PMID- 32289432
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 252
DP  - 2020 Jul 1
TI  - High-altitude chronic hypoxia ameliorates obesity-induced non-alcoholic fatty 
      liver disease in mice by regulating mitochondrial and AMPK signaling.
PG  - 117633
LID - S0024-3205(20)30381-7 [pii]
LID - 10.1016/j.lfs.2020.117633 [doi]
AB  - AIMS: High-fat intake induces obesity and non-alcoholic fatty liver disease 
      (NAFLD). However, high-altitude chronic hypoxia might alleviate NAFLD progression 
      through improved mitochondrial function and AMP-activated protein kinase (AMPK) 
      signaling. We hypothesized that high-altitude chronic hypoxia would have 
      protective effects against NAFLD development. MAIN METHODS: C57BL/6J mice were 
      randomly divided into control (normal diet and altitude 50 m), CHH (normal diet 
      and altitude 4300 m), HFD (high-fat diet and altitude 50 m), and HFD-CHH 
      (high-fat diet and altitude 4300 m) groups. After being maintained for 8 weeks 
      under the appropriate conditions, mice were evaluated. KEY FINDINGS: The degree 
      of liver lipid accumulation and expression of the lipid synthesis-related genes 
      acetyl-CoA carboxylase1 (ACC1), fatty acid synthesis (FAS), and sterol regulatory 
      element binding protein-1c (SREBP-1c) were reduced in the HFD-CHH group; however, 
      expression of the lipolysis-related gene carnitine palmitoyl transferase 1 (CPT1) 
      was increased. Furthermore, in addition to increased expression of mitochondrial 
      biogenesis-related genes, mitochondrial respiratory function and mitochondrial 
      DNA content were elevated in the HFD-CHH group compared to those in the HFD 
      group. The HFD-CHH group also exhibited significantly increased antioxidation 
      activity and decreased reactive oxygen species production (P < 0.05). Finally, 
      AMPK signaling in the liver was activated and the expression of 
      phosphorylated-AMPK (P-AMPK) was significantly increased in the HFD-CHH group. 
      SIGNIFICANCE: Collectively, our findings suggest that high altitude-induced 
      hypoxia might improve impaired mitochondrial function and activate AMPK signaling 
      in obesity-induced NAFLD. High-altitude chronic hypoxia could be a new treatment 
      strategy for obesity-induced NAFLD.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Song, Kang
AU  - Song K
AD  - Research Center for High Altitude Medicine, Qinghai University Medical College, 
      Xining 810001, PR China; Key Laboratory of High Altitude Medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of High Altitude Medicine in Qinghai Province, Xining 810001, PR 
      China; Endocrinology Department, Qinghai Provincial People's Hospital, Xining 
      810000, PR China.
FAU - Zhang, Yifan
AU  - Zhang Y
AD  - Research Center for High Altitude Medicine, Qinghai University Medical College, 
      Xining 810001, PR China; Key Laboratory of High Altitude Medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of High Altitude Medicine in Qinghai Province, Xining 810001, PR 
      China.
FAU - Ga, Qin
AU  - Ga Q
AD  - Research Center for High Altitude Medicine, Qinghai University Medical College, 
      Xining 810001, PR China; Key Laboratory of High Altitude Medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of High Altitude Medicine in Qinghai Province, Xining 810001, PR 
      China.
FAU - Bai, Zhenzhong
AU  - Bai Z
AD  - Research Center for High Altitude Medicine, Qinghai University Medical College, 
      Xining 810001, PR China; Key Laboratory of High Altitude Medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of High Altitude Medicine in Qinghai Province, Xining 810001, PR 
      China. Electronic address: baizz@126.com.
FAU - Ge, Ri-Li
AU  - Ge RL
AD  - Research Center for High Altitude Medicine, Qinghai University Medical College, 
      Xining 810001, PR China; Key Laboratory of High Altitude Medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of High Altitude Medicine in Qinghai Province, Xining 810001, PR 
      China. Electronic address: geriligao@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20200411
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (DNA, Mitochondrial)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Altitude
MH  - Animals
MH  - DNA, Mitochondrial/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Disease Progression
MH  - Hypoxia/*metabolism
MH  - Lipid Metabolism/physiology
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*metabolism
MH  - Non-alcoholic Fatty Liver Disease/etiology/*therapy
MH  - Obesity/*complications
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - AMPK
OT  - Chronic hypoxia
OT  - High altitude
OT  - Mitochondria
OT  - NAFLD
OT  - Obesity
COIS- Declaration of competing interest The authors declare no conflicts of interest.
EDAT- 2020/04/15 06:00
MHDA- 2020/06/02 06:00
CRDT- 2020/04/15 06:00
PHST- 2019/12/03 00:00 [received]
PHST- 2020/03/27 00:00 [revised]
PHST- 2020/03/31 00:00 [accepted]
PHST- 2020/04/15 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2020/04/15 06:00 [entrez]
AID - S0024-3205(20)30381-7 [pii]
AID - 10.1016/j.lfs.2020.117633 [doi]
PST - ppublish
SO  - Life Sci. 2020 Jul 1;252:117633. doi: 10.1016/j.lfs.2020.117633. Epub 2020 Apr 
      11.