Adiponectin translation is increased by the PPARγ agonists pioglitazone and ω-3 fatty acids
Adiponectin translation is increased by the PPARγ agonists pioglitazone and ω-3 fatty acids
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DOI：
10.1152/ajpendo.90892.2008
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发表时间：
2009-03-01
影响因子：
5.1
通讯作者：
Ranganathan, Gouri
中科院分区：
文献类型：
--
作者：
Banga, Anannya;Unal, Resat;Ranganathan, Gouri
邦加A，Unal R，Tripathi P，Pokrovskaya I，Owens RJ，克恩PA，Ranganathan G.脂联素翻译增加的过氧化物酶体增殖物激活受体γ激动剂吡格列酮和ω-3脂肪酸。Am J Physiol Endocrinol Metab 296：E480-E489，2009.首次发表于2008年12月16日; doi：10.1152/ajpendo.90892.2008。脂联素是一种由脂肪细胞分泌的分子量为30 kDa的分泌性蛋白质，主要由低分子量、中分子量和高分子量的同源寡聚体组成。广泛用于治疗II型糖尿病的PPAR γ配体噻唑烷二酮类可增加脂联素水平。PPARgamma也有几种推定的配体，包括脂肪酸衍生物。用吡格列酮、二十二碳六烯酸（DHA）或二十碳五烯酸（EPA）过夜处理大鼠脂肪细胞，引发HMW脂联素合成和分泌增加两倍，这种增加可通过加入PPAR γ抑制剂GW-9662阻断。使用2，2 '-联吡啶抑制糖基化降低了吡格列酮、EPA和DHA合成高分子量脂联素，但由于翻译增加，三聚体脂联素的分泌增加。尽管吡格列酮、DHA和EPA使脂联素合成增加60%以上，但总蛋白合成没有增加，脂联素mRNA表达也没有相应变化，表明翻译上调。我们研究了吡格列酮或DHA处理的脂肪细胞胞质提取物中反式因子的可能性。脂联素mRNA的体外翻译被对照脂肪细胞的S-100组分抑制，并被吡格列酮或DHA处理的脂肪细胞的S-100提取物增加。与这一观察结果一致，吡格列酮和DHA治疗增加了脂联素mRNA与较重的多核糖体组分的关联。总之，这些数据表明，吡格列酮和鱼油DHA或EPA是脂肪细胞中脂联素表达的PPAR γ激动剂，脂联素刺激的主要模式是通过增加翻译。
Banga A, Unal R, Tripathi P, Pokrovskaya I, Owens RJ, Kern PA, Ranganathan G. Adiponectin translation is increased by the PPAR gamma agonists pioglitazone and omega-3 fatty acids. Am J Physiol Endocrinol Metab 296: E480-E489, 2009. First published December 16, 2008; doi:10.1152/ajpendo.90892.2008.-Adiponectin, made exclusively by adipocytes, is a 30-kDa secretory protein assembled posttranslationally into low-molecular weight, middle-molecular weight, and high-molecular weight homo-oligomers. PPAR gamma ligand thiozolidinediones, which are widely used in the treatment of type II diabetes, increase adiponectin levels. PPAR gamma also has several putative ligands that include fatty acid derivatives. Overnight treatment of rat adipocytes with pioglitazone, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) triggered a twofold increase in the synthesis and secretion of HMW adiponectin, and this increase was blocked by the addition of PPAR gamma inhibitor GW-9662. Inhibition of glycosylation using 2,2'-dipyridyl decreased the synthesis of high-molecular weight adiponectin by pioglitazone, EPA, and DHA, but there was increased secretion of trimeric adiponectin resulting from increased translation. Although pioglitazone, DHA, and EPA increased adiponectin synthesis by more than 60%, there was no increase in total protein synthesis and no corresponding change in adiponectin mRNA expression, indicating the upregulation of translation. We examined the possibility of transacting factors in the cytoplasmic extracts from adipocytes treated with pioglitazone or DHA. In vitro translation of adiponectin mRNA was inhibited by S-100 fraction of control adipocytes and increased by S-100 extracts from adipocytes treated with pioglitazone or DHA. Consistent with this observation, both pioglitazone and DHA treatments increased the association of adiponectin mRNA with the heavier polysome fractions. Together, these data suggest that pioglitazone and the fish oils DHA or EPA are PPAR gamma agonists in adipocytes with regard to adiponectin expression, and the predominant mode of adiponectin stimulation is via an increase in translation.