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Knockdown of the nucleoside diphosphate linked moiety X-type motif Nudt19 increases fatty acid oxidation and ATP production in murine liver cells

ABSTRACT: Changes in intracellular CoA levels are known to contribute to the development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D). The underlying genetic basis for the development and progression of these complex disorders, however, is still poorly understood. Due to their diverse susceptibility towards metabolic diseases, mouse inbred strains have been proven to serve as powerful tools in the identification of novel genetic factors that are fundamental in the pathophysiology of diabetes and NAFLD. Transcriptome analysis revealed the nucleoside diphosphate linked moiety X type motif Nudt19 as novel candidate gene responsible for NAFLD and T2D development. Knockdown (KD) of Nudt19 increased both mitochondrial and glycolytic ATP production rates in Hepa 1-6 cells. The enforced utilization of glutamine or fatty acids as energy substrate reduced uncoupled respiration in NT cells. This reduction was prevented upon knockdown of Nudt19. Furthermore, incubation with palmitate or oleate increased mitochondrial ATP production and uncoupled respiration in Nudt19 KD cells, but not in NT cells. The enhanced fatty acid oxidation in Nudt19 KD cells was accompanied by an increased abundance of Pdk4. This study describes for the first time Nudt19 as regulator of hepatic lipid metabolism and potential mediator of NAFLD and T2D development.

ORGANISM(S): Mus musculus

PROVIDER: GSE186106 | GEO | 2022/04/11

REPOSITORIES: GEO

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