SRA

Constant crosstalk between epigenetic regulators and metabolism homeostasis ensures that several tissues can respond and adapt to environmental cues. Decreased levels of the lysine acetyltransferase (KAT), MOF, was recently associated with cerebral development and syndromic intellectual disability. However, the consequences of having a chronic reduction of MOF levels are still unveiled. Here we characterized by FIA-MS/MS the metabolic profile of Mof heterozygous animals. We generated the profile of 8 different organs that have distinct metabolic demands. Overall, our analysis revealed that Mof heterozygous mice have impaired glucose homeostasis, fatty acids metabolism, and amino acid accumulation. When exposed ad libitum to high-fat diet those animals failed to gain fat mass, while the lean mass remains unalterable. At the molecular level, using the adipocyte model we found that Mof regulates the expression of PPARs and Slc2a4. In summary, we identified the first KAT that shows high-fat diet resistance and we propose that the chronic reduction of Mof impacts metabolic disorders.? Overall design: Wild type (control) and Mof heterozygous animals (het) were fed with either standart diet or high fat diet. To understand the intrisic role of Mof in redulating adipocyte whithe adipocyte tissue from 8 weeks-old animals under SD were sample and bulk RNAseq was performed. While to understand how diet would be affected we analyzed the transcriptome profile from WATof 27 weeks-old animals having HFD for 20 weeks. Experimentally, visceral white adipocyte tissue (WAT) was weighed and an equal amount of tissue was lysed directly in TRIZOL and samples were homogenized using an electric tissue homogenizer. Then, samples were incubated with 95% EtOH and transferred into mini-kit RNA extraction Zymo kit (R1054) and pure total RNA was extracted according to the manufacturer's instructions. RNA concentrations were quantified on a Qubit 2.0 Fluorometer (Life Technology) and quality for deep sequencing checked by Fragment analyzer. after quality control was then used to generate libraries using Illumina TruSeq RNA Sample Prep v2 (RS-122-2001). The manufacturer's recommendations were followed and the libraries were sequenced on an Illumina NovaSeq6000 sequencer. All sequence data were performed in 3 biological replicates for SD group and duplicates for HFD group. The reads were conducted at 2 x 100 bp length.