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

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Liu M, Montgomery MK, Fiveash CE, Osborne B, Cooney GJ, Bell-Anderson K, Turner N

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

Sci Rep. 2014 Jul 2;4:5538. doi: 10.1038/srep05538.

PubMed ID

24986106 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Doconexent	Peroxisome proliferator-activated receptor alpha	Protein	Humans	Yes	Activator	Details
Omega-3 fatty acids	Peroxisome proliferator-activated receptor alpha	Protein	Humans	Unknown	Activator	Details