5-aminolevulinate and CHIL3/CHI3L1 treatment amid ischemia aids liver metabolism and reduces ischemia-reperfusion injury.

"data availability statement all sequencing data are available at omix repository ( https://ngdc cncb ac cn/omix/ ) under accession numbers omix002840 omix002841 omix002843. revealed by transcriptomic analysis mouse hir operation ( figure s1 a) also led to complex changes in the expression of genes related to 5-ala metabolism (figures1 b-c and data s1).; prompted by the above results enrichment analysis on the effects of 5-ala on the mouse liver transcriptome after hir was performed (figure 3 a and data s2).; transcriptomic analysis suggested that cx3cr1 deficiency resulted in the repression of complement cascades antigen processing and fatty acid/lipid metabolic activities and facilitated carbohydrate catabolism and cholesterol biosynthesis (figure 4 g-h figure s4 d-g and data s1).; transcriptomic analysis further revealed that the expression of genes enriched in m1 macrophages was downregulated whilst that enriched in m2 macrophages was further augmented in cx3cr1 ko livers6 h after hir (figure 5 c-d figure s5 c and data s1).; from the transcriptomic analysis we noted that the post-hir expression of chil3 also known as ym1 was upregulated in the liver of cx3cr1 ko mice (figure 5 c-d and data s1) chil3 is a lectin secreted by macrophages and considered a m2-specific marker.; transcriptomic and qpcr analyses on cells from these experiments suggested that among the enriched cellular pathways chi3l1 promoted cellular catabolism and lipid metabolism whilst downregulated ribosome biogenesis mitochondrial respiratory electron transport and proton transport in l-02 (figure 6 a-c figure s6 d-g and data s3).; also see data s2 (c) up: oxygen consumption rates (ocr vo 2 ) and respiratory exchange ratio (rer) at annotated conditions; down: average ocr (vo 2 ) and rer at annotated conditions.; also see figure s5 i and data s2 (c) heatmap of degs showing opposite trends between the 5-ala treatment group and the 5-ala + chil3 group versus control (ctrl) (n = 4 per group).; also see figure s5 i and data s2 (d) representative confocal images of bodipy (green) chil3 (magenta) and dapi (blue) fluorescence in mouse liver sections at indicated conditions (scale bar = 10 ? data availability statement all sequencing data are available at omix repository ( https://ngdc cncb ac cn/omix/ ) under accession numbers omix002840"

"Competing Interests: The authors have declared that no competing interest exists."

"We thank Xiaocui Fang for helping with the collection of clinical data. The graphical abstract created with BioRender.com. The heatmap created with hiplot.com.cn. This work was supported by the National Natural Science Foundation of China (82170671, 81972286, 82172585, 82200733), the National Key R&D Plan (2017YFA0104304), the Science and Technology Program of Guangdong Province (2019B020236003), the Science and Technology Program of Guangzhou City (201803040005), the Guangdong Key Laboratory of Liver Disease Research (2020B1212060019) and the Natural Science Foundation of Guangdong Province (2015A030312013)."