A role for leptin and its cognate receptor in hematopoiesis

Bennett, Brian D.; Solar, Gregg P.; Yuan, Jean Q.; Mathias, Joanne; Thomas, George; Matthews, William

doi:10.1016/s0960-9822(02)70684-2

Cited by 442 publications

(307 citation statements)

References 41 publications

(59 reference statements)

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“…Previous studies on db/db mice established a role for leptin in modulating lymphocyte development and found no correlation between blood glucose levels and the number of lymphocytes in lymphoid organs, suggesting that the lymphocyte deficit in db/db mice is not a result of the ensuing diabetic state [8]. However, the presence of hyperglycemia and deregulated cortisol levels in diabetic animals may affect the development of immune cells as well as immune responses.…”

Section: Discussionmentioning

confidence: 96%

“…The structure of leptin has high similarity to members of the long-chain helical cytokines such as IL-6, IL-11, IL-12, G-CSF, leukemia inhibitory factor and oncostatin [4,5]. Several studies have revealed an important role for leptin in regulating lymphopoiesis and hematopoiesis [1,2,[6][7][8]. For example, leptin has been shown to stimulate proliferation and increase the production of a variety of cytokines in rodent T cells and monocytes/macrophages [2,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…For example, leptin has been shown to stimulate proliferation and increase the production of a variety of cytokines in rodent T cells and monocytes/macrophages [2,[9][10][11]. In relation to the important function of leptin in immune responses, leptin receptor (Ob-R) expression has been found not only in the central nervous system but also in peripheral lymphoid tissues and hematopoietic stem cells [2,8,12]. Encoded by the diabetes (db) gene, the Ob-R is a member of the class I cytokine receptors, which have the signaling capability of IL-6-type cytokine receptors [4].…”

Section: Introductionmentioning

confidence: 99%

“…Ob-R mRNA gives rise to six different forms of the receptor by alternative splicing, but only the long isoform (Ob-Rb) has been recognized to be of importance in leptin-mediated signaling [1]. Early studies on db/db mice, in which the Ob-Rb that transduces signals through leptin binding is truncated, revealed that B and T cell development and maturation are severely affected, with reduced numbers of lymphocytes in the peripheral lymphoid organs [8].…”

Section: Introductionmentioning

confidence: 99%

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Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and IjB-a. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation.See accompanying commentary: http://dx

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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“…9,4,33,34 Although it is highly expressed in the brain, the functional long isoform of the leptin receptor OB-Rb is expressed in both human and murine hematopoietic stem cells and in human B-cell progenitors. 18,35 The capacity of bone marrow stromal cells to express leptin provides strong evidence for leptin in development of hematopoietic stem cells. Modulation of the immune system by leptin is exerted at the development, proliferation, antiapoptotic, maturation and activation levels.…”

Section: Introductionmentioning

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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