Extended Data Figure 10.

Effect of mGPD and cGPD antisense oligonucleotide (ASO) treatment on liver toxicity and tissue-specific knockdown of mGPD expression by mGPD ASO. (a) mGPD ASO treatment had no effect on body weight after treatment at 37.5 mg/kg ASO twice a week for 4 weeks. (b) All ASOs screened in this study, mGPD ASO #1, mGPD ASO #2, cGPD ASO #1 and cGPD ASO #2 elicited no significant liver toxicity as determined by plasma AST/ALT levels after 4 weeks. (c) Treatment with mGPD ASO #2 for 4 weeks during the mGPD ASO with acute metformin study also had no effect on plasma AST/ALT. (d) mGPD ASO treatment led to cleavage of mGPD mRNA transcript exclusively in the liver, only slightly decreasing transcript levels in white adipose tissue and having no effect on mGPD mRNA in other tissues. (e–k) mGPD ASO treatment specifically reduced protein expression of mGPD in the liver, with no significant effect on mGPD protein levels in the pancreas, kidney, muscle, white adipose or brown adipose. Data are mean ± SEM, (n=6 biological replicates). * P<0.05, **P<0.01, ***P<0.001 by unpaired t-test.