Fig. 3: ANGPTL8 promotes MDM migration and activation.

a Pathway enrichment analysis in MDMs treated with rA8. b Representative western blot for intracellular ANGPTL8 protein expression in different mouse tissues. Uncropped blots are provided in Source Data. c Flow cytometry analysis of KCs (CLEC2^hi F4/80^hi CD11b^lo) and MDMs (CLEC2^lo CD11b^hi F4/80^lo) in Alb-Cre, loxp/loxp, and Angptl8^HepKO mice. d Liver macrophage, KC, and MDM quantification in loxp/loxp and Angptl8^HepKO mice after KC deletion with clodronate liposomes (0, 1, 3, 7, 10 days) (n = 3 or 4 mice/group). e Experimental scheme to develop bone marrow (BM) chimeras using loxp and Angptl8^HepKO cells as recipients and congenic mTmG cells as donors (n = 10 or 11). f Representative images showing tdTomato+ cells in liver sections as well as quantification. g Flow cytometry analysis of KCs (CLEC2^hi F4/80^hi CD11b^lo) and MDMs (CLEC2^lo CD11b^hi F4/80^lo) in the livers of Angptl8^HepKO mice after rA8 injection (n = 7 or 9 mice/group). h Quantification of MDM migration to rA8 over time (n = 3 independent experiments). i Flow cytometry of MDM polarization after treatment with Scramble (blue), rA8 (red), and LPS (orange). j RNA sequence showing changes in M1/M2 markers of MDMs after rA8 stimulation. k Hepatocytes were cocultured with MDMs and treated with rA8 and PA, after which they were stained for lipid droplets (Oil Red O; scale bar, 100 µm) and apoptosis (TUNEL, highlighted by yellow arrow; scale bar, 200 µm). The data are shown as the mean ± s.e.m. and were statistically analyzed by one-way ANOVA with Tukey’s multiple-comparison test (g) or two-tailed Student’s t-test (d, f, h). All the p values were two-sided and adjustments were made for multiple comparisons. Data shown are representative of two (b) or four (k) independent experiments with similar results. n indicates the number of biologically independent samples examined. kD relative molecular weight in kilodalton, ND normal diet, CDHFD choline-deficient high-fat diet, eWAT epididymal white adipose tissue, iWAT inguinal white adipose tissue, rA8 recombinant ANGPTL8 protein, KCs Kupffer cells, MDMs monocyte-derived macrophages, PA palmitate. Source data are available as a Source Data file.