Session: FP05-Lipids: Regulation & Mechanism of Disease
Room 133 (Moscone Center)
Poster Board SAT-726
Materials and methods: HepG2 cells were treated with palmitate (0,5 mmol/l) pre-conjugated with albumin, rapamycin (500 nmol/l) and/or AKT Inhibitor (100 nmol/l). Cells were also transfected with siRNA targeted to Raptor or a siRNA targeted to Rictor. A scrambled siRNA was used as control. mTORC2/AKT pathway and UPR were assessed by Western blotting. Cell death was assessed by DNA fragmentation.
Results: Palmitate-induced apoptosis was maximal after 12h of treatment. CHOP, a marker of ER-stress-dependent apoptosis was also modulated by palmitate and peaked 12h after exposition to palmitate. Processed ATF6 was upregulated 3h after palmitate exposition and these levels were sustained up to 12h. Palmitate also activated PERK and increased ATF4 expression (respectively after 6 and 12h of treatment). The events were preceded by short-term and transitory AKT activation by palmitate. By inhibiting mTORC1/2 with rapamycin we observed a suppression of palmitate-induced UPR activation and apoptosis. Similarly inhibition of apoptosis and ER stress was also observed with the use of a specific inhibitor for AKT (“AKT inhibitor”) and Rictor knockdown with siRNA.
Conclusion: Our results demonstrated that palmitate induces a short-term and transitory AKT activation that leads to long term activation of UPR and apoptosis. This response is likely to be triggered by mTORC2 activation. All together, those results could help to the understanding of NASH physiopathology.
Nothing to Disclose: TMFD, JDAF, APK, LAV, GFA
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