PMID- 23417738
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20220408
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 54
IP  - 5
DP  - 2013 May
TI  - Hepatic cholesterol crystals and crown-like structures distinguish NASH from 
      simple steatosis.
PG  - 1326-34
LID - 10.1194/jlr.M034876 [doi]
AB  - We sought to determine whether hepatic cholesterol crystals are present in 
      patients or mice with nonalcoholic fatty liver disease/nonalcoholic 
      steatohepatitis (NASH), and whether their presence or distribution correlates 
      with the presence of NASH as compared with simple steatosis. We identified, by 
      filipin staining, free cholesterol within hepatocyte lipid droplets in patients 
      with NASH and in C57BL/6J mice that developed NASH following a high-fat 
      high-cholesterol diet. Under polarized light these lipid droplets exhibited 
      strong birefringence suggesting that some of the cholesterol was present in the 
      form of crystals. Activated Kupffer cells aggregated around dead hepatocytes that 
      included strongly birefringent cholesterol crystals, forming "crown-like 
      structures" similar to those recently described in inflamed visceral adipose 
      tissue. These Kupffer cells appeared to process the lipid of dead hepatocytes 
      turning it into activated lipid-laden "foam cells" with numerous small 
      cholesterol-containing droplets. In contrast, hepatocyte lipid droplets in 
      patients and mice with simple steatosis did not exhibit cholesterol crystals and 
      their Kupffer cells did not form crown-like structures or transform into foam 
      cells. Our results suggest that cholesterol crystallization within hepatocyte 
      lipid droplets and aggregation and activation of Kupffer cells in crown-like 
      structures around such droplets represent an important, novel mechanism for 
      progression of simple steatosis to NASH.
FAU - Ioannou, George N
AU  - Ioannou GN
AD  - Research Enhancement Award Program and Veterans Affairs Puget Sound Health Care 
      System, Seattle, WA, USA. georgei@medicine.washington.edu
FAU - Haigh, W Geoffrey
AU  - Haigh WG
FAU - Thorning, David
AU  - Thorning D
FAU - Savard, Christopher
AU  - Savard C
LA  - eng
GR  - P30 DK017047/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130217
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Lipids)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Cell Aggregation
MH  - Cholesterol/chemistry/*metabolism
MH  - Diagnosis, Differential
MH  - Diet, High-Fat
MH  - Fatty Liver/diagnosis/*metabolism/pathology
MH  - Hepatocytes/chemistry/*metabolism
MH  - Humans
MH  - Kupffer Cells/chemistry/metabolism
MH  - Lipids/analysis
MH  - Liquid Crystals/chemistry
MH  - Male
MH  - Mice
MH  - Non-alcoholic Fatty Liver Disease
PMC - PMC3622327
EDAT- 2013/02/19 06:00
MHDA- 2013/11/05 06:00
PMCR- 2014/05/01
CRDT- 2013/02/19 06:00
PHST- 2013/02/19 06:00 [entrez]
PHST- 2013/02/19 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - S0022-2275(20)42170-4 [pii]
AID - m034876 [pii]
AID - 10.1194/jlr.M034876 [doi]
PST - ppublish
SO  - J Lipid Res. 2013 May;54(5):1326-34. doi: 10.1194/jlr.M034876. Epub 2013 Feb 17.