Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio.
Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio.
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DOI：
10.1371/journal.pone.0145992
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Karmazyn M
中科院分区：
文献类型：
--
作者：
Bairwa SC;Rajapurohitam V;Gan XT;Mangat R;Proctor SD;Karmazyn M
已知白色脂肪细胞通过分泌过多的生物活性脂肪因子而起内分泌器官的作用，所述脂肪因子可以调节心脏功能，包括肥大的发展。我们确定是否脂肪组织条件培养基（ATCM）产生的正常大鼠附睾区域可以影响培养的大鼠心室肌细胞的肥大反应内皮素-1（ET-1）管理。在不存在或存在增加的ATCM浓度的情况下，用ET-1（10 nM）处理肌细胞24小时。ATCM以浓度依赖性方式抑制对ET-1的肥大反应，瘦素受体拮抗剂增强这种作用，脂联素AdipoR 1受体抗体减弱这种作用。从肾周脂肪组织产生的ATCM也观察到抗肥大作用。然而，这种效果是不存在的ATCM脂肪组织收获肥胖的JCR：LA-cp大鼠。对正常和肥胖大鼠ATCM中脂肪因子含量的详细分析显示，大多数测定的产物没有差异，尽管观察到瘦素浓度显著增加伴随着脂联素水平降低，导致JCR：LA-cp ATCM中瘦素与脂联素比率增加11倍。ATCM的抗肥大作用与AMP活化蛋白激酶（AMPK）磷酸化增加有关，AdipoR 1抗体可消除这种作用。此外，ATCM的抗肥大作用被AMPK激活剂模拟。在ATCM存在或不存在的情况下，ET-1加入后24小时对丝裂原活化蛋白激酶（MAPK）活性均无影响。我们的研究表明，来自健康受试者的脂肪组织通过脂联素依赖性途径发挥抗肥大作用，该途径在肥胖症中受损，最有可能是由于脂肪细胞重塑导致瘦素增强和脂联素水平降低。
White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin–dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.