Fig. 5

Metabolic changes after 4-IPP or metformin treatments. The figure shows the bargraphs relative of the metabolites analysed by mass spectrometry after C2 treatments with 4-IPP at 100 μM for 24 h and metformin at 5 mM for 120 h. Values are expressed as ng/mg proteins and are normalized to the value of total proteins present in each sample. Each value represents the mean of five independent replicates. Metabolites values are also plotted; blue bars mark the amount with respect to the highest values. Metabolic organic acids intermediates of the TCA cycle (citrate, succinate and fumarate) were reduced both in 4-IPP and metformin treated cells. In the case of metformin treated cells, there was a significant increase in lactate production, suggestive of an inefficient pyruvate-dehidrogenase activity due to impaired TCA and OXPHOS. Citrate released by mitochondria is converted into Acetyl-CoA, NADPH and ATP for lipid (cholesterol and fatty acids) synthesis. Cholesterol and precursor sterols (markers of cholesterol synthesis) were reduced in both 4-IPP and metformin treated cells. Very long chain fatty acids (>C16) were reduced by both treatments