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前列腺雄激素抑制信使 1 作为调节小鼠脂肪细胞分化的因子。

Prostatic androgen-repressed message-1 as a regulator of adipocyte differentiation in the mouse.

机构信息

Lab of Animal Physiology, Graduate School of Agriculture Science, Tohoku University, Sendai, Japan.

出版信息

Tohoku J Exp Med. 2009 Dec;219(4):311-7. doi: 10.1620/tjem.219.311.

Abstract

Adipocyte differentiation is an important aspect in energy homeostasis. Although the regulation of adipocyte differentiation is relatively well understood, the underlying molecular mechanism remains unclear. In this study, subcutaneous and epididymal adipose tissues were used to study the differential expression of associated genes. We found that the expression level of mouse homologue of rat prostatic androgen-repressed message-1 (mPARM-1) gene was higher in subcutaneous, perirenal and mesenteric adipose tissues than in epididymal adipose tissue. In mouse subcutaneous, perirenal, and mesenteric adipose tissues, the expression level of this gene was higher in adipocytes than in non-adipocyte cells, i.e. stromal-vascular cells. Furthermore, mPARM-1 mRNA expression was up-regulated in subcutaneous, mesenteric, and epididymal adipose tissues of mice fed a high-fat diet compared to those fed a normal-fat diet. Expression level of mPARM-1 mRNA increased in the early stage of the chemically induced adipocyte differentiation, preceding the increase in peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma2) mRNA. Tumor necrosis factor-alpha (TNF-alpha), an inhibitor of adipocyte differentiation, reduced the expression of mPARM-1 mRNA in differentiated 3T3-L1 cells and subsequently down-regulated the expression of adipogenic genes, including PPAR-gamma2, leptin and adipogenin. Moreover, knockdown of mPARM-1 expression with siRNA reduced lipid accumulation and the expression levels of PPAR-gamma2 and adipocyte protein 2 mRNAs, which suggest that the degree of adipocyte differentiation of 3T3-L1 cells has been reduced. These results indicate that mPARM-1 might be involved in the regulation of fat accumulation and adipocyte differentiation.

摘要

脂肪细胞分化是能量平衡的一个重要方面。虽然脂肪细胞分化的调节机制已被广泛研究,但其中的分子机制仍不清楚。本研究采用皮下和附睾脂肪组织,研究相关基因的差异表达。我们发现,鼠同源大鼠前列腺雄激素抑制信使-1(mPARM-1)基因在皮下、肾周和肠系膜脂肪组织中的表达水平高于附睾脂肪组织。在小鼠的皮下、肾周和肠系膜脂肪组织中,该基因在脂肪细胞中的表达水平高于非脂肪细胞,即基质血管细胞。此外,高脂肪饮食喂养的小鼠的皮下、肠系膜和附睾脂肪组织中 mPARM-1mRNA 的表达水平高于正常脂肪饮食喂养的小鼠。mPARM-1mRNA 的表达水平在化学诱导的脂肪细胞分化早期上调,早于过氧化物酶体增殖物激活受体-γ2(PPAR-γ2)mRNA 的增加。肿瘤坏死因子-α(TNF-α),脂肪细胞分化的抑制剂,降低了分化的 3T3-L1 细胞中 mPARM-1mRNA 的表达,并随后下调了脂肪生成基因的表达,包括 PPAR-γ2、瘦素和脂肪生成素。此外,用 siRNA 敲低 mPARM-1 的表达降低了 3T3-L1 细胞的脂质积累和 PPAR-γ2 和脂肪细胞蛋白 2 mRNA 的表达水平,这表明 3T3-L1 细胞的脂肪细胞分化程度降低。这些结果表明,mPARM-1 可能参与脂肪积累和脂肪细胞分化的调节。

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