Fig. 4: Impaired BAT function in p62flx/flx Ucp1-Cre mice.
From: The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation
Expression of p62 in BAT of p62flx/flx Ucp1-Cre negative (Cre−) or p62flx/flx Ucp1-Cre positive (Cre+) mice (a), infrared thermographic imaging in female and male mice (b) and surface temperature (c) of 7-d-old p62flx/flx Ucp1-Cre− or p62flx/flx Ucp1-Cre+ mice. Body weight (d), body weight change (e), and cumulative food intake (f) of HFD-fed p62flx/flx male Ucp1-Cre− or p62flx/flx Ucp1-Cre+ mice. Gene expression of Ucp1 (g), Pgc-1α (h) and Cidea (i) and isoproterenol-induction of Ucp1 mRNA expression (j) in BAT primary cells harvested from 6- to 8-wk-old male p62flx/flx Ucp1-Cre− or p62flx/flx Ucp1-Cre+ mice, during 6 d of differentiation. Sample sizes are (a) n = 6/8 mice, (b) n = 3/5 mice, (c–e) n = 7/8 mice. f cumulative food intake was assessed per cage in n = 4/4 cages containing n = 7/8 mice; 2 cages (n = 1/1) were excluded because mice shredded food. g–i BAT primary cells were harvested from p62 wt or Ucp1-cre p62flx/flx mice, plated with equal number of cells in n = 3 wells each genotype and individually differentiated into mature brown adipocytes. Target gene expression was then measured in n = 3 individually differentiated wells each genotype with two technical replicates each well. j BAT primary cells were harvested from p62 wt or Ucp1-cre p62flx/flx mice, plated with equal number of cells in n = 3 wells each treatment group and individually differentiated into mature brown adipocytes. Target gene expression was then measured in n = 3 individually differentiated wells each treatment group with two technical replicates each well. Data in (d–i) are analyzed using two-way ANOVA using time and genotype as covariate and using Bonferroni post hoc multiple comparison to test for differences in individual time points. Data in (a), (c), and (j) were analyzed using two-sided two-tailed t-test. Data represent mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001; ****P < 0.0001. Exact p-values are (a) p = 0.000424; (c) p = 0.0428; (d) d23 p = 0.0286, d24 p = 0.0082, d25 p = 0.0070, d26 p = 0.150; (e) d22 p = 0.0019, d23 p = 0.0006, d24 p = 0.0004, d25 p = 0.0009; (g) d4 p < 0.0001, d6 p < 0.0001; (h) d4 p = 0.0011, d6 p = 0.037; (i) d4 p = 0.0015, d6 p < 0.00; (j) p = 0.0116.
