FoxO1 ablation in adipocytes activates metabolic pathways and improves systemic metabolic health.

(A) Genotyping of FoxO1flox/flox mice and adipoqCreERT2:FoxO1flox/flox mice by PCR and DNA gel imaging. As floxed FoxO1 is located at 149 bp and adipoqCreERT2 at 600 bp, the images indicated that mice #1–2 were of adipoqCreERT2:FoxO1flox/flox and mice #3–4 of FoxO1flox/flox genotype. (B) Western blotting analysis of FoxO1 expression in control and adO1KO mice. Tamoxifen treated FoxO1flox/flox (control, Ctrl) showed normal expression of FoxO1, while tamoxifen-treated adipoqCreERT2:FoxO1flox/flox mice (adO1KO) showed drastic deletion of FoxO1 in white adipose tissue. iBAT, interscapular brown adipose tissues; iWAT inguinal white adipose tissue; gWAT, gonadal white adipose tissue; mWAT, mesenteric white adipose tissue; rWAT, retroperitoneal white adipose tissue. (C–D) adO1KO mice exhibited upregulation of metabolism-regulating genes in gonadal (C) and inguinal (D) adipose tissues. (E–F) KEGG pathway analysis of the upregulated genes in gonadal (E) and inguinal (F) adipose tissues. (G–H) Glucose tolerance test and the area under the curve (n = 6). (I) Insulin tolerance test (n = 8). (J) HOMA-IR indices of the control and adO1KO mice (n = 12). (K–M) Body composition analysis of adO1KO and control mice (n = 8). (N) Measurement of food intake (n = 6). *, p < 0.05; n.s., not significant.