Fig. 2
Defective PPARα and fatty acid oxidation in liver of Vps15 mutant. a Summary plot for metabolite set enrichment analysis (the colour of the bar indicates the significance from red to yellow). All identified metabolites are listed in Supplementary Data 3. Liver tissue of six week old Vps15f/f (n = 5) and AlbCre+;Vps15f/f (n = 4) mice was collected for analyses after 6-h fasting. b Heat map showing relative levels of the fatty acids and Acyl-carnitine derivatives measured by mass spectrometry in mouse liver collected as in a. Each column corresponds to a different Vps15f/f and AlbCre+;Vps15f/f animal and the colour of the cell indicates the relative content of the metabolite (from blue to red). P < 0.05 *: vs Vps15f/f. c Hydroxybutyrate levels in plasma of six week old Vps15f/f and AlbCre+;Vps15f/f mice that were treated as in a. Data are means ± SEM (n = 5 for Vps15f/f, n = 4 for AlbCre+;Vps15f/f, P < 0.05 *: vs Vps15f/f, two-tailed, unpaired Student’s t test). d Heat map representing data from a gene expression profiling experiments performed with liver samples of mice of indicated genotypes (E-MTAB-7685 for Vps15, GSE35015 for PPARα−/−, GSE73298 for AlbCre+;PPARαf/f). All genes expression of which was significantly modified were included in the analyses. The colour of the cell indicates the relative change of expression (from blue to yellow). The genes are grouped according to their biological function in GO annotation. The gene names corresponding to GO groups are listed in Supplementary Data 4. e Relative transcript levels of rate limiting enzymes in fatty acid transport to mitochondria, ketogenesis and FAO in the livers of 6 week old random-fed or 24-h fasted prior to sacrifice Vps15f/f and AlbCre+;Vps15f/f mice. Data are means ± SEM (n = 6 for Vps15f/f, n = 4–5 for AlbCre+;Vps15f/f, P < 0.05 *: vs Vps15f/f, #: vs fed, two-tailed, unpaired Student’s t test). f Immunoblot analysis of nuclear protein liver extracts of random-fed six week old Vps15f/f and AlbCre+;Vps15f/f using indicated antibodies. Immunoblot with LaminA/C antibody served as a loading control. Densitometric analyses of protein levels normalised to LaminA/C levels presented as folds over Vps15f/f-chow condition. Data are means ± SEM (n = 4 for Vps15f/f, n = 4 for AlbCre+;Vps15f/f, P < 0.05 *: vs Vps15f/f, two-tailed, unpaired Student’s t test). g Relative levels of free fatty acids, carnitine and Acyl-carnitine in livers of 24-h fasted Vps15f/f and AlbCre+;Vps15f/f mice measured by mass spectrometry. Data are means ± SEM (n = 5, P < 0.05 *: vs Vps15f/f, two-tailed, unpaired Student’s t test)
