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. 2017 Apr 5;67(6):1124–1134. doi: 10.1136/gutjnl-2016-312869

Figure 3.

Figure 3

Individual miR-132 target knockdowns in diet-induced obese mice (DIO) mice fail to fully mimic the impact of transgenic miR-132 excess. (A) Experimental design: C57Bl/6J mice were fed with a high fat diet for 9 weeks, followed by a single intravenous injection of 10 mg/kg antisense (AS) GapmeRs for FoxO3, Pten, P300, Sirt1 or a negative control oligonucleotide. Mice were sacrificed 7 days post-treatment. (B) Liver weight and normalised liver/body weight in GapmeR-treated mice, showing elevation in FoxO3-AS-treated and Pten-AS-treated mice, reduction in P300-AS and no change in Sirt1-AS-treated mice (n=4). (C) H&E staining of liver sections showing variable size of fat vacuoles, with a decrease seen in Pten-AS-treated and P300-AS-treated mice. (D) Serum low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and liver triglycerides (TG) in mice treated with target AS GapmeRs (n=4). (E) Target mRNA levels, obtained from Fluidigm analysis, normalised to multiple housekeeping genes and then to negative control-treated mice (n=4), showing cross-target effects of the GapmeRs. (F) Individual and cumulative effects of each AS GapmeR on the levels of LDL/VLDL (as shown in D) compared with miR-132 dTg mice.*p<0.05, **p<0.01, ***p<0.001 (one-way analysis of variance with LSD post hoc). Bars show mean±SEM.