BioProject

The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. More...

The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining. Overall design: For RNA-sequencing, we used 4 animals for each experimental group, and we had 8 experimental groups, all of which were male mice. The groups were: [1] wildtype mice on a control-ketogenic diet (CD) fasted for 4 hours, [2] wildtype mice on a ketogenic diet (KD) fasted for 4 hours, [3] wildtype mice on a control-ketogenic diet (CD) fasted for 24 hours, [4] wildtype mice on a ketogenic diet (KD) fasted for 24 hours, [5] Fatp2-/- mice on a control-ketogenic diet (CD) fasted for 4 hours, [6] Fatp2-/- mice on a ketogenic diet (KD) fasted for 4 hours, [7] Fatp2-/- mice on a control-ketogenic diet (CD) fasted for 24 hours, and [8] Fatp2-/- mice on a ketogenic diet (KD) fasted for 24 hours, Less...