PMID- 33566044
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20210416
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 12
IP  - 5
DP  - 2021 Mar 7
TI  - Plant sterol ester of alpha-linolenic acid ameliorates high-fat diet-induced 
      nonalcoholic fatty liver disease in mice: association with regulating 
      mitochondrial dysfunction and oxidative stress via activating AMPK signaling.
PG  - 2171-2188
LID - 10.1039/d0fo02623a [doi]
AB  - The present study was designed to explore the beneficial mitochondrial effects 
      and anti-oxidative activities of plant sterol ester of alpha-linolenic acid (PS-ALA) 
      through AMP-activated protein kinase (AMPK) signaling in the treatment of 
      nonalcoholic fatty liver disease (NAFLD) using in vivo and in vitro models. The 
      mitochondrial function was evaluated and the oxidative stress index was measured. 
      The protein expression was analyzed by immunohistochemical, immunofluorescence, 
      and western blotting methods. The results showed that PS-ALA significantly 
      suppressed NAFLD and alleviated steatosis in HepG2 cells induced by oleic acid 
      (OA). In addition, PS-ALA promoted mitochondrial biogenesis, enhanced 
      mitochondrial fatty acid oxidation capacity, improved mitochondrial dynamics, and 
      restored mitochondrial membrane potential. Moreover, PS-ALA reduced reactive 
      oxygen species production both in the liver tissue of HFD-fed mice and OA-loaded 
      HepG2 cells. At the molecular level, PS-ALA accelerated the phosphorylation of 
      AMPK and increased the protein expression of peroxisome proliferator-activated 
      receptor-gamma co-activator 1alpha (PGC-1alpha) and nuclear NF-E2-related factor 2 (Nrf2). 
      Furthermore, the stimulating effects of PS-ALA on the PGC-1alpha/Nrf1/Tfam pathway 
      and Nrf2/HO-1 pathway as well as its mitochondrial biogenesis promotion effects 
      and anti-oxidative activities were abrogated by the AMPK inhibitor in OA-treated 
      HepG2 cells. In conclusion, the protective effects of PS-ALA on NAFLD appear to 
      be associated with improving mitochondrial function and oxidative stress via 
      activating AMPK signaling.
FAU - Han, Hao
AU  - Han H
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical 
      University, No. 56, Xinjian South Road, Taiyuan, Shanxi 030001, PR China. 
      hhxx13147799@126.com.
FAU - Li, Xiaoyu
AU  - Li X
FAU - Guo, Yan
AU  - Guo Y
FAU - Zheng, Mingming
AU  - Zheng M
FAU - Xue, Tingli
AU  - Xue T
FAU - Wang, Linqi
AU  - Wang L
LA  - eng
PT  - Journal Article
DEP - 20210210
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Esters)
RN  - 0 (Phytosterols)
RN  - 0 (Reactive Oxygen Species)
RN  - 0RBV727H71 (alpha-Linolenic Acid)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Diet, High-Fat
MH  - Enzyme Activation/drug effects
MH  - Esters/chemistry/*therapeutic use
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver/chemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria, Liver/drug effects/physiology/ultrastructure
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/physiopathology
MH  - Oxidative Stress/*drug effects
MH  - Phosphorylation
MH  - Phytosterols/chemistry/*therapeutic use
MH  - Reactive Oxygen Species/analysis
MH  - Signal Transduction/drug effects
MH  - alpha-Linolenic Acid/*chemistry
EDAT- 2021/02/11 06:00
MHDA- 2021/04/17 06:00
CRDT- 2021/02/10 12:10
PHST- 2021/02/11 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2021/02/10 12:10 [entrez]
AID - 10.1039/d0fo02623a [doi]
PST - ppublish
SO  - Food Funct. 2021 Mar 7;12(5):2171-2188. doi: 10.1039/d0fo02623a. Epub 2021 Feb 
      10.