Extended Data Fig. 5: Zfp423 overexpression in PDGFRβ+ cells confers metabolic benefits in obesity.

a) Western blot of phosphorylated AKT (pAKT), total AKT, and β-Actin protein expression in tissue extracts of gonadal WAT from Control (n=3) and Mural-Zfp423^TG (n=3) mice after 5-month HFD feeding. Tissues were collected before (- insulin) and after insulin stimulation (+ insulin).

b) Intraperitoneal glucose tolerance tests (GTT) of thermoneutral-housed Control (n=9) and Mural-Zfp423^TG (n=11) mice after HFD feeding. * denotes p< 0.05 by unpaired two-tailed Student’s t-test.

c) Intraperitoneal insulin tolerance tests (ITT) of thermoneutral-housed Control (n=9) and Mural-Zfp423^TG (n=11) mice after HFD feeding. * denotes p< 0.05 by unpaired two-tailed Student’s t-test.

d) Levels of serum ADIPONECTIN and serum INSULIN (six-hour fasted) in Control and Mural-Zfp423^TG mice maintained on doxycycline-containing chow diet or doxycycline-containing HFD for 1 month or 5 months. For control mice, n=3 of chow, n=9 of 1-month HFD, n=9 of 5-month HFD; for Mural-Zfp423^TG mice, n=3 of chow, n=10 of 1-month HFD, n=7 of 5-month HFD.

e) Serum levels of indicated pro-inflammatory cytokines (CCL2, IL-6, TNFα) in Control (n=8) and Mural-Zfp423^TG (n=8) mice maintained on doxycycline-containing HFD for 5 months.

f) mRNA levels of pro-inflammatory genes in skeletal muscle of Control (n=8) and Mural-Zfp423^TG (n=8) mice after 5-months HFD feeding.

g) mRNA levels of pro-inflammatory genes in livers of Control (n=8) and Mural-Zfp423^TG (n=8) mice after 5-months HFD feeding.

h-j) Levels of total monocytes and pro-inflammatory monocytes (LY6C+) in blood (h), bone marrow (i), and spleen (j) of Control (n=6) and Mural-Zfp423^TG (n=7) mice after 5 months of HFD feeding.

For panels d-j, bars represent mean ± s.e.m., and * denotes p< 0.05 by unpaired two-tailed Student’s t-test. Exact p values, numbers of repetitions, and uncropped western blots can be found in Source Data Extended Data Figure 5.