PT  - JOURNAL ARTICLE
AU  - Li-li Gong
AU  - Guang-run Li
AU  - Wen Zhang
AU  - He Liu
AU  - Ya-li Lv
AU  - Fei-fei Han
AU  - Zi-Rui Wan
AU  - Ming-Biao Shi
AU  - Li-hong Liu
TI  - Akebia saponin D decreases hepatic steatosis through autophagy modulation
AID  - 10.1124/jpet.116.236562
DP  - 2016 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.116.236562
4099  - http://jpet.aspetjournals.org/content/early/2016/09/23/jpet.116.236562.short
4100  - http://jpet.aspetjournals.org/content/early/2016/09/23/jpet.116.236562.full
AB  - Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing. However, there is a lack of appropriate drugs for the therapy of NAFLD. In the present article, we aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD on ob/ob mice and BRL cells. ASD significantly decreased hepatic steatosis and heptocyte apoptosis in ob/ob mice. Furthermore, ASD significantly activated the autophagic flux assessed by decreased the expression of LC3-II, p62 accumulation of autophagosomes. In BRL cells, ASD prevented OA induced lipid droplets and increase the autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA induced LC3-II, p62, Beclin and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not prevent the OA increased autophagy related protein expression after treated with CQ or siRNA-mediated knockdown of Atg7. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, autophagy modulation via ASD may offer a new strategy for treating NAFLD.