Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-γ
Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-γ
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DOI：
10.2337/diabetes.53.5.1243
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发表时间：
2004-05-01
期刊：
影响因子：
7.7
通讯作者：
Nebbl, HI
中科院分区：
文献类型：
--
作者：
Dalen, KT;Schoonjans, K;Nebbl, HI
在过氧化物酶体增殖物激活受体-γ（PPAR-gamma）靶基因的系统搜索中，我们确定了S3-12和perilipin作为新的直接PPAR-gamma靶基因。与adipophilin和47 kDa的尾部相互作用蛋白一起，这些基因是具有不同表达模式但在脂肪组织中重叠表达的脂滴相关蛋白。S3-12和perilipin的表达与脂肪细胞中PPAR-gamma的表达和活化密切相关，启动子表征显示S3-12和perilipin启动子分别含有三个和一个进化上保守的PPAR应答元件。我们进一步证明，S3-12和perilipin的表达减少肥胖与瘦Zucker大鼠相比，而adipophilin的表达增加。其他人已经表明，围脂蛋白是脂肪组织内储存的甘油三酯的脂解的激素调节中的重要因子。因此，通过PPAR-gamma对围脂蛋白和S3-12的直接调节可能是PPAR-gamma激活剂长期治疗的体内效应的重要介质：胰岛素敏化、脂肪组织中的脂肪酸捕获、减少的基础脂肪脂解和体重增加。
In a systematic search for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) target genes, we identified S3-12 and perilipin as novel direct PPAR-gamma target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet-associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-gamma in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-gamma therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-gamma activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain.