Threading analysis suggests that the obese gene product may be a helical cytokine

Madej, Thomas; Boguski, Mark S.; Bryant, Stephen H.

doi:10.1016/0014-5793(95)00977-h

Cited by 236 publications

(139 citation statements)

References 41 publications

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“…This observation was consistent with a previous structural prediction indicating that the leptin protein would be expected to fold into a cytokine-like structure (30). The closest relatives of OB-R were gp130 (31), the G-CSF receptor (32), and the leukemia inhibitory factor receptor (33).…”

supporting

confidence: 91%

The Leptin Receptor

Tartaglia

1997

Journal of Biological Chemistry

1,217

873

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supporting

confidence: 91%

The Leptin Receptor

Tartaglia

1997

Journal of Biological Chemistry

1,217

873

View full text Add to dashboard Cite

“…First, although the cloning of the Ob gene revealed no significant se quence homology with any other known protein, com putational based research studies predicted that leptin displayed tridimensional characteristics of a four helix bundled cytokine, such as those that activate the JAK STAT pathway (Figure 1) (13). Moreover, the cloning of the OB-R gene reported towards the end of 1995 (12) revealed that leptin receptor shared sequence ho mology with gp130, the signal transducing unit of the IL 6 receptor that signals via the JAK STAT pathway.…”

Section: Molecular Mechanisms Of Leptin and Modulation Of Immune Cellsmentioning

confidence: 99%

Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications

Paz-Filho

Mastronardi

Franco

et al. 2012

Arq Bras Endocrinol Metab

179

148

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SUMMARYLeptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Arq Bras Endocrinol Metab. 2012;56(9):597-607 Keywords Leptin; immunity; inflammation; cytokines SUMÁRIO A leptina, uma adipocina produzida principalmente pelo tecido adiposo branco, tem um papel importante não somente na regulação da ingestão alimentar, mas também no controle da imunidade e da inflamação. Já foi amplamente demonstrado que a ausência de leptina causa deficiências imunológicas em modelos animais e em humanos, levando ao aumento da mortalidade. A leptina também regula a inflamação por meio da ação em seu receptor, amplamente distribuído em diversos tipos de células do sistema imunológico. Os mecanismos moleculares pelos quais a leptina determina suas ações biológicas foram recentemente elucidados, e três cascatas intracelulares são ativadas pela leptina: JAK-STAT, PI3K e ERK 1/2. Essas cascatas são reguladas por proteínas intracelulares, reduzindo as ações da leptina. Nesta revisão, são discutidos os mecanismos moleculares pelos quais a leptina regula a imunidade e a inflamação, associando-os a enfermidades inflamatórias crônicas. Arq Bras Endocrinol Metab. 2012;56(9):597-607 Descritores

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“…The primary amino acid sequence of leptin indicated that it could belong to the long-chain helical cytokine family, 36,42 with members such as IL-2 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune response.…”

Section: Leptin Inflammation and Immune Responsementioning

confidence: 99%

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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Threading analysis suggests that the obese gene product may be a helical cytokine

Cited by 236 publications

References 41 publications

The Leptin Receptor

The Leptin Receptor

Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications

Leptin in immuno-rheumatological diseases

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