Fig. 7. HADHA suppressed hepatic glucagon response dependent on BDH1 in HFD-fed mice.

Eight-week-old mice injected with AAV8-NC, AAV8-HADHA or AAV8-BDH1 shRNA were fed with NCD or HFD for 12 weeks. a Serum glucagon contents in mice (n = 4). b, c BHB contents in serum and liver (b: n = 5; c: n = 4). d Pyruvate tolerance test (2 g/kg body weight) after 11 weeks of feeding. AUC is indicated on the right (n = 6). e Fasting blood glucose after 12 weeks of feeding (n = 6). f Oral glucose tolerance test (2.5 g/kg) after 12 weeks of feeding. AUC is indicated on the right (n = 5). g Representative images of HE and Oil Red O-stained liver sections (n = 3). h Protein expressions of FOXO1, HDAC4, HDAC5 and HDAC7 in nucleus and cytoplasm of liver (n = 3). i Hepatic FOXO1 acetylation levels. It was repeated 3 times independently with similar results. j Western blotting analysis of HADHA and FOXO1 phosphorylation in the liver (n = 3). k Relative mRNA levels of Pck1, G6pc and Pgc1a in the liver (n = 5). AAV adeno-associated virus, AUC area under the curve, BHB β-hydroxybutyrate, HFD high-fat diet, NCD normal chow diet. Values represent mean ± SEM. Statistical differences were determined by one-way ANOVA. Source data are provided as a Source Data file.