RT Journal Article
SR Electronic
T1 Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 392
OP 400
DO 10.1124/jpet.116.236562
VO 359
IS 3
A1 Li-li Gong
A1 Guang-run Li
A1 Wen Zhang
A1 He Liu
A1 Ya-li Lv
A1 Fei-fei Han
A1 Zi-rui Wan
A1 Ming-biao Shi
A1 Li-hong Liu
YR 2016
UL http://jpet.aspetjournals.org/content/359/3/392.abstract
AB Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)–induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho–mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA–mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.