PMID- 23315130
OWN - NLM
STAT- MEDLINE
DCOM- 20140317
LR  - 20211021
IS  - 1573-9368 (Electronic)
IS  - 0962-8819 (Linking)
VI  - 22
IP  - 4
DP  - 2013 Aug
TI  - Cannabinoid receptor 1 promotes hepatic lipid accumulation and lipotoxicity 
      through the induction of SREBP-1c expression in zebrafish.
PG  - 823-38
LID - 10.1007/s11248-012-9685-0 [doi]
AB  - The activated cannabinoid receptor 1 (CB1R) is exclusively responsible for food 
      intake and weight gain and regulates several pathological features associated 
      with obesity in mammals. However, the precise role of CB1R in non-mammalian model 
      systems is poorly understood. To investigate the functions of CB1R in zebrafish 
      liver, we conditionally expressed CB1R proteins using a liver-specific Tet(off) 
      transgenic system. In this study, we found hepatic lipid accumulation in CB1R 
      transgenic zebrafish (CB) without doxycycline treatment (-Dox) and a suppression 
      of CB1R expression, resulting in the loss of lipid accumulation in the livers of 
      CB fish that received doxycycline treatment (+Dox). Oil Red O (ORO)-stained 
      hepatocytes were predominant in the liver buds of CB-Dox larvae, indicating that 
      CB1R functionally promotes lipid accumulation during CB hepatogenesis. More than 
      73 % of CB-Dox adults showed increased lipid content, which leads, in turn, to 
      steatosis. Liver histology and ORO staining of CB-Dox hepatocytes also indicated 
      the accumulation of fatty droplets in the CB liver samples, consistent with the 
      specific pathological features of liver steatosis or steatohepatitis. We also 
      found that hepatic CB1R overexpression accompanies the stimulation of the 
      lipogenic transcription factor SREBP-1c and its target enzymes, acetyl coenzyme-A 
      carboxylase-1 (ACC1) and fatty acid synthase (FAS), and increases de novo fatty 
      acid synthesis. This study is the first to report CB1R as a potential hepatic 
      stimulator for zebrafish liver steatosis.
FAU - Pai, Wan-Yu
AU  - Pai WY
AD  - Institute of Bioscience and Biotechnology, National Taiwan Ocean University, 2 
      Pei Ning Road, Keelung 20224, Taiwan.
FAU - Hsu, Chia-Chun
AU  - Hsu CC
FAU - Lai, Chi-Yu
AU  - Lai CY
FAU - Chang, Trent-Zarng
AU  - Chang TZ
FAU - Tsai, Yu-Lun
AU  - Tsai YL
FAU - Her, Guor Mour
AU  - Her GM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130112
PL  - Netherlands
TA  - Transgenic Res
JT  - Transgenic research
JID - 9209120
RN  - 0 (Cnr1 protein, rat)
RN  - 0 (Lipids)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Hepatocytes/metabolism
MH  - Humans
MH  - Lipid Metabolism/*genetics
MH  - Lipids/toxicity
MH  - Liver/*metabolism
MH  - Obesity/*genetics/metabolism
MH  - Receptor, Cannabinoid, CB1/genetics/*metabolism
MH  - Sterol Regulatory Element Binding Protein 1/*genetics/metabolism
MH  - Zebrafish/genetics/metabolism
EDAT- 2013/01/15 06:00
MHDA- 2014/03/19 06:00
CRDT- 2013/01/15 06:00
PHST- 2012/10/11 00:00 [received]
PHST- 2012/12/28 00:00 [accepted]
PHST- 2013/01/15 06:00 [entrez]
PHST- 2013/01/15 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
AID - 10.1007/s11248-012-9685-0 [doi]
PST - ppublish
SO  - Transgenic Res. 2013 Aug;22(4):823-38. doi: 10.1007/s11248-012-9685-0. Epub 2013 
      Jan 12.