Abstract
Stable isotopes are powerful tools for tracing the metabolic fate of molecules in the human body. In this chapter, we focus on the use of deuterium (2H), a stable isotope of hydrogen, in the study of human lipid metabolism within the liver in vivo in humans and in vitro using hepatocyte cellular models. The measurement of de novo lipogenesis (DNL) will be focussed on, as the synthesis of fatty acids, specifically palmitate, has been gathering momentum as being implicated in cellular dysfunction, which may be involved in the development of non-alcoholic fatty liver disease (NAFLD). Therefore, this chapter focusses specifically on the use of 2H2O (heavy water) to measure hepatic DNL.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hellerstein MK, Schwarz JM, Neese RA (1996) Regulation of hepatic de novo lipogenesis in humans. Annu Rev Nutr 16:523–557
Wilke MS, French MA, Goh YK et al (2009) Synthesis of specific fatty acids contributes to VLDL-triacylglycerol composition in humans with and without type 2 diabetes. Diabetologia 52(8):1628–1637
Solinas G, Boren J, Dulloo AG (2015) De novo lipogenesis in metabolic homeostasis: more friend than foe? Mol Metab 4(5):367–377
Schoenheimer R (1937) The investigation of intermediary metabolism with the aid of heavy hydrogen: Harvey lecture, January 21, 1937. Bull N Y Acad Med 13(5):272–295
Schoenheimer R, Rittenberg D (1935) Deuterium as an indicator in the study of intermediary metabolism. Science 82(2120):156–157
Donnelly KL, Smith CI, Schwarzenberg SJ et al (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115(5):1343–1351
Barrows BR, Parks EJ (2006) Contributions of different fatty acid sources to very low-density lipoprotein-triacylglycerol in the fasted and fed states. J Clin Endocrinol Metab 91(4):1446–1452
Diraison F, Moulin P, Beylot M (2003) Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease. Diabetes Metab 29(5):478–485
Lambert JE, Ramos-Roman MA, Browning JD et al (2014) Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 146(3):726–735
Lee JJ, Lambert JE, Hovhannisyan Y et al (2015) Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis. Am J Clin Nutr 101(1):34–43
Pramfalk C, Pavlides M, Banerjee R et al (2015) Sex-specific differences in hepatic fat oxidation and synthesis may explain the higher propensity for NAFLD in men. J Clin Endocrinol Metab 100(12):4425–4433
Pramfalk C, Pavlides M, Banerjee R et al (2016) Fasting plasma insulin concentrations are associated with changes in hepatic fatty acid synthesis and partitioning prior to changes in liver fat content in healthy adults. Diabetes 65(7):1858–1867
Timlin MT, Parks EJ (2005) Temporal pattern of de novo lipogenesis in the postprandial state in healthy men. Am J Clin Nutr 81(1):35–42
Gunn PJ, Green CJ, Pramfalk C et al (2017) In vitro cellular models of human hepatic fatty acid metabolism: differences between Huh7 and HepG2 cell lines in human and fetal bovine culturing serum. Physiol Rep 5(24):e13532
Burdge GC, Wright P, Jones AE et al (2000) A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr 84(5):781–787
Choi GT, Casu M, Gibbons WA (1993) N.m.r. lipid profiles of cells, tissues and body fluids. Neutral, non-acidic and acidic phospholipid analysis of Bond Elut chromatographic fractions. Biochem J 290(Pt 3):717–721
Semple RK, Sleigh A, Murgatroyd PR et al (2009) Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest 119(2):315–322
Diraison F, Pachiaudi C, Beylot M (1997) Measuring lipogenesis and cholesterol synthesis in humans with deuterated water: use of simple gas chromatographic/mass spectrometric techniques. J Mass Spectrom 32(1):81–86
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Pinnick, K.E., Gunn, P.J., Hodson, L. (2019). Measuring Human Lipid Metabolism Using Deuterium Labeling: In Vivo and In Vitro Protocols. In: Fendt, SM., Lunt, S. (eds) Metabolic Signaling. Methods in Molecular Biology, vol 1862. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8769-6_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8769-6_6
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8768-9
Online ISBN: 978-1-4939-8769-6
eBook Packages: Springer Protocols