Fig. 7. SHP-mediated repression of lipogenesis and amelioration of fatty liver in obese mice are diminished by liver-specific downregulation of DNMT3A.

C57BL/6 mice were fed normal chow diet (ND) or a high-fat /high-fructose (HF/HF) diet for 8 weeks, then infected with the combinations indicated in (a) of AAV-empty (Ctr), AAV-shDNMT3A, Ad-SHP, and Ad-empty (Ctr) and sacrificed 4 weeks later. a Experimental outline. b Levels of DNMT3A and SHP protein in the liver determined by IB. Shown are results for two mice and IB analysis was done twice. c Changes in body weight (left) and food intake (right). d Representative images of livers tissues (left) and the ratio of liver/body weight (right, n = 5). e Liver sections stained with H&E (upper panels) and Oil Red O (lower panels). Representative images are shown for one mouse in each group. Similar results were observed in two additional mice in each group. f Liver (upper) and plasma (lower) TG levels. g Glucose tolerance test (GTT) with calculated areas under the curve (AUC) plotted (right). h DNA methylation at Fasn and Srebp1 promoter regions measured by MeDIP. i Levels of mRNAs of the indicated lipogenic genes determined by RT-qPCR. j Mice were given 4% deuterated drinking water for 2 days and DNL was measured as described in methods. c, d, f–j The mean values ± SD are plotted (c, d, f–i, n = 5 mice; j, n = 3 mice). Statistical significance was determined by (d, f, g, i, j) one-way ANOVA or (h) two-way ANOVA with the Tukey post-test. *P < 0.05, **P < 0.01, ns, statistically not significant.