Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1.
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON, Canada, N1G 5C9.
J Nutr Biochem. 2019 Oct;72:108216. doi: 10.1016/j.jnutbio.2019.07.007. Epub 2019 Jul 25.
Impaired intestinal health characterized by a dysbiotic microbial community and a dysfunctional epithelial barrier contributes to host inflammation and metabolic dysfunction in obesity. Fish oil (FO)-derived n-3 polyunsaturated fatty acids have been shown to improve aspects of the obese phenotype; however, their effect on obese intestinal health is unknown. This study aimed to determine the effect of dietary FO on the intestinal microenvironment, including the microbial community and epithelial barrier, in a mouse model of high-fat diet induced obesity and metabolic dysfunction. Male C57BL/6 mice were fed (12 weeks) either a high-fat diet (HF, 60% fat as kcal) or an isocaloric HF supplemented with Menhaden FO (5.3% kcal, HF + FO). 16S rRNA sequencing was used to determine changes in fecal microbiota. Intestinal (ileum and colon) and epididymal adipose tissue RNA was used to assess biomarkers of barrier integrity and inflammatory status, respectively. Serum was used to assess adipokine concentrations and insulin resistance. HF + FO diet altered the fecal microbiota by decreasing the abundance of Firmicutes and increasing the abundance of members of the Bacteroidetes phyla, as well as increasing the abundance of antiobesogenic Akkermansia muciniphila, compared to HF. Intestinal epithelial barrier functions were improved by HF + FO evidenced by increased mRNA expression of tight junction components, antimicrobial defenses and mucus barrier components. HF + FO-fed mice exhibited improvements in homeostatic model assessment of insulin resistance, oral glucose tolerance and serum adipokine concentrations and epididymal mRNA expression (increased adiponectin and decreased leptin) versus HF. HF + FO improved obese intestinal health and attenuated metabolic dysfunction associated with obesity.
肠道健康受损的特征是微生物群落失调和上皮屏障功能障碍，这会导致宿主炎症和肥胖相关的代谢功能障碍。鱼油（FO）衍生的 n-3 多不饱和脂肪酸已被证明可以改善肥胖表型的某些方面；然而，其对肥胖肠道健康的影响尚不清楚。本研究旨在确定膳食 FO 对高脂肪饮食诱导肥胖和代谢功能障碍小鼠模型肠道微环境的影响，包括微生物群落和上皮屏障。雄性 C57BL/6 小鼠喂食（12 周）高脂肪饮食（HF，60%脂肪作为卡路里）或等热量高脂肪饮食补充鲱鱼油（5.3%卡路里，HF+FO）。16S rRNA 测序用于确定粪便微生物群的变化。肠道（回肠和结肠）和附睾脂肪组织 RNA 分别用于评估屏障完整性和炎症状态的生物标志物。血清用于评估脂肪因子浓度和胰岛素抵抗。与 HF 相比，HF+FO 饮食通过降低厚壁菌门的丰度和增加拟杆菌门成员的丰度，以及增加抗肥胖阿克曼菌的丰度，改变了粪便微生物群。与 HF 相比，HF+FO 饮食通过增加紧密连接成分、抗菌防御和粘液屏障成分的 mRNA 表达，改善了肠道上皮屏障功能。与 HF 相比，HF+FO 喂养的小鼠表现出胰岛素抵抗的稳态模型评估、口服葡萄糖耐量和血清脂肪因子浓度以及附睾 mRNA 表达（增加脂联素和减少瘦素）的改善。HF+FO 改善了肥胖的肠道健康，并减轻了与肥胖相关的代谢功能障碍。
