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Creb-Pgc1α pathway modulates the interaction between lipid droplets and mitochondria and influences high fat diet-induced changes of lipid metabolism in the liver and isolated hepatocytes of yellow catfish.
The Journal of Nutritional Biochemistry ( IF 4.8 ) Pub Date : 2020-02-28 , DOI: 10.1016/j.jnutbio.2020.108364
Yu-Feng Song 1 , Christer Hogstrand 2 , Shi-Cheng Ling 1 , Guang-Hui Chen 1 , Zhi Luo 3
Affiliation  

Although the crucial role of lipid droplets (LDs), mitochondria (MT) and their interactions in regulating lipid metabolism are well accepted, the mechanism of LDs-MT interactions in high fat diet (HFD)-induced changes of lipid metabolism remains unknown. Thus, this study was conducted to determine the mechanism of LDs-MT interactions in HFD-induced changes of lipid accumulation. We found that HFD not only up-regulated the expression of key proteins linked with TAG biosynthesis, but also increased the expression of proteins involved in lipolysis and fatty acid (FA) oxidation in LDs, including Rab32 (the only Rab protein associated with the MT). FA-induced LDs accumulation coincided with increased mitochondrial biogenesis, suggesting the potential LDs-MT interaction in hepatocytes after FA incubation. Also, FA incubation markedly increased the localization of Rab32 into LDs and MT, which confirmed the LDs-MT interaction and indicated the involvement of Rab32 in LDs-MT interaction following FA incubation. Inhibitors of Creb-Pgc1α pathway significantly blocked the localization of Rab32 into LDs and MT, and significantly reduced FA-induced LDs lipolysis by targeting Atgl and Plin5. Meanwhile, the FA-enhanced LDs accumulation, and mitochondrial biogenesis, fusion and oxidation were also significantly repressed. These indicated the regulatory role of Creb-Pgc1α in Rab32-mediated LDs-MT interactions and lipolysis after FA incubation. Taken together, these results revealed a novel mechanism of HFD- and FA-induced LDs-MT interactions in regulating hepatic LDs lipolysis, which provided new insight into the crosstalk between LDs-MT interaction and their potential role in HFD-induced hepatic steatosis.



中文翻译:

Creb-Pgc1α途径调节脂质滴与线粒体之间的相互作用,并影响高脂饮食诱导的黄cat鱼肝脏和分离的肝细胞中脂质代谢的变化。

尽管脂质小滴(LDs),线粒体(MT)及其相互作用在调节脂质代谢中的关键作用已广为接受,但LDs-MT相互作用在高脂饮食(HFD)诱导的脂质代谢变化中的机制仍然未知。因此,进行了这项研究以确定在HFD诱导的脂质蓄积变化中LDs-MT相互作用的机制。我们发现,HFD不仅上调了与TAG生物合成相关的关键蛋白的表达,而且还增加了LD中参与脂解和脂肪酸(FA)氧化的蛋白的表达,包括Rab32(与MT相关的唯一Rab蛋白)。 )。FA诱导的LDs积累与线粒体生物发生增加同时发生,表明FA孵育后肝细胞中潜在的LDs-MT相互作用。也,FA孵育显着增加了Rab32在LDs和MT中的定位,这证实了LDs-MT相互作用,并表明FA孵育后Rab32参与了LDs-MT相互作用。Creb-Pgc1α途径的抑制剂可显着阻断Rab32在LD和MT中的定位,并通过靶向Atgl和Plin5显着减少FA诱导的LD脂解。同时,FA增强的LDs积累,以及线粒体的生物发生,融合和氧化也受到显着抑制。这些表明,FA孵育后,Creb-Pgc1α在Rab32介导的LDs-MT相互作用和脂解中的调节作用。综上所述,这些结果揭示了HFD和FA诱导的LDs-MT相互作用调节肝脏LDs脂解的新机制,

更新日期:2020-02-28
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