Figure 1.

MiR-29a prevents PI3K-Akt-mTORup-regulation and and its delivery to the arcuate nucleus attenuates obesity in adult mice. (A) Quantification of pS6 signal in HeLa cells transfected with indicated human microRNA inhibitors or treated with 300 nM insulin or 500 nM rapamycin (n = 3). (B) Scheme illustrating phylogenetic conservation of the miR-29 family. Both clusters on each of the chromosomes (chr.) in mice and humans are aligned to each other, transcription direction is shown by a red arrow on the left, genetic positions are indicated. (C) TaqMan qPCR analysis of mature forms of guide (bottom) and passenger (top) strands of the miR-29 family in the wild type mouse hypothalamus compared to U6 RNA (n = 4). (D–G) MicroRNA mimic injection to DicerCKO mice with the scheme of the experiment (D), body weight (E), fat pad weights (F) and food intake (G) analyses. Liposomal formulation of miR-29a-3p mimics was injected bilaterally to the arcuate hypothalamic nucleus of adult DicerCKO female mice on the 4th week after tamoxifen treatment. n = 9, 4 and 5 for Control-Scrambled (C–S), DicerCKO-Scrambled (D–S) and DicerCKO-miR-29a-3p mimic (D-29) groups, respectively. Error bars represent SEM. ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; ∗∗∗∗, p < 0.0001 as assessed by 1-way (A,F) or 2-way (E,G) ANOVA followed by post-hoc Holm–Sidak tests with significances indicated vs. the control group or vs. the groups outlined with a respective color.