PMID- 32954538
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210427
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 11
DP  - 2020 Nov
TI  - Time-restricted feeding alleviates cardiac dysfunction induced by simulated 
      microgravity via restoring cardiac FGF21 signaling.
PG  - 15180-15196
LID - 10.1096/fj.202001246RR [doi]
AB  - Dietary restriction has been well-described to improve health metrics, but 
      whether it could benefit pathophysiological adaptation to extreme environment, 
      for example, microgravity, remains unknown. Here, we investigated the effects of 
      a daily rhythm of fasting and feeding without reducing caloric intake on cardiac 
      function and metabolism against simulated microgravity. Male rats under ad 
      libitum feeding or time-restricted feeding (TRF; food access limited to 8 hours 
      every day) were subjected to hindlimb unloading (HU) to simulate microgravity. HU 
      for 6 weeks led to left ventricular dyssynchrony and declined cardiac function. 
      HU also lowered pyruvate dehydrogenase (PDH) activity and impaired glucose 
      utilization in the heart. All these were largely preserved by TRF. TRF showed no 
      effects on HU-induced loss of cardiac mass, but significantly improved 
      contractile function of cardiomyocytes. Interestingly, TRF raised liver-derived 
      fibroblast growth factor 21 (FGF21) level and enhanced cardiac FGF21 signaling as 
      manifested by upregulation of FGF receptor-1 (FGFR1) expression and its 
      downstream markers in HU rats. In isolated cardiomyocytes, FGF21 treatment 
      improved PDH activity and glucose utilization, consequently enhancing cell 
      contractile function. Finally, both liver-specific knockdown (KD) of FGF21 and 
      cardiac-specific FGFR1 KD abrogated the cardioprotective effects of TRF in HU 
      rats. These data demonstrate that TRF improves cardiac glucose utilization and 
      ameliorates cardiac dysfunction induced by simulated microgravity, at least 
      partially, through restoring cardiac FGF21 signaling, suggesting TRF as a 
      potential countermeasure for cardioprotection in long-term spaceflight.
CI  - (c) 2020 Federation of American Societies for Experimental Biology.
FAU - Wang, Xin-Pei
AU  - Wang XP
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Xing, Chang-Yang
AU  - Xing CY
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
AD  - Department of Ultrasound Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, China.
FAU - Zhang, Jia-Xin
AU  - Zhang JX
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Zhou, Jia-Heng
AU  - Zhou JH
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Li, Yun-Chu
AU  - Li YC
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Yang, Hong-Yan
AU  - Yang HY
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Zhang, Peng-Fei
AU  - Zhang PF
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Huang, Yin
AU  - Huang Y
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance, China 
      Pharmaceutical University, Nanjing, China.
FAU - Long, Jian-Gang
AU  - Long JG
AD  - Center for Mitochondrial Biology and Medicine, Center for Translational Medicine, 
      School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
FAU - Gao, Feng
AU  - Gao F
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Zhang, Xing
AU  - Zhang X
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
FAU - Li, Jia
AU  - Li J
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200921
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (fibroblast growth factor 21)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Animals
MH  - *Energy Intake
MH  - *Fasting
MH  - Fibroblast Growth Factors/genetics/*metabolism
MH  - Heart Diseases/etiology/metabolism/pathology/*prevention & control
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Weightlessness Simulation/*adverse effects
OTO - NOTNLM
OT  - FGF21
OT  - cardiac function
OT  - diet
OT  - glucose utilization
OT  - microgravity
EDAT- 2020/09/22 06:00
MHDA- 2021/04/28 06:00
CRDT- 2020/09/21 06:28
PHST- 2020/05/17 00:00 [received]
PHST- 2020/08/28 00:00 [revised]
PHST- 2020/09/03 00:00 [accepted]
PHST- 2020/09/22 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/09/21 06:28 [entrez]
AID - 10.1096/fj.202001246RR [doi]
PST - ppublish
SO  - FASEB J. 2020 Nov;34(11):15180-15196. doi: 10.1096/fj.202001246RR. Epub 2020 Sep 
      21.