SPOCK1 induces adipose tissue maturation: New insights into the function of SPOCK1 in metabolism

SPOCK1 induces adipose tissue maturation: New insights into the function of SPOCK1 in metabolism
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DOI:
10.1016/j.bbrc.2020.09.129
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发表时间:
2020-12-17
影响因子:
3.1
通讯作者:
Nishimura, Fusanori
Nishimura, Fusanori
中科院分区:
生物学4区
文献类型:
--
作者:
Alshargabi, Rehab;Shinjo, Takanori;Nishimura, Fusanori

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SPOCK1是一种钙结合的基质细胞蛋白聚糖,已在几种癌细胞中得到广泛研究。此前,我们构建过表达SPOCK1的小鼠细胞系(SPOCK1 - tg小鼠),发现SPOCK1可能在药物性牙龈过度生长中发挥重要作用,提示其在非癌性疾病中也具有生理功能。尽管有报道称SPOCK1由人脂肪细胞分泌,但其在脂肪细胞生理中的作用尚未得到解决。本研究证实了SPOCK1蛋白在正常日粮(ND)喂养小鼠的胰腺、脂肪组织、脾脏和肝脏中的表达。有趣的是,SPOCK1在高脂肪饮食(HFD)喂养小鼠的胰腺和脂肪组织中表达上调。Spock1-Tg小鼠经ND喂养后,附睾和腹股沟脂肪组织成熟程度增加。此外,Spock1过表达强烈降低了脂肪组织中UCP-1的表达,提示Spock1可能通过抑制UCP-1的表达来调节产热功能。最后,外源SPOCK1处理直接加速了3T3-L1脂肪细胞的分化,同时伴随着脂肪细胞分化相关基因表达的上调。总之,我们首次证明SPOCK1通过上调脂肪形成相关基因诱导脂肪细胞分化。(C) 2020爱思唯尔公司版权所有。
SPOCK1 is a calcium-binding matricellular proteoglycan that has been extensively studied in several cancer cells. Previously, we generated a mouse line overexpressing SPOCK1 (Spock1-Tg mouse) and showed that SPOCK1 might play an important role in drug-induced gingival overgrowth, indicating that it possesses physiological functions in non-cancer diseases as well. Although SPOCK1 was reported to be secreted from human adipocytes, its role in adipocyte physiology has not been addressed yet. In this study, SPOCK1 protein expression was confirmed in pancreas, adipose tissues, spleen, and liver of normal diet (ND)-fed mice. Interestingly, SPOCK1 was up-regulated in the pancreas and adipose tissues of the high-fat diet (HFD)-fed mice. Spock1-Tg mice fed with ND showed increased maturation in epididymal and inguinal adipose tissues. In addition, Spock1 overexpression strongly decreased expression of UCP-1 in adipose tissues, suggesting that SPOCK1 might regulate thermogenic function through suppression of UCP-1 expression. Finally, exogenous SPOCK1 treatment directly accelerated the differentiation of 3T3-L1 adipocytes, accompanied by the up-regulation of adipocyte differentiation-related gene expression. In conclusion, we demonstrated for the first time that SPOCK1 induced adipocyte differentiation via the upregulation of adipogenesis-related genes. (C) 2020 Elsevier Inc. All rights reserved.