Human Leptin Signaling in Human Peripheral Blood Mononuclear Cells: Activation of the JAK-STAT Pathway

Sánchez‐Margalet, Víctor; Martín-Romero, Consuelo

doi:10.1006/cimm.2001.1815

Cited by 122 publications

(106 citation statements)

References 48 publications

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“…In addition, leptin is a trophic and mitogenic factor for trophoblastic cell line by virtue of inhibiting apoptosis and promoting proliferation [92]. In this context, it has reported that leptin promotes growth, proliferation and cell survival of trophoblastic cells [89] by activating JAK-STAT, MAPK, and PI3K signaling pathways [93][94][95][96]. More specifically, leptin enhances cell proliferation in a dose-and time-dependent fashion, displaced the cells towards a G2/M phase as well as upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins [92].…”

Section: Role Of Leptin In Placentationmentioning

confidence: 99%

Role of leptin in female reproduction

Pérez-Pérez

Sánchez-Jiménez

Maymó

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

127

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Abstract:Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

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Section: Role Of Leptin In Placentationmentioning

confidence: 99%

Role of leptin in female reproduction

Pérez-Pérez

Sánchez-Jiménez

Maymó

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

127

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“…A number of studies in human PBMCs have shown that, in addition to the JAK-2-STAT-3 pathway, which is an important pathway mediating leptin's effect on immune cells, other pathways are also involved. The MAPK, the insulin receptor substrate 1, and the phosphatidylinositol 3Ј-kinase (PI3ЈK) 4 pathways (20) are also important pathways that mediate leptin's action on immune T cells (21). Moreover, in PBMCs the MAPK pathway seems to mediate antiapoptotic effects (22), whereas the PI3ЈK pathway may be important in regulating glucose uptake (23).…”

Section: Leptin and Leptin Signaling In Immune Cellsmentioning

confidence: 99%

Leptin in Immunology

Matarese

Moschos

Mantzoros

2005

The Journal of Immunology

516

426

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Leptin is an adipokine which conveys information on energy availability. In humans, leptin influences energy homeostasis and regulates neuroendocrine function primarily in states of energy deficiency. As a cytokine, leptin also affects thymic homeostasis and, similar to other proinflammatory cytokines, leptin promotes Th1 cell differentiation and cytokine production. We review herein recent advances on the role of leptin in the pathophysiology of immune responses.

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“…43,44 OB-Rb has been shown to have the signaling capabilities of IL-6-type cytokine receptors, activating janus kinases and signal transducers and activators of transcription (STAT), phosphatidylinositol 3-kinase and the mitogen-activated protein kinase (MAPK) signaling pathways. 36,41,45 Like other cytokine receptor family members, OB-Rb is internalized upon ligand binding via …”

Section: Leptin Inflammation and Immune Responsementioning

confidence: 99%

“…18,48 Among the various STAT proteins activated by OB-Rb, STAT3 has been shown to mediate the leptin signal in activated macrophages and in promoting the survival and activation of lymphocytes and peripheral blood mononuclear cells (PBMCs). 18,45,49,50 In NK cells, leptin is involved in all processes of cell development, differentiation, proliferation, activation and cytotoxicity, and this effect is mediated by STAT3 activation. 51 Based on the complex activation network of the STAT proteins, further analyses of their regulation by leptin signaling in immune cells will merit a better understanding of leptin-mediated immune modulation.…”

Section: Leptin and Autoimmunity M Vadacca Et Al 204mentioning

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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Human Leptin Signaling in Human Peripheral Blood Mononuclear Cells: Activation of the JAK-STAT Pathway

Cited by 122 publications

References 48 publications

Role of leptin in female reproduction

Role of leptin in female reproduction

Leptin in Immunology

Leptin in immuno-rheumatological diseases

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