(a) Liver Sirt1, Actin and Sirt1 mRNA from CD, HFD, HFD0.3% and HFD1% fed mice (b) Liver acetylated and total FoxO1 from HFD and HFD1% fed mice. (c) Blood glucose (4 h fast), insulin, and quantitative insulin sensitivity index (QUICKI) of mice fed CD, HFD, HFD0.3% and HFD1%. (d) Liver TGs content of mice fed CD, HFD, HFD0.3%, HFD1% (n = 5/group) and fatty acid synthesis in primary hepatocytes from mice fed HFD and HFD1% (n = 6/group, representative of 2 independent experiments). (e) Serum cholesterol (4 h fast) on days 8, 15 and 32 from mice fed CD, HFD, HFD0.3% and HFD1%. (f) Cholesterol content of lipoprotein fractions from mice fed CD, HFD and HFD1%. (g) Liver and fecal cholesterol of mice fed CD, HFD, HFD0.3% and HFD1%. Cholesterol synthesis in primary hepatocytes from mice fed HFD and HFD1% (n = 6/group, representative of 3 independent experiments). (h) Effect of pharmacological Sirt1 inhibition on serum and liver cholesterol and liver TGs levels in mice fed a HFD, HFD1%, HFD1%+EX (n = 5/group). (i) Schematic representation of the proposed pathway. One-way ANOVA followed by posthoc Dunnett’s with control set to HFD: a,c,d,e,g and h. Unpaired t-test: b,d (right panel), g (right panel); n = 7 for CD, n = 8 for HFD, HFD0.3%, HFD1% in a,b,c,e,g (left panel); f pooled sample from 8 mice/group; g (middle panel) technical triplicate of pooled samples. Data are presented as mean ± s.e.m, *P < 0.05.