Fig. 7
PPARα activates mitochondrial biogenesis in liver. a Heat map representing data from a microarray experiment performed with liver samples of PPARαf/f and AlbCre+;PPARαf/f mice treated with fenofibrate (GSE73298) or fasted for 24 h (GSE73299). The colour of the cell indicates the relative change of expression (from blue to yellow). The genes are grouped according to their GO annotations (biological function). The gene names corresponding to GO groups are listed in Supplementary Data 5. b Relative mRNA expression levels of mitochondrial transcription factors, respiratory chain subunits and genes of FAO in liver tissue of PPARαf/f and AlbCre+;PPARαf/f mice treated with fenofibrate37. Data are means ± SEM (n = 6, P < 0.05 *: vs PPARαf/f, #: vs chow, two-tailed, unpaired Student’s t test). Mitochondrial versus nuclear DNA was determined by quantitative PCR analysed in total DNA purified from liver tissue of fed or 24-h fasted Vps15f/f and AlbCre+;Vps15f/f mice (c) or PPARαf/f and AlbCre+;PPARαf/f mice37 (d). Mitochondrial genome coded ND2 gene served as read-out of mtDNA and Tert1 as read-out of nuclear genome. Data are means ± SEM (n = 4–6 for Vps15f/f, n = 4–5 for AlbCre+;Vps15f/f, n = 5–6 for PPARαf/f and AlbCre+;PPARαf/f; P < 0.05 *: vs wild-type mice, #: vs fed, two-tailed, unpaired Student’s t test). Relative mRNA (e) and protein (f) expression levels of indicated genes in primary hepatocytes incubated for 72 h in control or fasting media. Data are means ± SEM (n = 3, P < 0.05 *: vs control media, two-tailed, unpaired Student’s t test). g Schematic representation of putative PPRE localization in the promoter regions of mouse Tfam and Tfb2m genes (top panel). White rectangles represent exons, black rectangles—putative PPREs. Relative enrichment of endogenous PPARα on putative PPREs in promoter region of Tfam and Tfb2m genes analysed by qPCR on chromatin prepared from primary hepatocytes (bottom panel). Binding of PPARα to PPRE in its own promoter served as a positive control. Data are means ± SEM, average of n = 7–8 immunoprecipitations. P < 0.05 *: vs IgG, two-tailed, unpaired Student’s t test. h Proposed model depicting the class 3 PI3K which controls PPARα activation for lipid degradation and mitochondrial biogenesis during fasting
