Using [2H]water to quantify the contribution of de novo palmitate synthesis in plasma: Enabling back-to-back studies

12Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

An increased contribution of de novo lipogenesis (DNL) may play a role in cases of dyslipidemia and adipose accretion; this suggests that inhibition of fatty acid synthesis may affect clinical phenotypes. Since it is not clear whether modulation of one step in the lipogenic pathway is more important than another, the use of tracer methods can provide a deeper level of insight regarding the control of metabolic activity. Although [2H]water is generally considered a reliable tracer for quantifying DNL in vivo (it yields a homogenous and quantifiable precursor labeling), the relatively long half-life of body water is thought to limit the ability of performing repeat studies in the same subjects; this can create a bottleneck in the development and evaluation of novel therapeutics for inhibiting DNL. Herein, we demonstrate the ability to perform back-to-back studies of DNL using [2H]water. However, this work uncovered special circumstances that affect the data interpretation, i.e., it is possible to obtain seemingly negative values for DNL. Using a rodent model, we have identified a physiological mechanism that explains the data. We show that one can use [2H]water to test inhibitors of DNL by performing back-to-back studies in higher species [i.e., treat nonhuman primates with platensimycin, an inhibitor of fatty acid synthase]; studies also demonstrate the unsuitability of [13C]acetate.

Cite

CITATION STYLE

APA

Previs, S. F., Herath, K., Nawrocki, A. R., Rodriguez, C. G., Slipetz, D., Singh, S. B., … Kelley, D. E. (2018). Using [2H]water to quantify the contribution of de novo palmitate synthesis in plasma: Enabling back-to-back studies. American Journal of Physiology - Endocrinology and Metabolism, 315(1), E63–E71. https://doi.org/10.1152/ajpendo.00010.2017

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free