IDDF2021-ABS-0207 Type 2 resistant starch improves liver steatosis induced by high-fat diet relating to gut microbiota regulation and concentration of propionic acid in portal vein blood in C57BL/6J mice

Abstract

<h3>Background</h3> Resistant starch (RS) was approved to regulate glucose and lipid metabolism and gut microbiota in vivo. Our aim was to explore the effect and mechanism of type 2 resistant starch (RS2) on NAFLD mice. <h3>Methods</h3> Twenty C57BL/6J male mice were randomly divided into CD group, CD+RS group, HFD group, HFD+RS group (n=5). The NAFLD mouse model was induced by a high-fat diet for 16 weeks. RS2 was supplemented into the diet for 4 weeks subsequently. After treatment, liver steatosis was evaluated by HE staining and NAS score. The serum alanine aminotransferase (ALT), triglyceride (TG), fasting serum glucose (FBG) and insulin resistance index (HOMA-IR) of portal vein blood were detected. The intestinal content of mice was collected for microbiota analysis by 16s amplicon sequencing. The level of short-chain fatty acids (SCFA) in portal vein blood was detected. <h3>Results</h3> Compared with HFD group, after RS intervention, the liver steatosis of mice was significantly reduced, and the serum levels of ALT, TG, FBG and HOMA-IR were significantly decreased (<i>P</i>&lt;0.05) (IDDF2021-ABS-0207 Figure 1a Type 2 resistant starch improves liver steatosis induced by high-fat diet; Hepatic HE staining of mice) (IDDF2021-ABS-0207 Figure 1b Type 2 resistant starch improves liver steatosis induced by high-fat diet; NAS score of mice(**<i>P</i>&lt;0.01)) (IDDF2021-ABS-0207 Figure 1c Type 2 resistant starch improves liver steatosis induced by high-fat diet; Serum levels of ALT in mice (**<i>P</i>&lt;0.01) (IDDF2021-ABS-0207 Figure 1d Type 2 resistant starch improves liver steatosis induced by high-fat diet; Serum levels of TG in mice (**<i>P</i>&lt;0.01, ***<i>P</i>&lt;0.001) (IDDF2021-ABS-0207 Figure 1e Type 2 resistant starch improves liver steatosis induced by high-fat diet; Serum levels of FBG in mice (*<i>P</i>&lt;0.05, ***<i>P</i>&lt;0.001)) (IDDF2021-ABS-0207 Figure 1f Type 2 resistant starch improves liver steatosis induced by high-fat diet; Serum levels of HOMA-IR in mice (**<i>P</i>&lt;0.01, ***<i>P</i>&lt;0.001)). The α diversity of intestinal microflora was decreased in HFD group mice compared with CD group mice, but slightly increased after RS2 intervention (IDDF2021-ABS-0207 Figure 1g Type 2 resistant starch improves liver steatosis induced by high-fat diet; Alpha diversity). LEfSe analysis showed that the abundance of Akkermansia (LDA=6.02) was decreased in the HFD group mice compared with CD group mice and increased significantly after RS2 intervention, indicating that it was a biomarker of NAFLD mice (IDDF2021-ABS-0207 Figure 1h Type 2 resistant starch improves liver steatosis induced by high-fat diet; LEfSe analysis). The concentration of valeric acid in portal vein blood was negatively correlated with the abundance of Akkermansia (r=-0.54, <i>P</i>=0.014), and propionic acid was positively correlated with the abundance of Akkermansia (r=0.47, <i>P</i>=0.036) (IDDF2021-ABS-0207 Figure 1i Type 2 resistant starch improves liver steatosis induced by high-fat diet; Correlation analysis of SCFA and intervention) (IDDF2021-ABS-0207 Figure 1j Type 2 resistant starch improves liver steatosis induced by high-fat diet; Concentration of propanoic acid in portal vein blood. CD, control diet; HFD, high-fat diet; RS, type 2 resistant starch). <h3>Conclusions</h3> RS2 intervention can improve liver steatosis, liver function, serum lipid and serum glucose levels and insulin resistance in NAFLD mice, The α diversity of intestinal microflora in RS2 treated mice was increased too. Akkermansia is a biomarker of NAFLD mice, which is significantly increased after RS2 treatment. The concentration of propionic acid in portal vein blood of mice increased after RS2 treatment and was positively correlated with the abundance of Akkermansia. Diwen Shou and Chuangyu Cao contributed equally to this work.