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Metabolites 2015, 5(2), 364-385; doi:10.3390/metabo5020364

Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

1
Biomarkers and Alternate Models branch, Division of Systems Biology, National Center for Toxicological Research, Jefferson, AR 72079, USA
2
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, USA
3
SiDMAP LLC, Los Angeles, CA 90064, USA
4
Los Angeles Biomedical Research Institute (LABIOMED), Torrance, CA 90502, USA
5
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA
6
Division of Pediatric Endocrinology and Diabetology, University of Ulm, Eythstr. 24, 89075 Ulm, Germany
7
Current Address: Nestle Institute of Health Sciences, 1015 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Meikle
Received: 26 February 2015 / Accepted: 9 June 2015 / Published: 16 June 2015
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Abstract

Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001). However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA) cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway) one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes. View Full-Text
Keywords: human adipocytes; fructose; glucose; [1,2-13C2]-d-glucose; targeted tracer fate association study (TTFAS); SOGC pathway human adipocytes; fructose; glucose; [1,2-13C2]-d-glucose; targeted tracer fate association study (TTFAS); SOGC pathway
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Varma, V.; Boros, L.G.; Nolen, G.T.; Chang, C.-W.; Wabitsch, M.; Beger, R.D.; Kaput, J. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway. Metabolites 2015, 5, 364-385.

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