Figure 4.
CoQ deficiency leads to BAT dysfunction in vivo. (a) CoQ levels in BAT of BAT-specific PDSS2 knockout mice (PDSS2BKO) were decreased compared to controls (PDSS2FL) when mice were fed a defined low CoQ diet. CoQ levels in other tissues and plasma were also measured, n = 4. (b) PDSS2 and UCP1 gene expression, measured by rtPCR, in BAT was decreased in PDSS2BKO compared to PDSS2FL, n = 5–6. (c) UCP1 protein levels in BAT from knockout mice compared to control mice were decreased when assessed and quantified using western blot, n = 8. Each lane in the western blot pictured is one independent sample. (d) UCP1 gene expression was measured from BAT of wildtype mice fed a defined low CoQ diet with or without a CoQ10 supplement. CoQ10 supplementation to the diet increased UCP1 gene expression, n = 4. (e) Hematoxylin & Eosin (H&E) staining of BAT from PDSS2FL and PDSS2BKO animals, scale bar = 25 µm. BAT from PDSS2BKO animals presents a whitening phenotype compared to BAT from PDSS2FL. (f) Oxygen consumption of PDSS2FLand PDSS2BKO animals at 4 °C, measured by Comprehensive Lab Animal Monitoring System (CLAMS) (n = 3/group), showed increased cold sensitivity in PDSS2BKO animals. (g) Lipid peroxidation products malondialdehyde (MDA), measured using a TBARS assay (KGE013, R&D), was increased in BAT from knockout mice compared to controls, n = 8–9. Data represent mean ± SEM. Significance presented at * p < 0.05, ** p < 0.01, and *** p < 0.001 compared to controls or otherwise indicated.