Figure 4. SIRT6 Deficiency Inhibits PPARα-Regulated Metabolic Pathways.

(A) Scheme depicting SIRT6 regulation of metabolic pathways via PPARα.

(B) Western blot analysis of pyruvate oxidation signaling following WY treatment (50 mg/kg) (left) in WT mice, and in WT versus HZ WY-treated mice (middle), and ImageJ quantification (right). Tubulin was used as loading control and CMC 0.1% was used as control for the WY.

(C) β-oxidation pathway measurements including quantitative real-time PCR analysis of mRNA levels of fatty acid transporter Cd36 (left), metabolite acetylcarnitine C2 (middle), and CO₂ levels from ¹⁴C-labeled palmitate in mitochondria (right) from WY-treated control and SIRT6 HZ livers.

(D) Quantitative real-time PCR analysis of mRNA levels of glycerol transporter Aqp3.

(E) Gluconeogenic precursor metabolites lactate (left) and amino acid alanine (right).

(F) Quantitative real-time PCR analysis of mRNA levels of glycogenolysis and glycogen synthesis enzymes Pygl and Gys2, respectively. In (B)–(F), all from livers of WT and HZ mice following control (CMC) or WY treatment.

(G and H) Metabolites (G) and quantitative real-time PCR analysis of mRNA levels in livers of fasted WT and SIRT6 TG mice (H).

In (B)–(H) proteins and genes are represented as means + SE and metabolites are represented as means + max/min; *p < 0.05, **p < 0.01. In (B), (G), and (H) a two-tail Student’s t test was used; n = 6–7 per genotype. In (C)–(F), two-way ANOVA followed by a Bonferroni multiple comparisons test were used; n = 6–7 per genotype.