PMID- 18166358
OWN - NLM
STAT- MEDLINE
DCOM- 20080205
LR  - 20211203
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 134
IP  - 1
DP  - 2008 Jan
TI  - PTEN down-regulation by unsaturated fatty acids triggers hepatic steatosis via an 
      NF-kappaBp65/mTOR-dependent mechanism.
PG  - 268-80
LID - 10.1053/j.gastro.2007.10.010 [doi]
AB  - BACKGROUND & AIMS: Phosphatase and tensin homologue deleted on chromosome 10 
      (PTEN) is a tumor suppressor and a regulator of insulin sensitivity in peripheral 
      tissues. In the liver, PTEN deletion increases insulin sensitivity, but induces 
      steatosis, steatohepatitis, and hepatocellular carcinoma. Here, we investigated 
      the pathophysiologic mechanisms regulating PTEN expression in the liver and the 
      development of steatosis. METHODS: PTEN expression was evaluated in the liver of 
      rats and human beings having metabolic syndrome. Signaling pathways regulating 
      PTEN expression and lipid accumulation in hepatocytes were examined in vitro. 
      RESULTS: PTEN expression is down-regulated in the liver of rats having steatosis 
      and high plasma levels of fatty acids, as well as in steatotic human livers. 
      Unsaturated fatty acids inhibited PTEN expression in HepG2 cells via activation 
      of a signaling complex formed by the mammalian target of rapamycin (mTOR) and 
      nuclear factor-kappaB (NF-kappaB). Down-regulation of PTEN expression induced 
      steatosis by affecting import, esterification, and extracellular release of fatty 
      acids. CONCLUSIONS: Hepatic steatosis can be mediated by alterations of PTEN 
      expression in hepatocytes exposed to high levels of unsaturated fatty acids. 
      Furthermore, our data revealed interaction between mTOR and NF-kappaB, suggesting 
      cross-talk between these 2 pathways.
FAU - Vinciguerra, Manlio
AU  - Vinciguerra M
AD  - Department of Cell Physiology and Metabolism, Geneva Medical Faculty, Geneva 
      University Hospital, Switzerland.
FAU - Veyrat-Durebex, Christelle
AU  - Veyrat-Durebex C
FAU - Moukil, Moulay Ahmed
AU  - Moukil MA
FAU - Rubbia-Brandt, Laura
AU  - Rubbia-Brandt L
FAU - Rohner-Jeanrenaud, Francoise
AU  - Rohner-Jeanrenaud F
FAU - Foti, Michelangelo
AU  - Foti M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071010
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Transcription Factor RelA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques
MH  - Disease Models, Animal
MH  - Fatty Acids, Unsaturated/*pharmacology
MH  - Fatty Liver/*etiology
MH  - Hepatocytes/*drug effects/physiology
MH  - Humans
MH  - Liver/*metabolism
MH  - Metabolic Syndrome/*metabolism
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Protein Kinases/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Rats, Zucker
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factor RelA/physiology
EDAT- 2008/01/02 09:00
MHDA- 2008/02/06 09:00
CRDT- 2008/01/02 09:00
PHST- 2007/04/05 00:00 [received]
PHST- 2007/09/28 00:00 [accepted]
PHST- 2008/01/02 09:00 [pubmed]
PHST- 2008/02/06 09:00 [medline]
PHST- 2008/01/02 09:00 [entrez]
AID - S0016-5085(07)01809-4 [pii]
AID - 10.1053/j.gastro.2007.10.010 [doi]
PST - ppublish
SO  - Gastroenterology. 2008 Jan;134(1):268-80. doi: 10.1053/j.gastro.2007.10.010. Epub 
      2007 Oct 10.