High expression of leptin by human bone marrow adipocytes in primary culture

Laharrague, Patrick; Larrouy, Dominique; Fontanilles, A.M.; Truel, Nathalie; Campfield, A.; Tenenbaum, Renata; Galitzky, Jean; Corberand, J; Pénicaud, Luc; Casteilla, Louis

doi:10.1096/fasebj.12.9.747

Cited by 175 publications

(111 citation statements)

References 38 publications

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“…Conversely, it is known that adipocytes participate in the microenvironment of the bone marrow and that these adipocytes are a secondary source of leptin production (20). Thomas et al (14) recently demonstrated a direct osteogenic effect of leptin on a human marrow stromal cell line with the capability to differentiate to either osteoblasts or adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Plasma leptin concentrations in postmenopausal women with osteoporosis

Odabaşı¹,

Özata

Turan³

et al. 2000

European Journal of Endocrinology

100

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Background: The obese are usually protected against osteoporosis and have increased bone mineral density and plasma leptin concentrations. A recent in vitro study demonstrated that leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts, suggesting an influence of leptin on bone mass. However, little is known about the relationship between plasma leptin and bone mass in postmenopausal women with osteoporosis. Objective: To investigate plasma leptin concentrations in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in determining bone mass. Methods: Fifty postmenopausal women with osteoporosis (ages 61.18 Ϯ 6.51 years; body mass index (BMI) 28.91 Ϯ 3.44 kg/m

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Section: Discussionmentioning

confidence: 99%

Plasma leptin concentrations in postmenopausal women with osteoporosis

Odabaşı¹,

Özata

Turan³

et al. 2000

European Journal of Endocrinology

100

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“…Limit of detection for the assay was 0.2 ngaml. 14 Pearson's correlation coef®cient r was used to evaluate associations between BM and plasma leptin. Student's t-test was used for statistical signi®cance.…”

Section: Leptin Determinationsmentioning

confidence: 99%

High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects

et al. 2000

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OBJECTIVE AND DESIGN: As well as its involvement in control of adipose mass and body energy balance, several reports suggest a link between leptin and hemopoiesis. To test its putative role in human hemopoiesis, we developed a homologous system, ie recombinant human leptin treatment of puri®ed CD34 progenitors from adult human bone marrow. RESULTS: Leptin (50 ± 100 ngaml) signi®cantly stimulated the appearance of granulocyte-macrophage colonies in the presence or absence of erythropoietin. The concentration of leptin required for this effect was rather high but within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocytosis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; (ii) leptin and leukocyte count were correlated only in obese subjects. Paracrine effects of locally released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochemistry revealing the close association of CD34 cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these cells. CONCLUSION: These results indicate that leptin acts on human multilineage CD34 cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progenitors.

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“…1 Adipocytes are abundant in the bone marrow (BM) microenvironment and might be responsible for the high concentration of leptin in BM. 2 The leptin receptor (OB-R) has recently been detected on human hematopoietic progenitor cells expressing the CD34 antigen, and leptin was reported to induce proliferation and differentiation in these cells. 3,4 Multiple isoforms of OB-R have been identified, including a long isoform and several isoforms with short cytoplasmic domains.…”

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confidence: 99%

PML-RARα is associated with leptin-receptor induction: the role of mesenchymal stem cell–derived adipocytes in APL cell survival

Tabe

Konopleva²,

Munsell³

et al. 2004

Blood

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Leptin is secreted by bone marrow (BM) adipocytes and stromal cells and was shown to stimulate myeloid proliferation. We here report that primary acute promyelocytic leukemia (APL) cells express high levels of the leptin-receptor (OB-R) long isoform. In cells with regulated promyelocytic leukemia-retinoic acid receptor (PML-RAR␣) expression, inducing PML-RAR␣ was found to increase OB-R levels. We then investigated the effects of leptin produced by BM adipocytes on APL cells using a coculture system with mesenchymal stem cell (MSC)-derived adipocytes. In PML-RAR␣-expressing cells, all-trans retinoic acid (ATRA)-and doxorubicininduced apoptosis were significantly reduced by coculture with adipocytedifferentiated MSCs. This antiapoptotic effect required direct cell-to-cell interactions, was associated with phosphorylation of signal transducer and activator of transcription-3 (STAT3) and mitogenactivated protein kinase (MAPK), and was reduced by blocking OB-R. This report provides a mechanistic basis for the BM adipocyte-leukemia cell interaction and suggests that OB-R receptor blockade may have therapeutic use in APL. IntroductionLeptin is a 16-kDa protein produced by adipocytes and was originally identified as a cytokine that regulates fat metabolism. 1 Adipocytes are abundant in the bone marrow (BM) microenvironment and might be responsible for the high concentration of leptin in BM. 2 The leptin receptor (OB-R) has recently been detected on human hematopoietic progenitor cells expressing the CD34 antigen, and leptin was reported to induce proliferation and differentiation in these cells. 3,4 Multiple isoforms of OB-R have been identified, including a long isoform and several isoforms with short cytoplasmic domains. 5,6 Although all isoforms share an identical extracellular ligand-binding domain with homology to the class I cytokine receptor family, they differ at the C-terminus. 6 Only the long OB-R isoform, which has the longest (303 amino acids) cytoplasmic domain and encodes all protein motifs, has the signaling capabilities of interleukin-6 (IL-6)-type cytokine receptors and can activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signal transduction pathway. [7][8][9] We have reported that leptin induces the proliferation and enhances the survival of primary leukemic cells from patients with acute myeloid leukemia (AML). 10 We have further demonstrated the presence of leptin receptors (OB-Rs) on primary AML cells, with the highest expression of OB-R long isoform on acute promyelocytic leukemia (APL) cells, which was absent on normal promyelocytes. 10 Given that APL is associated with increased body mass index (BMI) 11 and leptin serum levels correlate with body fat percentage, 12,13 leptin may play a role in the pathophysiology of APL. Alternatively, leptin secretion by BM adipocytes in the vicinity of leukemic cells could play a major role in the proliferation and survival of APL cells through paracrine interactions in the marrow microenvironment. The aims of this study we...

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High expression of leptin by human bone marrow adipocytes in primary culture

Cited by 175 publications

References 38 publications

Plasma leptin concentrations in postmenopausal women with osteoporosis

Plasma leptin concentrations in postmenopausal women with osteoporosis

High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects

PML-RARα is associated with leptin-receptor induction: the role of mesenchymal stem cell–derived adipocytes in APL cell survival

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