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Upregulation of rat liver PPARα‐FGF21 signaling by a docosahexaenoic acid and thyroid hormone combined protocol
Author(s) -
Videla Luis A.,
Fernández Virginia,
Vargas Romina,
Cornejo Pamela,
Tapia Gladys,
Varela Nelson,
Valenzuela Rodrigo,
Arenas Allan,
Fernández Javier,
HernándezRodas María C.,
Riquelme Bárbara
Publication year - 2016
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1300
Subject(s) - downregulation and upregulation , fgf21 , hormone , docosahexaenoic acid , thyroid , medicine , endocrinology , deiodinase , peroxisome proliferator activated receptor , chemistry , thyroid hormones , fatty acid , biochemistry , receptor , polyunsaturated fatty acid , gene , fibroblast growth factor
Prevention of ischemia‐reperfusion liver injury is achieved by a combined omega‐3 and thyroid hormone (T 3 ) protocol, which may involve peroxisome‐proliferator activated receptor‐α (PPAR‐α)‐fibroblast growth factor 21 (FGF21) signaling supporting energy requirements. Combined docosahexaenoic acid (DHA; daily doses of 300 mg/kg for 3 days) plus 0.05 mg T 3 /kg given to fed rats elicited higher hepatic DHA contents and serum T 3 levels, increased PPAR‐α mRNA and its DNA binding, with higher mRNA expression of the PPAR‐α target genes for carnitine‐palmitoyl transferase 1α, acyl‐CoA oxidase, and 3‐hydroxyl‐3‐methylglutaryl‐CoA synthase 2, effects that were mimicked by 0.1 mg T 3 /kg given alone or by the PPAR‐α agonist WY‐14632. Under these conditions, the mRNA expression of retinoic X receptor‐α (RXR‐α) is also increased, with concomitant elevation of the hepatic mRNA and protein FGF21 levels and those of serum FGF21. It is concluded that PPAR‐α‐FGF21 induction by DHA combined with T 3 may involve ligand activation of PPAR‐α by DHA and enhanced expression of PPAR‐α by T 3 , with consequent upregulation of the FGF21 that is controlled by PPAR‐α . Considering the beneficial effects of PPAR‐α‐FGF21 signaling on carbohydrate and lipid metabolism, further investigations are required to clarify its potential therapeutic applications in human metabolic disorders. © 2016 BioFactors, 42(6):638–646, 2016