PMID- 21885686
OWN - NLM
STAT- MEDLINE
DCOM- 20120124
LR  - 20220409
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 301
IP  - 6
DP  - 2011 Dec
TI  - Estrogen deficiency worsens steatohepatitis in mice fed high-fat and 
      high-cholesterol diet.
PG  - G1031-43
LID - 10.1152/ajpgi.00211.2011 [doi]
AB  - Recent studies indicate an accelerated progression of nonalcoholic 
      steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an 
      important risk factor for NASH progression, is often observed after menopause. 
      This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice 
      fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of 
      estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or 
      HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen 
      replenishment, OVX mice fed with HFHC diet were treated with implanted hormone 
      release pellets (containing 17beta-estradiol or placebo vehicle) for 6 wk. OVX mice 
      on the HFHC diet showed enhanced liver injury with increased liver macrophage 
      infiltration and elevated serum cholesterol levels compared with SO-HFHC mice. 
      Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein expression in 
      OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In addition, hepatic 
      inflammatory gene expressions, including monocytes chemokine (C-C motif) receptor 
      2 (CCR2), were significantly elevated in OVX-HFHC mice. Estrogen treatment 
      improved serum cholesterol levels, liver injury, macrophage infiltration, and 
      inflammatory gene expressions in OVX-HFHC mice. Moreover, the elevated expression 
      of liver CCR2 and MCP1 were decreased by estrogen treatment in OVX-HFHC mice, 
      whereas low-density lipoprotein dose dependently enhanced CCR2 expression in THP1 
      monocytes. Our study demonstrated that estrogen deficiency accelerated NASH 
      progression in OVX mice fed HFHC diet and that this effect was improved by 
      estrogen therapy. Hypercholesterolemia in postmenopausal women would be a 
      potential risk factor for NASH progression.
FAU - Kamada, Yoshihiro
AU  - Kamada Y
AD  - Department of Gastroenterology and Hepatology, Osaka University, Graduate School 
      of Medicine, Suita, Osaka, Japan.
FAU - Kiso, Shinichi
AU  - Kiso S
FAU - Yoshida, Yuichi
AU  - Yoshida Y
FAU - Chatani, Norihiro
AU  - Chatani N
FAU - Kizu, Takashi
AU  - Kizu T
FAU - Hamano, Mina
AU  - Hamano M
FAU - Tsubakio, Mayumi
AU  - Tsubakio M
FAU - Takemura, Takayo
AU  - Takemura T
FAU - Ezaki, Hisao
AU  - Ezaki H
FAU - Hayashi, Norio
AU  - Hayashi N
FAU - Takehara, Tetsuo
AU  - Takehara T
LA  - eng
PT  - Journal Article
DEP - 20110901
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Estrogens)
RN  - 0 (Lipoproteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (lipoprotein cholesterol)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - Cholesterol/blood
MH  - Cholesterol, Dietary/*pharmacology
MH  - *Diet, High-Fat
MH  - Estrogens/*deficiency/pharmacology
MH  - Fatty Liver/drug therapy/epidemiology/*metabolism
MH  - Female
MH  - Gene Expression/physiology
MH  - Lipoproteins/blood
MH  - Liver/physiology
MH  - Liver Cirrhosis/drug therapy/epidemiology/metabolism
MH  - Macrophages/pathology/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/pathology/physiology
MH  - Non-alcoholic Fatty Liver Disease
MH  - Ovariectomy
MH  - Postmenopause/*metabolism
MH  - Receptors, CCR2/genetics
MH  - Risk Factors
EDAT- 2011/09/03 06:00
MHDA- 2012/01/25 06:00
CRDT- 2011/09/03 06:00
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2012/01/25 06:00 [medline]
AID - ajpgi.00211.2011 [pii]
AID - 10.1152/ajpgi.00211.2011 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2011 Dec;301(6):G1031-43. doi: 
      10.1152/ajpgi.00211.2011. Epub 2011 Sep 1.