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. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: Nat Metab. 2019 Oct 28;1(11):1089–1100. doi: 10.1038/s42255-019-0127-7

Figure 4: Acute knockdown of IDOL in the central nervous system reduces adiposity by increasing energy expenditure.

Figure 4:

(a) Intracerebroventricular injection of a CNS-optimized antisense oligonucleotide (ASO) targeting Idol reduced Idol expression by 65% in the hypothalamus measured at study termination. The mean Idol expression +/− the standard error of the mean (SEM) is shown, p<0.0001 by two-tailed t-test n=8. (b) Growth curve showing the mean mass +/− SEM for male mice placed on western diet one week after ICV injection of Idol-targeting ASO or vehicle control (VEH); **p<0.01 by repeat measures ANOVA, n=10. (c) Increased VLDLR protein levels in the hypothalamus of IDOL KO mice 8 weeks after the ASO injection, the blots are representative of two independent analyses. (d) Adiposity reported as body fat percentage +/− SEM measured by MRI; n=10, ****p<0.0001 by repeat measures ANOVA (e) Hematoxylin and eosin stained subcutaneous white adipose tissue (sWAT) and interscapular brown adipose tissue (BAT) sections from mice after seven weeks of western diet feeding. (20x objective lens for sWAT and 40x objective lens for BAT, these images are representative of five independent biological replicates) (f) Energy expenditure measured by indirect calorimetry in mice after 2–3 weeks on western diet showing the mean value per hour and +/− SEM; n=10 *p<0.05 VEH vs. ASO by ANCOVA using either total body mass or lean body mass as covariates. (g) Locomotor activity as measured when a mouse crossed multiple IR beams during the calorimetry experiment; mean values +/− SEM are shown for n=10 mice. (h) No difference in the overall locomotion of mice as quantified by the cumulative number of beam breaks in a 48-hour period +/− SEM; p=0.4772 by two-tailed t-test; n=10. (i) Western blot analysis of the phosphorylation of hormone sensitive lipase (HSL) in subcutaneous white adipose tissue. This blot is representative of two independent analyses (j) Western blot analysis of tyrosine hydroxylase (TH) abundance in the brown adipose tissue. This blot is representative of two independent analyses. The precise n-number, p-value, and details of the statistical testing are provided in the source data file.