Fig. 3.

Hepatic PPP activity and gluconeogenesis from [U-¹³C₃]glycerol. Plasma glucose was derivatized for NMR analysis to estimate gluconeogenesis and hepatic PPP activity. A: spectra show signals of glucose carbons 2 and 5 from an 8-wk fa/fa rat and a lean littermate (+/?). Triple-labeled ([1,2,3-¹³C₃] and [4,5,6-¹³C₃]) glucose reflects gluconeogenesis directly from [U-¹³C₃]glycerol. Double-labeled (especially [5,6-¹³C₂]) glucose reflects [U-¹³C₃]glycerol metabolism via the TCA cycle. Hepatic PPP interruption in gluconeogenesis from [U-¹³C₃]glycerol produces additional [1,2-¹³C₂]glucose, causing the ratio difference between [1,2-¹³C₂]/[2,3-¹³C₂] and [5,6-¹³C₂]/[4,5-¹³C₂] in glucose. B: fractions of ¹³C-labeled glucose in both 8-wk and 16-wk fa/fa rats were lower vs. lean littermates. Levels of ¹³C-labeled glucose were similar between +/? and fa/fa rats at both ages. C: the fraction of [5,6-¹³C₂]glucose was not altered in 8-wk fa/fa rats but decreased in 16-wk fa/fa rats. The level of [5,6-¹³C₂]glucose increased in 8-wk fa/fa rats but was not changed in 16-wk fa/fa rats vs. lean littermates. D: hepatic PPP activity increased in 8-wk fa/fa rats but decreased in 16-wk fa/fa rats vs. lean littermates based on 1) the ratio difference between [1,2-¹³C₂]/[2,3-¹³C₂] and [5,6-¹³C₂]/[4,5-¹³C₂] in glucose, 2) [1,2-¹³C₂]glucose produced through the PPP, and 3) PPP flux relative to gluconeogenesis. D12, doublet from coupling of C1 with C2; D23, doublet from coupling of C2 with C3; Q, doublet of doublets, or quartet, arising from coupling of C2 with both C1 and C3 or from coupling of C5 with both C4 and C6; D45, doublet from coupling of C4 with C5; D56, doublet from coupling of C5 with C6; S, singlet; open circle, ¹²C; black circle, ¹³C. *P < 0.05; **P < 0.01; ***P < 0.001; n = 6–7 in each group.