PMID- 21847582
OWN - NLM
STAT- MEDLINE
DCOM- 20120301
LR  - 20211020
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 54
IP  - 11
DP  - 2011 Nov
TI  - Altered endocannabinoid signalling after a high-fat diet in Apoe(-/-) mice: 
      relevance to adipose tissue inflammation, hepatic steatosis and insulin 
      resistance.
PG  - 2900-10
LID - 10.1007/s00125-011-2274-6 [doi]
AB  - AIMS/HYPOTHESIS: Apolipoprotein E (ApoE) deficiency is associated with reduced 
      fat accumulation in white adipose tissue (WAT) and high liver triacylglycerol 
      content. Elevated levels of endocannabinoids and cannabinoid receptor type 1 
      (CB(1)) receptors in the liver and in epididymal vs subcutaneous WAT are 
      associated with fatty liver, visceral adipose tissue, inflammatory markers and 
      insulin resistance. METHODS: We investigated, in Apoe (-/-) and wild-type (WT) 
      mice, the effect of a high-fat diet (HFD) on: (1) subcutaneous and epididymal WAT 
      accumulation, liver triacylglycerols, phospholipid-esterified fatty acids, 
      inflammatory markers in WAT and liver, and insulin resistance; and (2) 
      endocannabinoid levels, and the gene expression levels of the Cb ( 1 ) receptor 
      and endocannabinoid metabolic enzymes in liver and WAT. RESULTS: After a 16 week 
      HFD, Apoe (-/-) mice exhibited lower body weight, WAT accumulation and fasting 
      leptin, glucose and insulin levels, and higher hepatic steatosis, than WT mice. 
      Glucose clearance and insulin-mediated glucose disposal following the HFD were 
      slower in WT than Apoe (-/-) mice, which exhibited higher levels of mRNA encoding 
      inflammatory markers (tumour necrosis factor-alpha [TNF-alpha], monocyte chemoattractant 
      protein-1 [MCP-1], cluster of differentiation 68 [CD68] and EGF-like 
      module-containing mucin-like hormone receptor-like 1 [EMR1]) in the liver, but 
      lower levels in epididymal WAT. HFD-induced elevation of endocannabinoid levels 
      in the liver or epididymal WAT was higher or lower, respectively, in Apoe (-/-) 
      mice, whereas HFD-induced decrease of subcutaneous WAT endocannabinoid and CB(1) 
      receptor levels was significantly less marked. Alterations in endocannabinoid 
      levels reflected changes in endocannabinoid catabolic enzymes in WAT, or the 
      availability of phospholipid precursors in the liver. CONCLUSIONS/INTERPRETATION: 
      Liver and adipose tissue endocannabinoid tone following an HFD is altered on Apoe 
      deletion and strongly associated with inflammation, insulin resistance and 
      hepatic steatosis, or lack thereof.
FAU - Bartelt, A
AU  - Bartelt A
AD  - Department of Biochemistry and Molecular Cell Biology, University Medical Center 
      Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
FAU - Orlando, P
AU  - Orlando P
FAU - Mele, C
AU  - Mele C
FAU - Ligresti, A
AU  - Ligresti A
FAU - Toedter, K
AU  - Toedter K
FAU - Scheja, L
AU  - Scheja L
FAU - Heeren, J
AU  - Heeren J
FAU - Di Marzo, V
AU  - Di Marzo V
LA  - eng
GR  - DA-009789/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110817
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Apolipoproteins E)
RN  - 0 (Cannabinoid Receptor Modulators)
RN  - 0 (Dietary Fats)
RN  - 0 (Endocannabinoids)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Cannabinoid, CB1)
SB  - IM
MH  - Adipose Tissue, White/immunology/metabolism
MH  - Animals
MH  - Apolipoproteins E/genetics/*physiology
MH  - Cannabinoid Receptor Modulators/*metabolism
MH  - Cells, Cultured
MH  - Dietary Fats/*adverse effects
MH  - *Endocannabinoids
MH  - Fatty Liver/immunology/*metabolism/pathology
MH  - Gene Expression Regulation
MH  - Hepatocytes/metabolism/pathology
MH  - Inflammation Mediators/metabolism
MH  - *Insulin Resistance
MH  - Lipid Metabolism
MH  - Liver/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Panniculitis/immunology/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, Cannabinoid, CB1/genetics/*metabolism
MH  - *Signal Transduction
MH  - Subcutaneous Fat/immunology/metabolism
EDAT- 2011/08/19 06:00
MHDA- 2012/03/02 06:00
CRDT- 2011/08/18 06:00
PHST- 2011/05/03 00:00 [received]
PHST- 2011/07/11 00:00 [accepted]
PHST- 2011/08/18 06:00 [entrez]
PHST- 2011/08/19 06:00 [pubmed]
PHST- 2012/03/02 06:00 [medline]
AID - 10.1007/s00125-011-2274-6 [doi]
PST - ppublish
SO  - Diabetologia. 2011 Nov;54(11):2900-10. doi: 10.1007/s00125-011-2274-6. Epub 2011 
      Aug 17.