Deuterium MRS for In Vivo Measurement of Lipogenesis in the Liver

ABSTRACT Hepatic de novo lipogenesis (DNL) plays a key role in the pathogenesis of several metabolic diseases that affect the liver. In humans, the detection of deuterium ( 2 H) in triglycerides from very low density lipoprotein collected from blood after administration of deuterated water (D 2 O) is commonly used as an indirect estimate of hepatic DNL. Here, we tested in rats (1) the feasibility to detect 2 H‐labeling directly in liver lipids in vivo by using noninvasive 2 H MRS and (2) to what extent these results correlated with the gold standard measurement of DNL in excised liver tissue. To increase hepatic DNL, half of the animals ( n = 4) underwent a 7‐week dietary intervention in which fructose was provided in drinking water. Deuterium MRS data were acquired from a single voxel placed in the liver. In vivo 2 H MRS data showed 2 H‐labeling in the combined peak of methyl and methylene resonances after 1 week of administrati NBM_70014 on of 5% D 2 O as drinking water. DNL was calculated using 1 H and 2 H NMR data acquired from extracted lipids of excised liver tissue. The 2 H lipid level measured in vivo correlated with the ex vivo estimates of hepatic DNL ( r = 0.81, p = 0.016). These results demonstrate the feasibility of direct detection of deuterium labeling in liver lipids using localized 2 H MRS in vivo and indicate the potential of this approach to measure hepatic DNL. These initial observations provide a basis for the method to be translated and to develop noninvasive, quantitative measurements of hepatic DNL in humans.