GSE265830 Disruption of nucleotide biosynthesis reprograms mitochondrial metabolism to inhibit adipogenesis

Contributors : Julia A Pinette ; Jacob W Myers ; Woo Y Park ; Heather G Bryant ; Genesis A Wilson ; Zer Vue ; Elizabeth R Nunn ; Matthew A Cottam ; Antentor O Hinton ; Jessica B Spinelli ; Jean-Philippe Cartailer ; Elma ZaganjorSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusA key organismal response to overnutrition involves the development of new adipocytes through the process of adipogenesis. Preadipocytes sense changes in the systemic nutrient status and metabolites can directly modulate adipogenesis. We previously identified a role of de novo nucleotide biosynthesis in adipogenesis induction, whereby inhibition of nucleotide biosynthesis suppresses the expression of the transcriptional regulators PPARg and C/EBPa. Here, we set out to identify the global transcriptomic changes associated with the inhibition of nucleotide biosynthesis. Through RNA sequencing (RNAseq), we discovered that mitochondria were the most altered transcriptional signature in response to inhibition of nucleotide biosynthesis. Blocking nucleotide biosynthesis induced rounded mitochondrial morphology, and altered mitochondrial function, and metabolism, reducing levels of tricarboxylic acid cycle intermediates, and increasing fatty acid oxidation (FAO). The loss of mitochondrial function induced by suppression of nucleotide biosynthesis was rescued by exogenous expression of PPARg. Moreover, inhibition of FAO restored PPARg expression, mitochondrial protein exp...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research