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

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 α (PPARα) by omega-3 polyunsaturated fatty acids and the resulting upregulation of lipid catabolism. However, pharmacological and genetic PPARα manipulations have yielded variable results. We have compared the metabolic effects of FO supplementation and the synthetic PPARα 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.

• Authors: Menghan Liu, Magdalene K Montgomery, Corrine E Fiveash, Brenna Osborne, Gregory J Cooney, Kim Bell-Anderson, Nigel Turner
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 5538 (Jul 02 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24986106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Omega-3
• Fish Oils
• PPAR alpha

Topics

• Adipose Tissue (drug effects, metabolism)
• Adiposity (drug effects)
• Administration, Oral
• Animals
• Dietary Supplements
• Dose-Response Relationship, Drug
• Fatty Acids, Omega-3 (metabolism)
• Fish Oils (administration & dosage, therapeutic use)
• Glucose Intolerance (diet therapy)
• Homeostasis (drug effects, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (diagnosis, diet therapy, metabolism)
• PPAR alpha (metabolism)
• Treatment Outcome