PMID- 30261661
OWN - NLM
STAT- MEDLINE
DCOM- 20190110
LR  - 20190110
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 10
DP  - 2018 Sep 26
TI  - Fc Gamma Receptor IIb Expressed in Hepatocytes Promotes Lipid Accumulation and 
      Gluconeogenesis.
LID - 10.3390/ijms19102932 [doi]
LID - 2932
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid 
      accumulation in the liver, usually combined with hepatic insulin resistance. 
      Fc-gamma receptor-IIb (FcgammaRIIb) and its ligand are reported to be associated with 
      obesity and type 2 diabetes mellitus (T2DM). As knowledge about FcgammaRIIb in the 
      literature is mostly generated from studies on skeletal muscle tissue, the 
      expression and function of FcgammaRIIb in the liver and hepatocytes are largely 
      unknown. In this study, we identified the expression of FcgammaRIIb in primary 
      cultured mouse hepatocytes: FcgammaRIIb was upregulated in response to oleic acid 
      (OA) in a dose dependent manner. FcgammaRIIb knockdown using shRNA suppressed the 
      lipid and triglyceride accumulation, and mRNA expression of ACC1, FASn, CD36, 
      MTTP, and ApoB in OA-treated HepG2 cells. FcgammaRIIb deficiency mice fed with high 
      fat diet (HFD) had significantly lower liver weight and liver to body weight 
      ratio, as well as less triglyceride accumulation in the livers. In 
      glycometabolism, FcgammaRIIb hindered insulin-induced phosphorylation of AKT and 
      FOXO1, and in turn upregulated G6Pase and PEPCK mRNA expression, suggesting that 
      FcgammaRIIb promotes gluconeogenesis by suppressing the AKT/FOXO1/G6Pase/PEPCK 
      pathway in hepatocytes. This study reveals a novel role for FcgammaRIIb in regulating 
      lipid metabolism and glycometabolism, and provides a new therapeutic target to 
      improve NAFLD.
FAU - Shu, Ting
AU  - Shu T
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, 
      Peking Union Medical College, Beijing 100005, China. 15901356250@126.com.
FAU - Song, Xiaomin
AU  - Song X
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, 
      Peking Union Medical College, Beijing 100005, China. 18271392658@163.com.
FAU - Cui, Xingxing
AU  - Cui X
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, 
      Peking Union Medical College, Beijing 100005, China. cuixingxing90@163.com.
FAU - Ge, Weipeng
AU  - Ge W
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, 
      Peking Union Medical College, Beijing 100005, China. 18840827758@163.com.
FAU - Gao, Ran
AU  - Gao R
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, 
      Peking Union Medical College, Beijing 100005, China. gaoran@ibms.pumc.edu.cn.
FAU - Wang, Jing
AU  - Wang J
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, 
      Peking Union Medical College, Beijing 100005, China. wangjing@ibms.pumc.edu.cn.
LA  - eng
GR  - 81622008, 81470579, 91739107/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20180926
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Fc gamma receptor IIB)
RN  - 0 (Receptors, IgG)
RN  - 0 (Triglycerides)
RN  - 2UMI9U37CP (Oleic Acid)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Gene Expression
MH  - Gluconeogenesis/drug effects/*genetics
MH  - Hep G2 Cells
MH  - Hepatocytes/*metabolism
MH  - Humans
MH  - Lipid Metabolism/drug effects/*genetics
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oleic Acid/pharmacology
MH  - RNA Interference
MH  - Receptors, IgG/*genetics/metabolism
MH  - Triglycerides/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC6213401
OTO - NOTNLM
OT  - FcgammaRIIb
OT  - NAFLD
OT  - gluconeogenesis
OT  - insulin sensitivity
COIS- The authors declare no conflicts of interest.
EDAT- 2018/09/29 06:00
MHDA- 2019/01/11 06:00
PMCR- 2018/10/01
CRDT- 2018/09/29 06:00
PHST- 2018/08/10 00:00 [received]
PHST- 2018/09/03 00:00 [revised]
PHST- 2018/09/08 00:00 [accepted]
PHST- 2018/09/29 06:00 [entrez]
PHST- 2018/09/29 06:00 [pubmed]
PHST- 2019/01/11 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - ijms19102932 [pii]
AID - ijms-19-02932 [pii]
AID - 10.3390/ijms19102932 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Sep 26;19(10):2932. doi: 10.3390/ijms19102932.