Free Fatty Acid Receptor 4 Mediates the Beneficial Effects of n-3 Fatty Acids on Body Composition in Mice

• Published in: Calcified tissue international Vol. 101; no. 6; pp. 654 - 662
• Main Authors: Cho, Han Jin, Ahn, Seong Hee, Lee, Young-Sun, Lee, Seung Hun, Im, Dong-Soon, Kim, Inki, Koh, Jung-Min, Kim, Sungsub, Kim, Beom-Jun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2017; Springer Nature B.V
• Subjects: Animal models; Animals; Biochemistry; Biomedical and Life Sciences; Body composition; Body Composition - physiology; Body fat; Cell Biology; Diet, High-Fat; Endocrinology; Fatty acids; Fatty Acids, Omega-3 - metabolism; Female; Life Sciences; Male; Medical importance; Mice; Mice, Knockout; Mice, Transgenic; Obesity; Original Research; Orthopedics; Ovariectomy; Receptors, G-Protein-Coupled - metabolism; Rodents; Sarcopenic obesity; n-3 fatty acids; Free fatty acid receptor 4; Fat-1; Body composition
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-017-0323-y

As populations continue to age worldwide, sarcopenic obesity has heightened interest due to its medical importance. Although much evidence now indicates that n-3 fatty acids (FAs) may have beneficial effects on body composition including fat and muscle, their exact mechanisms have not yet been elucidated. Because free FA receptor 4 (FFA4) has been reported to be a receptor for n-3 FAs, we hypothesized that the protective role of n-3 FAs on body composition could be mediated by FFA4. To test this possibility, we generated mice overexpressing n-3 FAs but lacking FFA4 by crossing fat - 1 transgenic ( fat - 1 Tg+ ) and FFA4 knockout ( Ffar4 −/− ) mice. Because fat - 1 Tg+ mice, in which n-6 is endogenously converted into n-3 FAs, contain high n-3 FA levels, they could be a good animal model for studying the effects of n-3 FAs in vivo. Male and female littermates were included in high-fat-diet- (HFD) and ovariectomy-induced models, respectively. In the HFD model, male fat - 1 Tg+ mice had a lower percentage of fat mass and a higher percentage of lean mass than their wild-type littermates only when they had the Ffar4 +/+ not the Ffar4 −/− background. Female fat - 1 Tg+ mice showed less increase of fat mass percentage and less decrease of lean mass percentage after ovariectomy than wild-type littermates. However, these effects on body composition were attenuated in the Ffar4 −/− background. Taken together, our results indicate that the beneficial effects of n-3 FAs on body composition were mediated by FFA4 and thus suggest that FFA4 may be a potential therapeutic target for modulating sarcopenic obesity.