Cold tolerance test of male UCP1 KO mice and DKO mice (UCP1 KO × C4orf3 CRISPRi). The mice were chronically treated with the β3-adrenergic receptor agonist CL316,243 for 5 days to stimulate beige fat biogenesis in both groups. n= 8 per group. Statistic: two-way ANOVA with Sidak's multiple comparisons test and individual unpaired t tests.