RNA sequencing analysis of wildtye and Acc2 iKO mice heart in chow and HFD

Here, we show that short term HFD feeding did not change the cardiac function in normal (Con) and increased FAO mice (ACC2 iKO). RNA sequencing analysis show that ACC2 can have small but significant genetic perturbations impact on the global transcriptome under chow and HFD condition. Most of fatty acid degradation and PPAR signaling pathway related gene transcription levels were decreased by knocking out ACC2. Intriguingly, cardiac transcriptome analysis of several lipotoxicity mouse models showed an opposite regulation direction of PPAR signaling pathway and fatty acid degradation genes. Finally, fatty acid degradation gene transcription was found back to normal in iKO-HFD mouse hearts compared to Con-chow mice hearts. These results suggest that fatty acid availability may play an important role in PPAR signaling regulation regardless the fatty acid oxidation rate, at least in mice heart. Overall design: ACC2 flox/flox-MerCreMer+ (ACC2-f/f-MCM+) mice were mated with ACC2f/f to produce both study and control littermates. At 8 weeks of age, both ACC2f/f-MCM+ and ACC2f/f (CON) mice received an intraperitoneal injection of tamoxifen (20 mg/kg) for 5 days, which was sufficient to cause ACC2 deletion in ACC2f/f-MCM+ (iKO). Four weeks after the last injection of tamoxifen, male CON and iKO mice were subjected to chow or High fat diet for 16 weeks. Illumina HiSeq 2000 at a read length of 100nt single end.