Abstract
Scope:
To assess the individual effects of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin resistance (IR), gut microbiome and gut metabolites in high-fat diet-induced obese (DIO) mice.
Methods and results:
DIO mice were fed an either high-fat diet (HFD), EPA (1% wt/wt) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplementation reversed hyperglycemia and IR but did not affect body weight in DIO mice while DHA exhibited a more pronounced ameliorative effect in male mice. Both EPA and DHA enriched Lactobacillus and short-chain fatty acids (SCFAs)-producing species from Lachnospiraceae while reduced lipopolysaccharide (LPS)-producing Bilophila and Escherichia/Shigella. Compared with EPA, DHA supplemented mice had more abundant propionic/butyric acid-producing bacteria, including Coprococcus, Butyricimonas synergistica, Bacteroides acidifaciens, and Intestinimonas, and less abundant LPS-correlated species Streptococcus and p-75-a5. The shifts in gut microbiome co-occurred with the changes in levels of propionic/butyric acid, circulating LPS and serotonin. Additionally, EPA/DHA supplementation attenuated adipose inflammation with upregulated GLUT4 and Akt phosphorylation, indicating the improvement of insulin signaling.
Conclusions:
EPA and DHA differentially reversed IR and relieved adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut-adipose axis as a primary target of EPA/DHA. This article is protected by copyright. All rights reserved.
Full text
