingly recognized to exert broad proinflammatory effects, their role in innate immune responses is less well appreciated. These molecules are indeed synthesized by resident and recruited leukocytes during infection. Acting via cell surface G protein-coupled receptors and subsequent intracellular signaling events, they enhance leukocyte accumulation, phagocyte capacity for microbial ingestion and killing, and generation of other proinflammatory mediators. Interestingly, a variety of acquired states of immunodeficiency, such as HIV infection and malnutrition, are characterized by a relative deficiency of leukotriene synthesis. The data reviewed herein point to leukotrienes as underappreciated yet highly relevant mediators of innate immunity.

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“…The existence of a correlation between serum resistin levels and insulin, insulin resistance and blood glucose levels supports this idea [25] . The role of leptin in modulating the immune response and inflammation has become increasingly evident and has been reviewed recently [26,27] . Complex interactions among the nervous, endocrine and immune systems affect the leptin loop and the potential role of these mediators in cancer-related cachexiaanorexia syndrome [8,11,12] .…”

Section: Resistin Ghrelin Leptin Adiponectin Igf-ⅰmentioning

confidence: 99%

Adipokines and ghrelin in gastric cancer cachexia

Kerem

Ferahköşe²,

Yılmaz³

et al. 2008

WJG

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AIM:To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia. METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-Ⅰ), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancerinduced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated. RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P < 0.05). Ghrelin, resistin, leptin, adiponectin and IGF-Ⅰ, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-Ⅰ (P < 0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted. CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-Ⅰ play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

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The weight of leptin in immunity

Cited by 792 publications

References 88 publications

Leptin in immuno-rheumatological diseases

Leptin in immuno-rheumatological diseases

Leukotrienes: Underappreciated Mediators of Innate Immune Responses

Adipokines and ghrelin in gastric cancer cachexia

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