Impact of aging and caloric restriction on fibroblast growth factor 21 signaling in rat white adipose tissue

被引:21
|
作者
Fujii, Namiki [1 ]
Uta, Seira [1 ]
Kobayashi, Masaki [1 ,2 ]
Sato, Tsugumichi [2 ,3 ]
Okita, Naoyuki [2 ,4 ]
Higami, Yoshikazu [1 ,2 ]
机构
[1] Tokyo Univ Sci, Fac Pharmaceut Sci, Lab Mol Pathol & Metab Dis, 2641 Yamazaki, Noda, Chiba 2788510, Japan
[2] Tokyo Univ Sci, Res Inst Sci & Technol, Translat Res Ctr, 2641 Yamazaki, Noda, Chiba 2788510, Japan
[3] Tokyo Univ Sci, Fac Pharmaceut Sci, Lab Drug Informat, 2641 Yamazaki, Noda, Chiba 2788510, Japan
[4] Sanyo Onoda City Univ, Fac Pharmaceut Sci, Div Pathol Biochem, 1-1-1 Daigakudori, Yamaguchi 7560884, Japan
基金
日本学术振兴会;
关键词
Caloric restriction; White adipose tissue; Fibroblast growth factor 21; beta-Klotho; Glucose transporter 1; BETA-KLOTHO; INSULIN-RESISTANCE; METABOLIC-ACTIVITY; FGF21; EXPRESSION; PGC-1-ALPHA; RECEPTOR; OBESITY; PROTEIN-1; FGF-21;
D O I
10.1016/j.exger.2019.01.001
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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-1 alpha. 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.
引用
收藏
页码:55 / 64
页数:10
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