Center for Gene and Immunotherapy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Urology, College of Medicine, University of Florida, Gainesville, FL, United States.
Front Endocrinol (Lausanne). 2022 Mar 7;13:852015. doi: 10.3389/fendo.2022.852015. eCollection 2022.
FNDC5 is the precursor of the myokine irisin proposed to exhibit favorable metabolic activity, including anti-obesity and anti-diabetes effects. The diversity of FNDC5 transcripts has been reported by several studies, but the role and existence of these transcripts are not well defined. In our previous study, a novel secretable FNDC5 (sFNDC5) isoform lacking the transmembrane region was found in rat INS-1 cells and multiple rat tissues. In the current study, we established a high-yield system for the expression and purification of sFNDC5 in , and functional investigations were undertaken using 3T3-L1 cells. We discovered that this new isoform has similar and even stronger biological functions than irisin, which may be due to its more complete structure without cleavage. Hence, we believe that sFNDC5, as the first identified readily secretable derivative, can better induce lipolysis and can potentially prevent obesity and related metabolic diseases.
FNDC5 是肌肽的前体,被认为具有有利的代谢活性,包括抗肥胖和抗糖尿病作用。FNDC5 转录本的多样性已被多项研究报道,但这些转录本的作用和存在尚不清楚。在我们之前的研究中,在大鼠 INS-1 细胞和多种大鼠组织中发现了一种新型可分泌的 FNDC5(sFNDC5)同工型,缺乏跨膜区域。在本研究中,我们建立了在 中表达和纯化 sFNDC5 的高产系统,并使用 3T3-L1 细胞进行了功能研究。我们发现,这种新的同工型具有与 Irisin 相似甚至更强的生物学功能,这可能是由于其结构更完整,无需切割。因此,我们认为 sFNDC5 作为第一个被鉴定的可分泌衍生物,可以更好地诱导脂肪分解,并可能预防肥胖和相关代谢疾病。