Fig. 1: Liver-specific knockout of Acox1 protects against high-fat diet-induced obesity, inflammation, and insulin resistance in mice.

a Peroxisomal VLCFA β-oxidation pathway. b Peroxisomal fatty acid β-oxidation gene expression in liver of mice fed with chow or HFD for 16 weeks (n = 3). c Body weight of control and Acox1-LKO male mice fed with HFD (n = 9). d MRI analysis of mice after HFD feeding (n = 9). e Tissue weights of HFD-fed mice; n = 8 (control), n = 9 (Acox1-LKO). f Representative gross images of iWAT from HFD-fed control and Acox1-LKO mice. g H&E staining of adipose tissues from control and Acox1-LKO mice (scale bar, 50 μm). h Cell size quantification in BAT (n = 3 for control, 4 for Acox1-LKO), gWAT (n = 5) and iWAT (n = 3). i Glucose tolerance test of HFD-fed control (n = 9) and Acox1-LKO (n = 11) mice. j–k Serum insulin level (j) and TAG level (k) of control (n = 4) and Acox1-LKO (n = 5) mice. l Akt phosphorylation in livers of mice at baseline and 10 min after insulin injection. Quantification based on n = 4 (basal), 5 (control with insulin) and 6 (LKO with insulin) mice. m Akt phosphorylation in gWAT and iWAT of mice at baseline and 10 min after insulin injection. Quantification based on n = 4/group. n UMAP visualization of CD45+ cells in mice gWAT; ATM, adipose tissue macrophages. o–p Number of macrophages (o) and CD9 + ATM (p) per gram of fat (n = 5). q Density plots of macrophages subpopulation expressing CD11c or CD206 (n = 5). r–s Percentage of CD11c-CD206+ (r) and CD11c + CD206+ (s) in total gWAT macrophages (n = 5). t F4/80 (red) staining in gWAT whole tissue mounts stained with LipidTOX (green) (scale bar, 100 μm). Data in (b–e, h–m, o–p, and r–s) are from biologically independent samples. Images in (f) and (g) are representative of three mice/genotype. Images in (t) are representative of two separate experiments. Data with error bars are reported as the mean ± SEM. P values were determined by two-sided unpaired Student’s t test in (b, d–e, h, j, k, o–p, r, s) or two-way ANOVA followed by Fisher’s LSD test in c, i and l-m. Source data are provided as a Source Data file.