Extended Data Fig. 3: Bmal1 depletion alters glucose metabolic flux, while G6pdx deficiency attenuates hepatocyte proliferation.
a-c, Examples of rhythmic metabolites generated from the PPP. 6-PG, 6-phosphogluconate (a); R5P, ribose-5-phosphate (b); S7P, sedoheptulose 7-phosphate (c). * P < 0.05, ** P < 0.01, *** P < 0.001. d,e, Mass isotopomer distribution of nucleotides (d) and lactate (e) derived from 13C-labeled glucose in primary hepatocytes from WT and LBKO mice. n = 4 independent biological samples. ND, not detected. f-h, Flow cytometric analysis (f) and quantification (g) of 2-NBDG intake, and measurement of lactate contents (h) in primary hepatocytes from WT and LBKO mice. n = 3 independent biological replicates. i,j, The mRNA expression of glycolytic genes Ldha and Pdk1 in hepatocytes from WT and LBKO mice with or without overexpressing G6pdx (i) and those from WT mice infected with AAV-shNC or AAV-shG6pdx (j). k,l, Representative IF images (k) and quantification (l) of staining with anti-Ki-67 and anti-G6pdx antibodies for the livers of AAV8-shNC or AAV8-shG6pdx infected mice on day 4 post-PH. Seven fluorescent fields for each of three samples were counted. Scale bar, 20 μm. m, qRT-PCR showing the mRNA levels of G6pdx in the livers of mice infected with AAV-shNC or AAV-shG6pdx for four weeks. For a-c,i,j,m, n = 3 mice per group. Data are mean ± s.e.m. P-values were calculated using two-way ANOVA with Sidak’s test (a-c,e,i), unpaired two-tailed Student’s t-test (g,h,l,m) and multiple unpaired two-tailed Student’s t-test (j).
