Skip participates in formation and lipid metabolism of beige adipose and might mediate the effects of SIRT1 activator BTM-0512 on beige remodeling
Skip participates in formation and lipid metabolism of beige adipose and might mediate the effects of SIRT1 activator BTM-0512 on beige remodeling
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Skip 参与米色脂肪的形成和脂质代谢，并可能介导 SIRT1 激活剂 BTM-0512 对米色重塑的影响
DOI：
10.1016/j.bbrc.2020.12.058
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Yang, Zhi-Chun
中科院分区：
文献类型：
--
作者：
Liao, Zhi-Mei;Li, An-Na;Yang, Zhi-Chun
通过激活热源性脂肪来消耗能量以对抗肥胖引起了许多人的兴趣。ski - interaction protein （Skip）在细胞增殖和分化中起重要作用，但其是否参与能量代谢尚不清楚。我们前期研究发现BTM-0512可诱导米色脂肪形成，并伴有Skip的上调，但Skip在代谢中的作用尚不清楚。在本研究中，我们主要研究Skip是否参与皮下白色前脂肪细胞的米色重塑以及分化的米色脂肪细胞的脂质代谢。结果表明，在高脂饮食诱导的肥胖小鼠中，皮下和内脏白色脂肪以及棕色脂肪中Skip蛋白水平均下调，尤其是皮下白色脂肪。然后，我们培养了皮下脂肪干细胞（ADSCs），发现Skip （siSkip）的敲除抑制了未分化的ADSCs和分化的米色脂肪细胞中产热脂肪特异性基因PRDM16和UCP1的表达，从而可以消除bdm -0512对米色重塑的影响。我们进一步观察到siSkip影响了脂质代谢中的多种限速酶。siSkip下调ACC、GPAT-1、HSL和ATGL的表达，上调CPTl - a的表达。siSkip也降低了AMPK的表达。综上所述，我们的研究表明Skip可能在白色脂肪细胞的米色重塑以及米色脂肪的脂质代谢中发挥重要作用。(C) 2020爱思唯尔公司版权所有。
Dissipating energy by activating thermogenic adipose to combating obesity attracts many interests. Ski-interacting protein (Skip) has been known to play an important role in cell proliferation and differentiation, but whether it participates in energy metabolism is not known. Our previous study revealed that BTM-0512 could induce beige adipose formation, accompanying with up-regulation of Skip, but the role of Skip in metabolism was unknown. In this study, we mainly investigated whether Skip was involved in beige remodeling of subcutaneous white preadipocytes as well as in lipid metabolism of differentiated beige adipocytes. The results showed that in high fat diet-induced obesity mice, the protein levels of Skip in subcutaneous and visceral white adipose as well as in brown adipose were all down-regulated, especially in subcutaneous white adipose. Then we cultured subcutaneous adipose derived-stem cells (ADSCs) and found knock-down of Skip (siSkip) inhibited the expressions of thermogenic adipose specific genes including PRDM16 and UCP1 in both undifferentiated ADSCs and differentiated beige adipocytes, which could abolish the effects of BTM-0512 on beige remodeling. We further observed that siSkip affected multiple rate-limiting enzymes in lipid metabolism. The expressions of ACC, GPAT-1, HSL and ATGL were down-regulated, while CPTl a expression was up-regulated by siSkip. The expression of AMPK was also decreased by siSkip. In conclusion, our study demonstrated that Skip might play an important role in the beige remodeling of white adipocytes as well as lipid metabolism of beige adipose. (C) 2020 Elsevier Inc. All rights reserved.