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 (²H) in triglycerides from very low density lipoprotein collected from blood after administration of deuterated water (D₂O) is commonly used as an indirect estimate of hepatic DNL. Here, we tested in rats (1) the feasibility to detect ²H-labeling directly in liver lipids in vivo by using noninvasive ²H 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 ²H MRS data showed ²H-labeling in the combined peak of methyl and methylene resonances after 1 week of administrati NBM_70014 on of 5% D₂O as drinking water. DNL was calculated using ¹H and ²H NMR data acquired from extracted lipids of excised liver tissue. The ²H 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 ²H 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.