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PPARalpha-independent actions of omega-3 PUFAs contribute to their beneficial effects on adiposity and glucose homeostasis


Excess dietary lipid generally leads to fat deposition and impaired glucose homeostasis, but consumption of fish oil (FO) alleviates many of these detrimental effects. The beneficial effects of FO are thought to be mediated largely via activation of the nuclear receptor peroxisomal-proliferator-activated receptor alpha (PPARalpha) by omega-3 polyunsaturated fatty acids and the resulting upregulation of lipid catabolism. However, pharmacological and genetic PPARalpha manipulations have yielded variable results. We have compared the metabolic effects of FO supplementation and the synthetic PPARalpha agonist Wy-14,643 (WY) in mice fed a lard-based high-fat diet. In contrast to FO, WY treatment resulted in little protection against diet-induced obesity and glucose intolerance, despite upregulating many lipid metabolic pathways. These differences were likely due to differential effects on hepatic lipid synthesis, with FO decreasing and WY amplifying hepatic lipid accumulation. Our results highlight that the beneficial metabolic effects of FO are likely mediated through multiple independent pathways.

Type Journal
ISBN 2045-2322 (Electronic) 2045-2322 (Linking)
Authors Liu, M. ; Montgomery, M. K. ; Fiveash, C. E. ; Osborne, B. ; Cooney, G. J. ; Bell-Anderson, K. ; Turner, N.;
Publisher Name Scientific Reports
Published Date 2014-01-01
Published Volume 4
Published Pages 5538
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version