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Calcif Tissue Int. 2017 Dec;101(6):654-662. doi: 10.1007/s00223-017-0323-y. Epub 2017 Sep 12.

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

Author information

1
Asan Medical Center, Asan Institute for Life Sciences, Seoul, 05505, South Korea.
2
Department of Endocrinology and Metabolism, Inha University Hospital, Inha University School of Medicine, Inchon, 22332, South Korea.
3
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
4
Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Pusan, 46241, South Korea.
5
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
6
Graduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Taejon, 34134, South Korea. sungsub@cnu.ac.kr.
7
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea. umkbj@naver.com.

Abstract

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.

KEYWORDS:

Body composition; Fat-1; Free fatty acid receptor 4; Sarcopenic obesity; n-3 fatty acids

PMID:
28900676
DOI:
10.1007/s00223-017-0323-y
[Indexed for MEDLINE]

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