Michio Otsuki    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor and Division head
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Metabolomic Analysis of Diet-Induced Obese Mice Supplemented with Eicosapentaenoic Acid
Journal	Formal name：Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association Abbreviation：Exp Clin Endocrinol Diabetes ISSN code：09477349/14393646
Domestic / Foregin	Foregin
Volume, Issue, Page	128(8),pp.548-555
Author and coauthor	Nishitani, S. Fukuhara, A. Jinno, Y. Kawano, H. Yano, T. Otsuki, M. Shimomura, I.
Publication date	2020
Summary	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-1beta expression. These results suggest that EPA normalizes glycolytic pathway intermediates in both epi WAT and liver, and induces metabolites with anti-inflammatory properties.
DOI	10.1055/a-0802-9064
Document No.	30536265