TY - JOUR
T1 - Differential roles of cell death-inducing DNA fragmentation factor-α-like effector (CIDE) proteins in promoting lipid droplet fusion and growth in subpopulations of hepatocytes
AU - Xu, Wenyi
AU - Wu, Lizhen
AU - Yu, Miao
AU - Chen, Feng Jung
AU - Arshad, Muhammad
AU - Xia, Xiayu
AU - Ren, Hao
AU - Yu, Jinhai
AU - Xu, Li
AU - Xu, Dijin
AU - Li, John Zhong
AU - Li, Peng
AU - Zhou, Linkang
N1 - Funding Information:
This work was supported by National Basic Research Program Grants 2013CB530602 (to P. L.), National Natural Science Foundation of China Grants 31430040 and 31321003 (to P. L.) and Grant 31501089 (to J. Y.), and Grants 31271268 and 81471079 (to J. Z. L.), and China Postdoctoral Science Foundation Grants 2012M520249 and 2013T60103 (to L. Z.). The authors declare that they have no conflicts of interest regarding the contents of this article.
PY - 2016/2/26
Y1 - 2016/2/26
N2 - Lipid droplets (LDs) are dynamic subcellular organelles whose growth is closely linked to obesity and hepatic steatosis. Cell death-inducing DNA fragmentation factor-α-like effector (CIDE) proteins, including Cidea, Cideb, and Cidec (also called Fsp27), play important roles in lipid metabolism. Cidea and Cidec are LD-associated proteins that promote atypical LD fusion in adipocytes. Here, we find that CIDE proteins are all localized to LD-LD contact sites (LDCSs) and promote lipid transfer, LD fusion, and growth in hepatocytes. We have identified two types of hepatocytes, one with small LDs (small LDcontaining hepatocytes, SLHs) and one with large LDs (large LD-containing hepatocytes, LLHs) in the liver. Cideb is localized to LDCSs and promotes lipid exchange and LD fusion in both SLHs and LLHs, whereas Cidea and Cidec are specifically localized to the LDCSs and promote lipid exchange and LD fusion in LLHs. Cideb-deficient SLHs have reducedLDsizes and lower lipid exchange activities. Fasting dramatically induces the expression of Cidea/Cidec and increases the percentage of LLHs in the liver. The majority of the hepatocytes from the liver of obese mice are Cidea/Cidec-positive LLHs. Knocking down Cidea or Cidec significantly reduced lipid storage in the livers of obese animals. Our data reveal that CIDE proteins play differential roles in promoting LD fusion and lipid storage; Cideb promotes lipid storage under normal diet conditions, whereas Cidea and Cidec are responsible for liver steatosis under fasting and obese conditions.
AB - Lipid droplets (LDs) are dynamic subcellular organelles whose growth is closely linked to obesity and hepatic steatosis. Cell death-inducing DNA fragmentation factor-α-like effector (CIDE) proteins, including Cidea, Cideb, and Cidec (also called Fsp27), play important roles in lipid metabolism. Cidea and Cidec are LD-associated proteins that promote atypical LD fusion in adipocytes. Here, we find that CIDE proteins are all localized to LD-LD contact sites (LDCSs) and promote lipid transfer, LD fusion, and growth in hepatocytes. We have identified two types of hepatocytes, one with small LDs (small LDcontaining hepatocytes, SLHs) and one with large LDs (large LD-containing hepatocytes, LLHs) in the liver. Cideb is localized to LDCSs and promotes lipid exchange and LD fusion in both SLHs and LLHs, whereas Cidea and Cidec are specifically localized to the LDCSs and promote lipid exchange and LD fusion in LLHs. Cideb-deficient SLHs have reducedLDsizes and lower lipid exchange activities. Fasting dramatically induces the expression of Cidea/Cidec and increases the percentage of LLHs in the liver. The majority of the hepatocytes from the liver of obese mice are Cidea/Cidec-positive LLHs. Knocking down Cidea or Cidec significantly reduced lipid storage in the livers of obese animals. Our data reveal that CIDE proteins play differential roles in promoting LD fusion and lipid storage; Cideb promotes lipid storage under normal diet conditions, whereas Cidea and Cidec are responsible for liver steatosis under fasting and obese conditions.
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U2 - 10.1074/jbc.M115.701094
DO - 10.1074/jbc.M115.701094
M3 - Article
C2 - 26733203
AN - SCOPUS:84964746693
SN - 0021-9258
VL - 291
SP - 4282
EP - 4293
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -