Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation.
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.
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China hongllh@126.com.
Li-Li
LL
Gong
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Guang-Run
GR
Li
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Wen
W
Zhang
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
He
H
Liu
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Ya-Li
YL
Lv
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Fei-Fei
FF
Han
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Zi-Rui
ZR
Wan
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Ming-Biao
MB
Shi
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Li-Hong
LH
Liu
D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D020738:Leptin / Q000172:deficiency; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use
D020738:Leptin; D008055:Lipids; D012503:Saponins; C534004:akebia saponin D