ERRs Act Collectively and in a Redundant Manner to Promote BAT Mitochondrial Oxidative Capacity
(A) Relative ERR mRNA levels in BAT from WT or littermate mice with adipose-specific deletions of ERRα (ERRαAd−/−), ERRβ and ERRγ (ERRβγAd−/−), or ERRα and ERRγ (ERRαγAd−/−), expressed relative to the levels of each gene in WT BAT and normalized to Ppia. Numbers above bars represent Ct (threshold cycle) values for each ERR isoform in WT BAT.
(B) Western blot of ERRα, ERRγ, and RAN (ras-related nuclear protein; loading control).
(C) Relative mRNA levels of genes acting in the tricarboxylic acid (TCA) cycle and/or oxidative phosphorylation (OxPhos) and normalized to Ppia.
(D) Representative western blot of OxPhos complexes I–V and RAN (loading control) protein.
(E) Quantification of OxPhos complexes, based on blots of panel D (expressed relative to levels in WT BAT and normalized to RAN protein).
(F) Relative mitochondrial DNA (mtDNA) copy number, normalized to gDNA in BAT of the same mice.
(A–F) Mice were born and raised at thermoneutrality (30°C) and euthanized at 12 weeks of age. Data are mean ± SD of 14 WT, 4 ERRαAd−/−, 6 ERRβγAd−/−, and 5 ERRαγAd−/− mice. *p < 0.05, **p < 0.01, ***p < 0.001 vs. WT BAT. WT data in panels A, C, E, and F are the accrued data of all WT littermates of ERRα floxed, ERRβγ floxed, and ERRαγ floxed mice. There were no differences between WT mice of the different cohorts. The same loading control (RAN) is presented in panels B and D. See also Figure S1, Table S3.