PMID- 27713108
OWN - NLM
STAT- MEDLINE
DCOM- 20170922
LR  - 20181113
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 125
IP  - 3
DP  - 2017 Mar
TI  - Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in 
      the C57BL/6J Diet-Induced Obesity Mouse Model.
PG  - 428-436
LID - 10.1289/EHP316 [doi]
AB  - BACKGROUND: Exposure to persistent organic pollutants (POPs) has been associated 
      with the progression of chronic liver diseases, yet the contribution of POPs to 
      the development of fibrosis in non-alcoholic fatty liver disease (NAFLD), a 
      condition closely linked to obesity, remains poorly documented. OBJECTIVES: We 
      investigated the effects of subchronic exposure to low doses of the POP 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor ligand, 
      on NAFLD progression in diet-induced obese C57BL/6J mice. METHODS: Male C57BL/6J 
      mice were fed either a 10% low-fat (LFD) or a 45% high-fat (HFD) purified diet 
      for 14 weeks and TCDD-exposed groups were injected once a week with 5 mug/kg TCDD 
      or the vehicle for the last 6 weeks of the diet. RESULTS: Liver histology and 
      triglyceride levels showed that exposure of HFD fed mice to TCDD worsened hepatic 
      steatosis, as compared to either HFD alone or LFD plus TCDD and the mRNA levels 
      of key genes of hepatic lipid metabolism were strongly altered in co-treated 
      mice. Further, increased liver collagen staining and serum transaminase levels 
      showed that TCDD induced liver fibrosis in the HFD fed mice. TCDD in LFD fed mice 
      increased the expression of several inflammation and fibrosis marker genes with 
      no additional effect from a HFD. CONCLUSIONS: Exposure to TCDD amplifies the 
      impairment of liver functions observed in mice fed an enriched fat diet as 
      compared to a low fat diet. The results provide new evidence that environmental 
      pollutants promote the development of liver fibrosis in obesity-related NAFLD in 
      C57BL/6J mice. Citation: Duval C, Teixeira-Clerc F, Leblanc AF, Touch S, Emond C, 
      Guerre-Millo M, Lotersztajn S, Barouki R, Aggerbeck M, Coumoul X. 2017. Chronic 
      exposure to low doses of dioxin promotes liver fibrosis development in the 
      C57BL/6J diet-induced obesity mouse model. Environ Health Perspect 
      125:428-436; http://dx.doi.org/10.1289/EHP316.
FAU - Duval, Caroline
AU  - Duval C
AD  - INSERM UMR (Institut National de la Sante et de la Recherche Medicale Unite Mixte 
      de Recherche)-S1124, Paris, France.
FAU - Teixeira-Clerc, Fatima
AU  - Teixeira-Clerc F
FAU - Leblanc, Alix F
AU  - Leblanc AF
FAU - Touch, Sothea
AU  - Touch S
FAU - Emond, Claude
AU  - Emond C
FAU - Guerre-Millo, Michele
AU  - Guerre-Millo M
FAU - Lotersztajn, Sophie
AU  - Lotersztajn S
FAU - Barouki, Robert
AU  - Barouki R
FAU - Aggerbeck, Martine
AU  - Aggerbeck M
FAU - Coumoul, Xavier
AU  - Coumoul X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161007
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Dioxins)
RN  - 0 (Environmental Pollutants)
SB  - IM
MH  - Animals
MH  - Dioxins/*toxicity
MH  - Disease Models, Animal
MH  - Environmental Pollutants/*toxicity
MH  - Liver Cirrhosis/*chemically induced
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Toxicity Tests, Chronic
PMC - PMC5332187
COIS- The authors declare they have no actual or potential competing financial 
      interests.
EDAT- 2016/10/08 06:00
MHDA- 2017/09/25 06:00
PMCR- 2017/03/01
CRDT- 2016/10/08 06:00
PHST- 2016/04/08 00:00 [received]
PHST- 2016/07/11 00:00 [revised]
PHST- 2016/08/19 00:00 [accepted]
PHST- 2016/10/08 06:00 [pubmed]
PHST- 2017/09/25 06:00 [medline]
PHST- 2016/10/08 06:00 [entrez]
PHST- 2017/03/01 00:00 [pmc-release]
AID - EHP316 [pii]
AID - 10.1289/EHP316 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2017 Mar;125(3):428-436. doi: 10.1289/EHP316. Epub 2016 
      Oct 7.