PMID- 30620889
OWN - NLM
STAT- MEDLINE
DCOM- 20200618
LR  - 20200618
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 118
DP  - 2019 Apr
TI  - Impact of aging and caloric restriction on fibroblast growth factor 21 signaling 
      in rat white adipose tissue.
PG  - 55-64
LID - S0531-5565(18)30595-3 [pii]
LID - 10.1016/j.exger.2019.01.001 [doi]
AB  - Caloric restriction (CR) suppresses age-related pathophysiology and extends 
      lifespan. We recently reported that metabolic remodeling of white adipose tissue 
      (WAT) plays an important role in the beneficial actions of CR; however, the 
      detailed molecular mechanisms of this remodeling remain to be established. In the 
      present study, we aimed to identify CR-induced alterations in the expression of 
      fibroblast growth factor 21 (FGF21), a regulator of lipid and glucose metabolism, 
      and of its downstream signaling mediators in liver and WAT, across the lifespan 
      of rats. We evaluated groups of rats that had been either fed ad libitum or 
      calorie restricted from 3 months of age and were euthanized at 3.5, 9, or 
      24 months of age, under fed and fasted conditions. The expression of FGF21 mRNA 
      and/or protein increased with age in liver and WAT. Interestingly, in the WAT of 
      9-month-old fed rats, CR further upregulated FGF21 expression and eliminated the 
      aging-associated reductions in the expression of FGFR1 and beta-klotho (KLB; 
      FGF21 receptor complex). It also enhanced the expression of FGF21 targets, 
      including glucose transporter 1 and peroxisome proliferator-activated receptor 
      (PPAR)gamma coactivator-1alpha. The analysis of transcriptional regulators of Fgf21 
      suggested that aging and CR might upregulate Fgf21 expression via different 
      mechanisms. In adipocytes in vitro, constitutive FGF21 overexpression upregulated 
      the FGF21 receptor complex and FGF21 targets at the mRNA or protein level. Thus, 
      both aging and CR induced FGF21 expression in rat WAT; however, only CR activated 
      FGF21 signaling. Our results suggest that FGF21 signaling contributes to the 
      CR-induced metabolic remodeling of WAT, likely activating glucose uptake and 
      mitochondrial biogenesis.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Fujii, Namiki
AU  - Fujii N
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 
      278-8510, Japan. Electronic address: 3b16710@ed.tus.ac.jp.
FAU - Uta, Seira
AU  - Uta S
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 
      278-8510, Japan. Electronic address: 3B18508@ed.tus.ac.jp.
FAU - Kobayashi, Masaki
AU  - Kobayashi M
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 
      278-8510, Japan; Translational Research Center, Research Institute of Science and 
      Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, 
      Japan. Electronic address: kobayashim@rs.tus.ac.jp.
FAU - Sato, Tsugumichi
AU  - Sato T
AD  - Translational Research Center, Research Institute of Science and Technology, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; 
      Laboratory of Drug Informatics, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic 
      address: tsugusato@rs.tus.ac.jp.
FAU - Okita, Naoyuki
AU  - Okita N
AD  - Translational Research Center, Research Institute of Science and Technology, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Division 
      of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Sanyo-Onoda 
      City University, 1-1-1 Daigakudori, Sanyo-onoda, Yamaguchi 756-0884, Japan. 
      Electronic address: nokita7@rs.socu.ac.jp.
FAU - Higami, Yoshikazu
AU  - Higami Y
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 
      278-8510, Japan; Translational Research Center, Research Institute of Science and 
      Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, 
      Japan. Electronic address: higami@rs.noda.tus.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190105
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (fibroblast growth factor 21)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipose Tissue, White/*metabolism
MH  - *Aging
MH  - Animals
MH  - *Caloric Restriction
MH  - Fibroblast Growth Factors/blood/*physiology
MH  - Glucose Transporter Type 1/analysis
MH  - Male
MH  - Mice
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - Caloric restriction
OT  - Fibroblast growth factor 21
OT  - Glucose transporter 1
OT  - White adipose tissue
OT  - beta-Klotho
EDAT- 2019/01/09 06:00
MHDA- 2020/06/19 06:00
CRDT- 2019/01/09 06:00
PHST- 2018/09/11 00:00 [received]
PHST- 2018/12/14 00:00 [revised]
PHST- 2019/01/01 00:00 [accepted]
PHST- 2019/01/09 06:00 [pubmed]
PHST- 2020/06/19 06:00 [medline]
PHST- 2019/01/09 06:00 [entrez]
AID - S0531-5565(18)30595-3 [pii]
AID - 10.1016/j.exger.2019.01.001 [doi]
PST - ppublish
SO  - Exp Gerontol. 2019 Apr;118:55-64. doi: 10.1016/j.exger.2019.01.001. Epub 2019 Jan 
      5.