A combined docosahexaenoic acid thyroid hormone protocol upregulates rat liver beta - Klotho expression and downstream components of FGF21 signaling as a potential novel approach to metabolic stress conditions
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Liver preconditioning by a docosahexaenoic acid (DHA) and triiodothyronine (T-3) combined protocol underlies peroxisome-proliferator activated receptor alpha (PPAR alpha)-fibroblast growth factor 21 (FGF21) upregulation, the study of the regulatory mechanisms involved being the aim of this work. Combined DHA (daily doses of 300 mg kg(-1) for 3 days)-T-3 (0.05 mg kg(-1) at the fourth day) administration elicited higher levels of liver DHA and serum T-3, with enhanced hepatic nuclear/cytosolic PPAR alpha ratios, upregulation of FGF21 and beta-Klotho expression, and a small reduction in that of FGF receptor 1 (FGFR1), compared with the respective controls. Concomitantly, the components of the FGF21 cascade extracellular-signal-regulated kinase 1/2 (ERK1/2), FGF receptor substrate 2 alpha (FRS2 alpha), cFos, ribosomal S6 kinase 1 (RSK1), liver kinase B1 (LKB1), and AMP-activated protein kinase (AMPK) were activated. The upregulation of liver PPAR alpha-FGF21-AMPK signaling by the combined DHA-T-3 protocol resulted in values significantly higher than those elicited by the addition of the data obtained for DHA and T-3 alone. It is concluded that combined DHA-T-3 supplementation achieves synergistic effects on liver PPAR alpha-FGF21-AMPK signaling, which may result in significant metabolic changes associated with energy expenditure that are of importance in the treatment of obesity and other metabolic disorders.
FONDECYT, Chile 1150104
Artículo de publicación ISI
Quote ItemFood & Function Vol. 8 (11): 3980-3988