title: FFAR4 (GPR120) Signaling Is Not Required for Anti-Inflammatory and Insulin-Sensitizing Effects of Omega-3 Fatty Acids.
abstract: Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects ofω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects ofω3-PUFAs remain to be elucidated. In the present study, we usedFfar4knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucroseω3-PUFA; or high fat, high sucroseω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fedω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover,ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated byω3-PUFAs.
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Simone Isling
authors.initials: SI
authors.lastname: Pærregaard
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Agerholm
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Annette Karen
authors.initials: AK
authors.lastname: Serup
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tao
authors.identifier: 0000-0003-2570-9449
authors.initials: T
authors.lastname: Ma
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Lise
authors.identifier: 0000-0003-4468-1947
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China.
authors.forename: Karsten
authors.identifier: 0000-0002-6024-0917
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Benjamin Anderschou Holbech
authors.identifier: 0000-0001-6991-0828
authors.initials: BA
authors.lastname: Jensen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D059305:Diet, High-Fat; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; C498007:FFAR4 protein, mouse; D015525:Fatty Acids, Omega-3; D007328:Insulin; D043562:Receptors, G-Protein-Coupled