title: 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.affiliation: 1] Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia [2] Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia [3] School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Menghan
authors.initials: M
authors.lastname: Liu
authors.affiliation: 1] Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia [2] Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Magdalene K
authors.initials: MK
authors.lastname: Montgomery
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Corrine E
authors.initials: CE
authors.lastname: Fiveash
authors.affiliation: Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Brenna
authors.initials: B
authors.lastname: Osborne
authors.affiliation: 1] Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia [2] St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cooney
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Bell-Anderson
authors.affiliation: 1] Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia [2] Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Turner
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005395:Fish Oils / Q000008:administration & dosage* / Q000627:therapeutic use; D018149:Glucose Intolerance / Q000178:diet therapy; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000175:diagnosis / Q000178:diet therapy* / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D047493:PPAR alpha