Hyperpolarized [13C]bicarbonate is a noninvasive metabolic biomarker of fatty liver in humans

Motivation: Changes in pyruvate flux toward the mitochondria via pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) remain controversial. Goal(s): This study is to assess hepatic mitochondrial metabolism via [13C]bicarbonate from [1-13C1]pyruvate and glycerol glyceroneogenesis in relation to hepatic fat content. Approach: Fifteen subjects received hyperpolarized [1-13C1]pyruvate and [U-13C3]glycerol. Time-resolved 13C MRS and plasma 13C NMR were acquired. Results: Participants with high liver fat produced reduced hyperpolarized [13C]bicarbonate. The fraction of plasma [5,6-13C2]glucose (PC) decreased in fatty liver whereas the fraction of [4,5-13C2]glucose+[6-13C1]glucose (PC+PDH) was unaltered, suggesting a shifted pyruvate metabolism with a decreased ratio of flux through PC relative to PDH. Impact: Noninvasive assessment of PC and PDH pathways is important for identifying the role of mitochondrial metabolism in hepatic steatosis. The demonstrated method provides metabolic insights into fatty liver and is applicable for investigating other liver diseases with impaired mitochondrial function.