PMID- 25915743
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150428
LR  - 20181113
IS  - 2044-4052 (Print)
IS  - 2044-4052 (Electronic)
IS  - 2044-4052 (Linking)
VI  - 5
IP  - 4
DP  - 2015 Apr 27
TI  - Effect of multiple binge alcohol on diet-induced liver injury in a mouse model of 
      obesity.
PG  - e154
LID - 10.1038/nutd.2015.4 [doi]
AB  - BACKGROUND: Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease 
      (NAFLD) are highly prevalent liver diseases that may coexist and contribute 
      significantly to liver disease-related mortality. Obesity is a common underlying 
      risk factor for both disorders. There has been little research investigating the 
      combined effects of high fat diet (HFD) and alcohol. Current mouse models of 
      alcohol- or fat-rich diet alone do not lead to severe liver injury. There is a 
      need to develop animal models recapitulating human settings of drinking and diet 
      to study the mechanisms of liver injury progression. METHODS: C57BL6 male mice 
      were fed either chow or HFD ad libitum for 12 weeks. A sub-set of mice from each 
      group were also given alcohol (2 g kg(-)(1) body weight) twice a week via 
      intra-gastric lavage. Animals were monitored progressively for weight gain and 
      blood and livers were harvested at termination. The extent of liver injury was 
      examined by histopathology as well as by liver and serum biochemistry. The 
      expression of lipid metabolism, inflammation and fibrogenesis-related molecules 
      was examined by quantitative reverse transcription PCR (Q-PCR) and 
      immunofluorescence staining. RESULTS: HFD significantly increased total body 
      weight, triglyceride and cholesterol, whereas alcohol increased liver weight. 
      Alcohol+HFD in combination produced maximum hepatic steatosis, increased micro- 
      and macro-vesicular lipid droplets, increased de novo lipogenesis (steroid 
      response-element binding protein 1 (SREBP-1) and stearoyl-CoA desaturase-1 
      (SCD-1)) and proliferation peroxisome activated receptor alpha (PPARalpha), and 
      decreased fatty acid beta-oxidation (Acyl-CoA oxidase 1 (ACOX1)). Alcohol+HFD 
      treatment also increased the inflammation (CD45+, CD68+, F4/80+ cells; tumour 
      necrosis factor-alpha (TNF-alpha), F4/80 mRNAs) and fibrogenesis (vimentin+ activated 
      stellate cells, collagen 1 (Col1) production, transforming growth factor-beta 
      (TGF-beta) and Col-1 mRNAs) in mice livers. CONCLUSIONS: We report a novel mouse 
      model with more severe liver injury than either alcohol or HFD alone 
      recapitulating the human setting of intermittent alcohol drinking and HFD.
FAU - Duly, A M P
AU  - Duly AM
AD  - Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, NSW, 
      Australia.
FAU - Alani, B
AU  - Alani B
AD  - Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, NSW, 
      Australia.
FAU - Huang, E Y-W
AU  - Huang EY
AD  - Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, NSW, 
      Australia.
FAU - Yee, C
AU  - Yee C
AD  - Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW, 
      Australia.
FAU - Haber, P S
AU  - Haber PS
AD  - 1] Sydney Medical School, University of Sydney, Sydney, NSW, Australia [2] Drug 
      Health Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
FAU - McLennan, S V
AU  - McLennan SV
AD  - 1] Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW, 
      Australia [2] Sydney Medical School, University of Sydney, Sydney, NSW, 
      Australia.
FAU - Seth, D
AU  - Seth D
AD  - 1] Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, NSW, 
      Australia [2] Sydney Medical School, University of Sydney, Sydney, NSW, Australia 
      [3] Drug Health Services, Royal Prince Alfred Hospital, Camperdown, NSW, 
      Australia.
LA  - eng
PT  - Journal Article
DEP - 20150427
PL  - England
TA  - Nutr Diabetes
JT  - Nutrition & diabetes
JID - 101566341
PMC - PMC4423200
EDAT- 2015/04/29 06:00
MHDA- 2015/04/29 06:01
PMCR- 2015/04/01
CRDT- 2015/04/28 06:00
PHST- 2015/01/02 00:00 [received]
PHST- 2015/02/16 00:00 [revised]
PHST- 2015/03/30 00:00 [accepted]
PHST- 2015/04/28 06:00 [entrez]
PHST- 2015/04/29 06:00 [pubmed]
PHST- 2015/04/29 06:01 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - nutd20154 [pii]
AID - 10.1038/nutd.2015.4 [doi]
PST - epublish
SO  - Nutr Diabetes. 2015 Apr 27;5(4):e154. doi: 10.1038/nutd.2015.4.