Extended Data Figure 5: Acute knockdown of Idol in the central nervous system increases energy expenditure.
(a) Optimization of the dose of ASO required to suppress Idol expression in whole-brain homogenates measured 8-weeks post-injection. The values represent the mean expression of Idol in a whole brain homogenate 8-weeks post-injection +/− SEM; n=4 mice per time point. (b) Growth curve for male mice placed on western diet one week after intracerebroventricular injection of Idol-targeting antisense oligonucleotide (IDOL ASO) or CNS-optimized control (CTRL ASO). The mean masses are shown +/− SEM; *p<0.05, **p<0.01, ***p<0.001 by repeat measures two-way ANOVA, n=10 mice treated with CTRL and n=5 mice treated with IDOL ASO. The (c) Macroscopic view of interscapular brown adipose tissue depots after seven weeks on western diet. These images are representative of the ten mice per group in the ASO study. (d) Macroscopic view of subcutaneous (inguinal) white adipose tissue depots after seven weeks on western diet. These samples are representative of the ten mice per group in the ASO study. (e) No statistically significant differences in body composition at the onset of CLAMS experiment. The mean total body mass, lean body mass, and fat body mass are shown +/− SEM; statistical significance determined by two-way ANOVA to account for multiple testing, n=10 mice per group. The precise n-number, p-value, and details of all statistical testing are provided in the source data file file. (f) Reduced lipid accumulation in the livers of ASO treated mice evident with hematoxylin and eosin staining of 5μm sections of liver (10x objective). These images are representative of three mice per treatment group that were analyzed for histology. (g) Calculation of carbohydrate metabolism in the n=10 mice per group. The mean energy expenditure derived from carbohydrate metabolism is shown +/− SEM for each time point. (h) Calculation of lipid oxidation in the n=10 mice per group. The mean energy expenditure derived from lipid metabolism is shown +/− SEM for each time point.
