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. 2021 Oct 1;43(6):518–533. doi: 10.1093/eurheartj/ehab644

Figure 5.

Figure 5

Regulation of Npc1l1 gene expression by interleukin-10 mediates propionate-dependent control of intestinal cholesterol absorption and atheroprotection. (A) Representative photomicrograph of a mouse small intestinal epithelial organoid. (B) The organoids express both the interleukin-10R1 and interleukin-10R2 receptors, as demonstrated by reverse transcription-polymerase chain reaction. (C) Treatment of the organoids with murine recombinant interleukin-10 down-regulated the expression of the Npc1l1 gene in a dose-dependent manner (n = 4 independent biological replicates). (D) Interleukin-10 signalling was inhibited by weekly i.p. injection of a monoclonal blocking antibody against the interleukin-10 receptor in high-fat diet-fed Apoe−/− mice during the propionic acid treatment period (high-fat diet + propionic acid n = 13, high-fat diet + propionic acid + interleukin-10R antibody n = 8). (E–H) HPLC analysis of blood levels of total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in high-fat diet + propionic acid mice in the presence (grey) or absence (blue) of interleukin-10R antibody. (I) Representative HPLC-assisted fractionation of plasma lipids. (J and K) Representative images of Oil Red O-stained aortic root sections (scale bars represent 100 µm) with quantification of lipid deposition (high-fat diet + propionic acid n = 11, high-fat diet + propionic acid + interleukin-10R antibody n = 7). (L and M) Analysis of blood levels of the phytosterols stigmasterol and sitosterol at the end of the experiments (high-fat diet + propionic acid n = 13, high-fat diet + propionic acid + interleukin-10R antibody n = 8). For the analysis in E–M, the results for the high-fat diet + propionic acid group were the same results used in Figure 2. Data were analysed by a two-tailed unpaired t-test. HDL, high-density lipoprotein; HFD, high-fat diet; LDL, low-density lipoprotein; IL-10, interleukin-10; PA, propionic acid; VLDL, very low-density lipoprotein.