PMID- 29264491
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231112
IS  - 2472-1972 (Print)
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 1
IP  - 4
DP  - 2017 Apr 1
TI  - Developmental Exposure to 2,2',4,4'-Tetrabromodiphenyl Ether Induces Long-Lasting 
      Changes in Liver Metabolism in Male Mice.
PG  - 323-344
LID - 10.1210/js.2016-1011 [doi]
AB  - Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives in 
      a wide range of polymers. The generations born when environmental concentrations 
      of PBDEs reached their maximum account in the United States for one-fifth of the 
      total population. We hypothesized that exposure to PBDEs during sensitive 
      developmental windows might result in long-lasting changes in liver metabolism. 
      The present study was based on experiments with CD-1 mice and human 
      hepatocellular carcinoma cells (human hepatoma cell line, HepG2). Pregnant mice 
      were exposed to 0.2 mg/kg 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) from 
      gestation day 8 until postnatal day 21. The metabolic health-related outcomes 
      were analyzed on postnatal day 21 and postnatal week 20 in male offspring. 
      Several groups of metabolic genes, including ribosomal and mitochondrial genes, 
      were significantly upregulated in the liver at both points. Genes regulated via 
      mechanistic target of rapamycin (mTOR) pathway, the gatekeeper of metabolic 
      homeostasis, were whether up- or downregulated at both measurement points. On 
      postnatal day 21, but not week 20, both mTOR complexes in the liver were 
      activated, as measured by phosphorylation of their targets. mTOR complexes were 
      also activated by BDE-47 in HepG2 cells in vitro. The following changes were 
      observed at week 20: a decreased number of polyploid hepatocytes, suppressed 
      cytoplasmic S6K1, twofold greater blood insulin-like growth factor-1 and 
      triglycerides, and 2.5-fold lower expression of fatty acid uptake membrane 
      receptor CD36 in liver tissue. Thus, perinatal exposure to environmentally 
      relevant doses of BDE-47 in laboratory mice results in long-lasting changes in 
      liver physiology. Our evidence suggests involvement of the mTOR pathway in the 
      observed metabolic programming of the liver.
FAU - Khalil, Ahmed
AU  - Khalil A
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003.
AD  - Medical Biotechnology Department, Genetic Engineering and Biotechnology Research 
      Institute, City of Scientific Research and Technological Applications, Alexandria 
      21934, Egypt.
FAU - Parker, Mikhail
AU  - Parker M
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003.
FAU - Mpanga, Richard
AU  - Mpanga R
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003.
FAU - Cevik, Sebnem E
AU  - Cevik SE
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003.
FAU - Thorburn, Cassandra
AU  - Thorburn C
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003.
FAU - Suvorov, Alexander
AU  - Suvorov A
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003.
LA  - eng
PT  - Journal Article
DEP - 20170314
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC5686773
OTO - NOTNLM
OT  - Freeform/Key Words: polybrominated diphenyl ether
OT  - hyperlipidemia
OT  - mTOR
OT  - metabolism
OT  - ribosome
OT  - rodent
EDAT- 2017/12/22 06:00
MHDA- 2017/12/22 06:01
PMCR- 2017/03/14
CRDT- 2017/12/22 06:00
PHST- 2016/10/06 00:00 [received]
PHST- 2017/03/09 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/22 06:01 [medline]
PHST- 2017/03/14 00:00 [pmc-release]
AID - JS_161011 [pii]
AID - 10.1210/js.2016-1011 [doi]
PST - epublish
SO  - J Endocr Soc. 2017 Mar 14;1(4):323-344. doi: 10.1210/js.2016-1011. eCollection 
      2017 Apr 1.