Pan Zhuang1, Yu Zhang1, Qiyang Shou2, Haoyu Li1, Ya'er Zhu3, Lilin He1, Jingnan Chen1, Jingjing Jiao4. 1. Zhejiang Key Laboratory for Agro-Food Processing, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, 310058, China. 2. The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, China. 3. Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China. 4. Department of Nutrition, School of Public Health, Department of Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
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 are fed an either high-fat diet (HFD), EPA (1% w/w) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplements reverse hyperglycemia and IR but do not affect body weight in DIO mice while DHA exhibits 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 have 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 attenuates adipose inflammation with upregulated glucose transporter 4 and Akt phosphorylation, indicating the improvement of insulin signaling. CONCLUSION: EPA and DHA differentially reverse IR and relieve adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut-adipose axis as a primary target of EPA/DHA.
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 are fed an either high-fat diet (HFD), EPA (1% w/w) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplements reverse hyperglycemia and IR but do not affect body weight in DIO mice while DHA exhibits 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 have 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 attenuates adipose inflammation with upregulated glucose transporter 4 and Akt phosphorylation, indicating the improvement of insulin signaling. CONCLUSION:EPA and DHA differentially reverse IR and relieve adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut-adipose axis as a primary target of EPA/DHA.