Fig. 7: The effect of SIRT1 modulators on hepatic steatosis, mitochondrial characteristics, SIRT1, and its downstream targets. | Nature Communications

Fig. 7: The effect of SIRT1 modulators on hepatic steatosis, mitochondrial characteristics, SIRT1, and its downstream targets.

From: The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction

Fig. 7: The effect of SIRT1 modulators on hepatic steatosis, mitochondrial characteristics, SIRT1, and its downstream targets.The alternative text for this image may have been generated using AI.

a Relative mtDNA copy number (mtDNA/beta-globin) (n = 6 per group). b ATP levels (n = 6 per group). c Relative expression of β-oxidation genes (n = 6 per group). d Relative expression of lipid genesis genes (n = 6 per group). e SIRT1 activity (n = 6 per group). g Quantification of SIRT1 and PGC-1α protein levels in western blots (n = 6 per group). f Representative SIRT1 and PGC-1α western blots. One-way ANOVA followed by Tukey’s post hoc test. Unless stated differently in the figure legend, all n represents biologically independent samples. Data are shown as the mean ± SEM. Scale bars are as indicated. h Proposed model: In protein malnutrition, decreased tryptophan availability will decrease the tryptophan–kynurenine pathway activity, which is associated with NAD+ and NAM deficiency. This would disturb NAD+ salvage pathway, including SIRT1, influence its downstream target PGC-1α and autophagy, which affect mitochondrial health. These changes lead to ATP depletion and lipid accumulation in the liver. We hypothesize that supplement with TRP-NAD+ modulator would influence NAD+ salvage pathway. This would thereby activate SIRT1, influence PGC-1α and autophagy pathway, which will have a positive effect on mitochondrial biogenesis and clearance of damaged mitochondrial, then improve ATP generation and reduce lipid accumulation in the liver.

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