title: 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.
abstract: 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 LD-containing 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 reduced LD sizes 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.
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Xu
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wu
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Feng-Jung
authors.initials: FJ
authors.lastname: Chen
authors.affiliation: the Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad 44000, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Arshad
authors.affiliation: the Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Xia
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Yu
authors.affiliation: the Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China, and.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Dijin
authors.initials: D
authors.lastname: Xu
authors.affiliation: the Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: John Zhong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, li-peng@mail.tsinghua.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: From the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, zhoulinkang@mail.tsinghua.edu.cn.
authors.forename: Linkang
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D005234:Fatty Liver / Q000209:etiology*; D005508:Food Deprivation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D066292:Lipid Droplets / Q000473:pathology* / Q000648:ultrastructure; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001678:Organelle Biogenesis; D053141:Organelle Size; D000070780:Perilipin-2; D021381:Protein Transport; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; C484761:Cideb protein, mouse; D008565:Membrane Proteins; D000070780:Perilipin-2; D011506:Proteins; D011993:Recombinant Fusion Proteins; C525805:fat-specific protein 27, mouse
keywords: CIDE proteins; cell biology; hepatic steatosis; lipid; lipid droplet; lipid droplet fusion; lipid metabolism; lipid storage; liver; metabolism