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Astragaloside IV attenuates free fatty acid-induced ER stress and lipid
accumulation in hepatocytes via AMPK activation
#MMPMID28344322
Zhou B
; Zhou DL
; Wei XH
; Zhong RY
; Xu J
; Sun L
Acta Pharmacol Sin
2017[Jul]; 38
(7
): 998-1008
PMID28344322
show ga
Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not
completely understood, the increased influx of free fatty acids (FFAs) into the
liver and the FFA-induced hepatic endoplasmic reticulum (ER) stress are two
crucial pathogenic processes in the initiation and development of NAFLD. In this
study we investigated the effects of astragaloside IV (AS-IV), a bioactive
compound purified from Astragali Radix, on FFA-induced lipid accumulation in
hepatocytes and elucidated the underlying mechanisms. Human HepG2 cells and
primary murine hepatocytes were exposed to FFAs (1 mmol/L, oleate/palmitate, 2:1
ratio) with or without AS-IV for 24 h. Exposure to FFAs induced marked lipid
accumulation in hepatocytes, whereas co-treatment with AS-IV (100 ?g/mL)
significantly attenuated this phenomenon. Notably, AS-IV (50-200 ?g/mL)
concentration-dependently enhanced the phosphorylation of AMPK, acetyl-CoA
carboxylase (ACC) and SREBP-1c, inhibited the accumulation and nuclear
translocation of mature SREBP-1 and subsequently decreased the mRNA levels of
lipogenic genes including acc1, fas and scd1. AS-IV treatment also
concentration-dependently attenuated FFA-induced hepatic ER stress evidenced by
the reduction of the key markers, GRP78, CHOP and p-PERK. Pretreated the cells
with the AMPK inhibitor compound C (20 ?mol/L) greatly diminished these
beneficial effects of AS-IV. Our results demonstrate that AS-IV attenuates
FFA-induced ER stress and lipid accumulation in an AMPK-dependent manner in
hepatocytes, which supports its use as promising therapeutics for hepatic
steatosis.
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