PMID- 33310031
OWN - NLM
STAT- MEDLINE
DCOM- 20210201
LR  - 20210201
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 266
DP  - 2021 Feb 1
TI  - WY14643 improves left ventricular myocardial mitochondrial and systolic functions 
      in obese rats under chronic persistent hypoxia via the PPARalpha pathway.
PG  - 118888
LID - S0024-3205(20)31641-6 [pii]
LID - 10.1016/j.lfs.2020.118888 [doi]
AB  - AIMS: Peroxisome proliferator-activated receptor (PPAR) alpha, a key regulator of 
      lipid metabolism, plays a role in maintaining the homeostasis of myocardial 
      energy metabolism. Both hypoxia and obesity inhibit the expression of PPARalpha in 
      the myocardium. In this study, we verified the inhibitory effects of hypoxia and 
      obesity on PPARalpha and examined whether WY14643 
      (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid), an agonist of PPARalpha, 
      ameliorates myocardial mitochondrial dysfunction and protects cardiac function in 
      obese rats under chronic persistent hypoxia. MAIN METHODS: Sprague-Dawley rats 
      were randomly divided into six groups: a control group (normal chow diet, normal 
      oxygen), a high-fat diet (HFD) group (normal oxygen), a chronic persistent 
      hypoxia normal chow diet group, a chronic persistent hypoxia HFD group, a chronic 
      persistent hypoxia HFD group with WY14643 treatment, and a chronic persistent 
      hypoxia HFD group with vehicle treatment. KEY FINDINGS: Hypoxia and obesity 
      increased myocardial lipid accumulation, mitochondrial dysfunction, and left 
      ventricular systolic dysfunction. Myocardial lipid metabolism-related genes, 
      including those encoding PPARalpha, PPARgamma coactivator 1alpha (PGC1alpha), and carnitine 
      palmitoyl transferase 1alpha (CPT1alpha), were downregulated, while acetyl-CoA 
      carboxylase 2 (ACC2) was upregulated under a combination of hypoxia and obesity. 
      WY14643 upregulated PPARalpha, PGC1alpha, and CPT1alpha, and downregulated ACC2. WY14643 
      alleviated hypoxia- and obesity-induced myocardial lipid accumulation and 
      improved mitochondrial and left ventricular systolic functions. SIGNIFICANCE: 
      WY14643 improved myocardial mitochondrial and left ventricular systolic functions 
      in obese rats under chronic persistent hypoxia. Thus, WY14643 possibly exerts its 
      effects by regulating the PPARalpha pathway and shows potential as a therapeutic 
      target for cardiovascular diseases associated with obesity and hypoxia.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Yan, Jun
AU  - Yan J
AD  - Research Center for High Altitude Medicine, Qinghai University Medical College, 
      Xining 810001, PR China; Key Laboratory of Persistent medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of Persistent Medicine in Qinghai Province, Xining 810001, PR China; 
      Cardiovascular Medicine Department, Xuzhou Medical University affiliated 
      hospital, Xuzhou 221006, PR China.
FAU - Song, Kang
AU  - Song K
AD  - Endocrinology Department, Qinghai Provincial People's Hospital, Xining 810000, 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 Persistent medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of Persistent Medicine in Qinghai Province, Xining 810001, PR China.
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 Persistent medicine (Qinghai 
      University), Ministry of Education, Xining 810001, PR China; Key Laboratory for 
      Application of Persistent Medicine in Qinghai Province, Xining 810001, PR China. 
      Electronic address: geriligao@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20201210
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (PPAR alpha)
RN  - 0 (Pyrimidines)
SB  - IM
MH  - Animals
MH  - Hypoxia/*physiopathology
MH  - Male
MH  - Mitochondria, Heart/*drug effects/metabolism/pathology
MH  - Obesity/*physiopathology
MH  - PPAR alpha/*agonists
MH  - Pyrimidines/chemistry/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke Volume
MH  - Systole/*drug effects
MH  - Ventricular Dysfunction, Left/*drug therapy/etiology/pathology
OTO - NOTNLM
OT  - Chronic hypoxia
OT  - Left ventricular systolic function
OT  - Mitochondria
OT  - Obesity
OT  - PPARalpha
OT  - WY14643
EDAT- 2020/12/15 06:00
MHDA- 2021/02/02 06:00
CRDT- 2020/12/14 10:19
PHST- 2020/09/09 00:00 [received]
PHST- 2020/12/04 00:00 [revised]
PHST- 2020/12/04 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/02/02 06:00 [medline]
PHST- 2020/12/14 10:19 [entrez]
AID - S0024-3205(20)31641-6 [pii]
AID - 10.1016/j.lfs.2020.118888 [doi]
PST - ppublish
SO  - Life Sci. 2021 Feb 1;266:118888. doi: 10.1016/j.lfs.2020.118888. Epub 2020 Dec 
      10.