Proadipogenic effect of leptin on rat preadipocytes in vitro:: activation of MAPK and STAT3 signaling pathways

Proadipogenic effect of leptin on rat preadipocytes in vitro:: activation of MAPK and STAT3 signaling pathways
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DOI:
10.1152/ajpcell.00331.2001
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发表时间:
2002-04-01
影响因子:
5.5
通讯作者:
Giudicelli, Y
Giudicelli, Y
中科院分区:
生物学2区
文献类型:
--
作者:
Machinal-Quélin, F;Dieudonné, MN;Giudicelli, Y

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由于瘦素最近已被证明通过不同的途径诱导不同类型的细胞的增殖和/或分化,本研究的目的是调查,在体外,瘦素对大鼠前脂肪细胞脂肪形成的影响。这项研究的先决条件是确定瘦素受体(Ob-Ra和Ob-Rb)的前脂肪细胞从股骨皮下脂肪。我们观察到Ob-Ra和Ob-Rb的表达在脂肪形成过程中增加。此外,瘦素诱导融合和分化的前脂肪细胞中的p42/p44丝裂原活化蛋白激酶磷酸化亚型的增加和仅在融合的前脂肪细胞中的STAT 3磷酸化的增加。此外,暴露于瘦素促进激活蛋白-1复合物的DNA结合活性在融合的前脂肪细胞。最后,暴露的原代培养的前脂肪细胞从皮下区域瘦素(10 nM)导致增加的增殖([H-3]胸苷掺入和细胞计数)和分化(甘油-3-磷酸脱氢酶活性和mRNA水平的脂蛋白脂肪酶,过氧化物酶体增殖物激活受体-γ 2,和c-fos)。总之,这些结果表明,至少在体外,瘦素通过其功能性受体在皮下前脂肪细胞中发挥促脂肪形成作用。
Because leptin has recently been shown to induce proliferation and/or differentiation of different cell types through different pathways, the aim of the present study was to investigate, in vitro, the influence of leptin on adipogenesis in rat preadipocytes. A prerequisite to this study was to identify leptin receptors (Ob-Ra and Ob-Rb) in preadipocytes from femoral subcutaneous fat. We observed that expressions of Ob-Ra and Ob-Rb increase during adipogenesis. Furthermore, leptin induces an increase of p42/p44 mitogen-activated protein kinase phosphorylated isoforms in both confluent and differentiated preadipocytes and of STAT3 phosphorylation only in confluent preadipocytes. Moreover, exposure to leptin promoted activator protein-1 complex DNA binding activity in confluent preadipocytes. Finally, exposure of primary cultured preadipocytes from the subcutaneous area to leptin (10 nM) resulted in an increased proliferation ([H-3] thymidine incorporation and cell counting) and differentiation (glycerol-3-phosphate dehydrogenase activity and mRNA levels of lipoprotein lipase, peroxisome proliferator-activated receptor-gamma2, and c-fos). Altogether, these results indicate that, in vitro at least, leptin through its functional receptors exerts a proadipogenic action in subcutaneous preadipocytes.