Figure 6. Lactate is preferred to glucose as a fuel for the TCA cycle.

(A) Schematic for co-infusions with [U-¹³C]glucose and [3-¹³C]lactate. In short infusions, glucose-derived pyruvate and lactate are primarily m+3 and TCA cycle metabolites are primarily m+2,whereas lactate-derived metabolites are primarily m+1.

(B) Abundance of glucose and lactate pre- and post-infusion. N.S., not significant. (Student's t-test;n=3-5 samples per group)

(C) Plasma fractional enrichment of glucose and lactate during co-infusion of [U-¹³C]glucose and [3-¹³C]lactate. Data are average and S.E.M (n=8 co-infused mice).

(D) Mice with flank xenografts of HCC15 control cells were co-infused with [U¹³C]glucose and [3-¹³C]lactate. Enrichments are normalized to the enrichment of each precursor in plasma. Data areaverage and S.E.M. (n=4 mice).

(E) Mice bearing flank xenografts of HCC15 MCT1 KO cells were co-infused with [U¹³C]glucose and[3-¹³C]lactate as in (C). Enrichments are normalized to the enrichment of each precursor inplasma. Data are average and S.D. (n=2 mice).

(F) Effect of MCT1 knockout on enrichments of tumor lactate derived from circulating glucose orcirculating lactate. Data are from the infusions shown in (D) and (E) and are expressed asaverage and S.E.M.

(G) Mice bearing flank (left) and lung (right) H460 tumors were co-infused with [U-¹³C]glucose and[3-¹³C]lactate. Enrichments are normalized to enrichment of each precursor in plasma. Data areaverage and S.E.M. (n=3 mice).