Expression of SIRT1 in human fetal and adult liver and isolated hepatocytes.

<p>(A) Immunohistochemistry of SIRT1 in human fetal and adult liver, (B) Immunofluorescence staining of SIRT1 in fetal and adult hepatocytes after 2 days of culture. (C) Quantification of hepatic SIRT1 mRNA expression measured by qRT- PCR in human fetal and adult hepatocytes in vitro and in vivo (n≥3/group).</p

Increased activation of Glucogenesis pathway in human fetal hepatocytes after exposure to Sirtinol.

<p>(A) Expression of hepatic PEPCK and G6PC mRNA measured by qRT- PCR in human fetal hepatocytes exposed to +50uM Sirtinol compared to controls. (B) Immunofluorescence of S-473 AKT in human fetal hepatocytes with or without 50uM Sirtinol (10x). (C) Fluorescence intensity quantification for S-473 AKT signal (arbitrary units) using ImageJ (n≥7/group; *, P < .05). (D) Western blot analysis for S-473 AKT/AKT, S-256 FOXO1/FOXO1 in human fetal hepatocytes exposed to 50uM Sirtinol compared to controls. GAPDH was used as a loading control. (E) Immunofluorescence staining of S-256 FOXO1 in human fetal hepatocytes with or without 50uM Sirtinol (20x).</p

Expression of SIRT1 in human fetal and adult liver and isolated hepatocytes.

<p>(A) Immunohistochemistry of SIRT1 in human fetal and adult liver, (B) Immunofluorescence staining of SIRT1 in fetal and adult hepatocytes after 2 days of culture. (C) Quantification of hepatic SIRT1 mRNA expression measured by qRT- PCR in human fetal and adult hepatocytes in vitro and in vivo (n≥3/group).</p

Lipids and glucose levels in human fetal hepatocytes after Sirt1 inhibition.

<p>(A) Fluorescent staining of lipids (red droplets, white arrow) inside human fetal hepatocytes (HFH) with or without 50uM Sirtinol for 3 days (20x). (B) Triglycerides quantification of human fetal hepatocytes with or without +50uM Sirtinol for 3 days analyzed by a colorimetric assay. (C) Glucose concentration between normal HFH and HFH +50uM Sirtinol for 3 days. (n≥7/group; *, P < .05).</p

Donor Demographics.

<p>Donor Demographics.</p

Representation of SIRT1 regulation of lipid and glucose balances in human fetal hepatocytes.

<p>In normal conditions, SIRT1 inhibits De Novo Lipogenesis and Gluconeogenesis through the AKT/FOXO1 pathway inside human fetal hepatocytes, keeping a normal balance inside the cells. Upon SIRT1 inhibition, both the lipid and glucose balance will be disrupted, leading to an increase of lipid and carbohydrates levels in human fetal hepatocytes.</p