Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0802-9064
Article
© Georg Thieme Verlag KG Stuttgart · New York

Metabolomic Analysis of Diet-Induced Obese Mice Supplemented with Eicosapentaenoic Acid

Shigeki Nishitani
1  Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan
,
Atsunori Fukuhara
1  Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan
2  Department of Adipose Management, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan
,
Yasutaka Jinno
3  Research Center, Mochida Pharmaceutical Co., Ltd., 722, Jimba, Gotemba, Shizuoka, Japan
,
Hiroyuki Kawano
3  Research Center, Mochida Pharmaceutical Co., Ltd., 722, Jimba, Gotemba, Shizuoka, Japan
,
Takashi Yano
3  Research Center, Mochida Pharmaceutical Co., Ltd., 722, Jimba, Gotemba, Shizuoka, Japan
,
Michio Otsuki
1  Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan
,
Iichiro Shimomura
1  Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan
› Author Affiliations
Further Information

Publication History

received  14 August 2018
revised  08 November 2018

accepted  20 November 2018

Publication Date:
10 December 2018 (eFirst)

Abstract

Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with anti-inflammatory effects. To determine the effects of EPA on metabolic pathways in obese adipose tissues and liver, mice were fed normal chow diet (NCD), high-fat diet (HFD), or 3% EPA-containing high fat diet (HFD+EPA) for 8 weeks. Metabolomic analysis was performed using epididymal adipose tissues (epi WAT) and liver. Metabolites that were specifically elevated in HFD+EPA, were assessed for their anti-inflammatory properties using RAW264.7 macrophage cells. Body and adipose tissue weights were significantly higher in HFD than NCD, and lower in HFD+EPA than HFD. Plasma insulin levels were significantly higher in HFD than NCD, and lower in HFD+EPA compared with HFD. Plasma monocyte chemotactic protein-1 (MCP-1) levels were higher in HFD than NCD, and tended to be lower in HFD+EPA than HFD. The levels of intermediate metabolites in the glycolytic pathways were lower in HFD compared with NCD and HFD+EPA in both epi WAT and liver, while intermediate metabolites of the TCA cycles were elevated in HFD and HFD+EPA compared with NCD in epi WAT. Among the metabolites in epi WAT, the levels of thiaproline, phenaceturic acid, and pipecolic acid were specifically elevated in HFD+EPA, but not in HFD or NCD. Treatment of RAW264.7 cells with thiaproline significantly ameliorated LPS-induced iNOS expression, while pipecolic acid inhibited LPS-induced IL-1β expression. These results suggest that EPA normalizes glycolytic pathway intermediates in both epi WAT and liver, and induces metabolites with anti-inflammatory properties.

Supplementary material