Figure 2. In fasting mice, glucose labels TCA intermediates through circulating lactate in all tissues except the brain.

a–c, Normalized labelling of serum glucose, lactate, and glutamine, and of tissue TCA intermediates by infused ¹³C-lactate (a, n = 4), ¹³C-glucose (b, n = 5), and ¹³C-glutamine (c, n = 3). Data are mean ± s.d. d, Scatter plot of normalized labelling of TCA intermediates by infused ¹³C-glucose versus infused ¹³C-lactate (¹³C-glucose and ¹³C-lactate experiments performed separately). The solid line represents the expected labelling by ¹³C-glucose assuming that glucose feeds the TCA cycle solely through circulating lactate. The dashed line indicates the expected labelling by ¹³C-lactate assuming that lactate feeds the TCA cycle solely through circulating glucose. Data are from a and b, each data point is one TCA intermediate in one tissue, mean ± s.d., n = 4 for ¹³C-lactate infusion and n = 5 for ¹³C-glucose infusion. e, Direct circulating nutrient contributions to tissue TCA cycle (see Supplementary Note 3), data are mean ± s.e.m. f, Steady-state whole-body flux model of interconversion between circulating glucose and lactate and their feeding of TCA (see Supplementary Note 4), data are mean ± s.e.m.