PMID- 27188441
OWN - NLM
STAT- MEDLINE
DCOM- 20171129
LR  - 20211204
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 9
IP  - 428
DP  - 2016 May 17
TI  - BTG1 ameliorates liver steatosis by decreasing stearoyl-CoA desaturase 1 (SCD1) 
      abundance and altering hepatic lipid metabolism.
PG  - ra50
LID - 10.1126/scisignal.aad8581 [doi]
AB  - Liver steatosis, a condition in which lipid accumulates in liver cells, is a 
      leading cause of many liver diseases. The livers of patients with hepatocellular 
      carcinoma, a cancer characterized by liver steatosis, have decreased abundance of 
      the transcription cofactor BTG1 (B cell translocation gene 1). We showed that the 
      livers of db/db mice, which are a genetic model of obesity, had decreased BTG1 
      mRNA and protein abundance. BTG1 overexpression ameliorated liver steatosis in 
      db/db mice, whereas knockdown of BTG1 induced liver steatosis in wild-type mice. 
      Consistent with these changes, we found that BTG1 decreased triglyceride 
      accumulation in cultured hepatocytes. BTG1 overexpression inhibited the 
      expression of the gene encoding stearoyl-CoA desaturase 1 (SCD1), an enzyme 
      involved in the synthesis of fatty acids, by suppressing the activity of 
      activating transcription factor 4 (ATF4). Knockdown of SCD1 prevented liver 
      steatosis in wild-type mice induced by knockdown of BTG1. Conversely, the ability 
      of BTG1 overexpression to ameliorate liver steatosis in db/db mice was negated by 
      ATF4 overexpression. Moreover, BTG1 transgenic mice were resistant to liver 
      steatosis induced by a high-carbohydrate diet. BTG1 abundance was decreased by 
      this diet through a pathway that involved mammalian target of rapamycin (mTOR), 
      ribosomal protein S6 kinase 1 (S6K1), and cAMP response element-binding protein 
      (CREB). Together, our study identifies a role of BTG1 in regulating hepatic lipid 
      metabolism and specifically in preventing ATF4 and SCD1 from inducing liver 
      steatosis.
CI  - Copyright (c) 2016, American Association for the Advancement of Science.
FAU - Xiao, Fei
AU  - Xiao F
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Deng, Jiali
AU  - Deng J
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Guo, Yajie
AU  - Guo Y
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Niu, Yuguo
AU  - Niu Y
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Yuan, Feixiang
AU  - Yuan F
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Yu, Junjie
AU  - Yu J
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Chen, Shanghai
AU  - Chen S
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Guo, Feifan
AU  - Guo F
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. 
      ffguo@sibs.ac.cn.
LA  - eng
PT  - Journal Article
DEP - 20160517
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Atf4 protein, mouse)
RN  - 0 (Btg1 protein, mouse)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Fatty Acids)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Triglycerides)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - EC 1.14.19.1 (Scd1 protein, mouse)
RN  - EC 1.14.19.1 (Stearoyl-CoA Desaturase)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Activating Transcription Factor 4/*metabolism
MH  - Animals
MH  - Carcinoma, Hepatocellular/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Fatty Acids/metabolism
MH  - Fatty Liver/*metabolism
MH  - HEK293 Cells
MH  - Hepatocytes/metabolism
MH  - Humans
MH  - *Lipid Metabolism
MH  - Liver/*metabolism
MH  - Liver Neoplasms/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/*metabolism
MH  - Obesity/metabolism
MH  - RNA, Messenger/metabolism
MH  - Stearoyl-CoA Desaturase/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Triglycerides/metabolism
EDAT- 2016/05/18 06:00
MHDA- 2017/12/01 06:00
CRDT- 2016/05/19 06:00
PHST- 2016/05/19 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/12/01 06:00 [medline]
AID - 9/428/ra50 [pii]
AID - 10.1126/scisignal.aad8581 [doi]
PST - epublish
SO  - Sci Signal. 2016 May 17;9(428):ra50. doi: 10.1126/scisignal.aad8581.