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Metabolic fate of fructose in human adipocytes: a targeted (13)C tracer fate association study.

Varma V, Boros LG, Nolen GT, Chang CW, Wabitsch M, Beger RD, Kaput J - Metabolomics (2014)

Bottom Line: A targeted stable isotope tracer fate association method was used to analyze metabolic fluxes and flux surrogates with exposure to escalating fructose concentration.This study demonstrated that fructose stimulates anabolic processes in adipocytes robustly, including glutamate and de novo fatty acid synthesis.Furthermore, fructose also augments the release of free palmitate from fully differentiated adipocytes.

View Article: PubMed Central - PubMed

Affiliation: Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079 USA.

ABSTRACT

The development of obesity is becoming an international problem and the role of fructose is unclear. Studies using liver tissue and hepatocytes have contributed to the understanding of fructose metabolism. Excess fructose consumption also affects extra hepatic tissues including adipose tissue. The effects of fructose on human adipocytes are not yet fully characterized, although in vivo studies have noted increased adiposity and weight gain in response to fructose sweetened-beverages. In order to understand and predict the metabolic responses of adipocytes to fructose, this study examined differentiating and differentiated human adipocytes in culture, exposed to a range of fructose concentrations equivalent to that reported in blood after consuming fructose. A stable isotope based dynamic profiling method using [U-(13)C6]-d-fructose tracer was used to examine the metabolism and fate of fructose. A targeted stable isotope tracer fate association method was used to analyze metabolic fluxes and flux surrogates with exposure to escalating fructose concentration. This study demonstrated that fructose stimulates anabolic processes in adipocytes robustly, including glutamate and de novo fatty acid synthesis. Furthermore, fructose also augments the release of free palmitate from fully differentiated adipocytes. These results imply that in the presence of fructose, the metabolic response of adipocytes in culture is altered in a dose dependent manner, particularly favoring increased glutamate and fatty acid synthesis and release, warranting further in vivo studies.

No MeSH data available.


Related in: MedlinePlus

Fructose induced oleate (C18:1) synthesis, acetyl-CoA formation and lactate release from adipocytes. Adipocytes were exposed to 0.1, 0.5, 1, 2.5, 5, 7.5 or 10 mM fructose in a medium containing a baseline amount of 5 mM glucose from the initiation of differentiation for 8 days (differentiating adipocytes) or 16 days (differentiated adipocytes). 10 % of fructose was supplied as [U-13C6]-fructose for a period of 48 h before harvest. Intracellular oleate content in differentiating (a) and differentiated (b) adipocytes; 13C labeled intracellular acetyl-CoA in differentiating (c) and differentiated (d) adipocytes. 13C labeled lactate fraction as percent of total unlabeled lactate in the media in differentiating (e) adipocytes and in differentiated adipocytes (f), *p < 0.05 compared to the 0.1 mM fructose labeled
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Fig5: Fructose induced oleate (C18:1) synthesis, acetyl-CoA formation and lactate release from adipocytes. Adipocytes were exposed to 0.1, 0.5, 1, 2.5, 5, 7.5 or 10 mM fructose in a medium containing a baseline amount of 5 mM glucose from the initiation of differentiation for 8 days (differentiating adipocytes) or 16 days (differentiated adipocytes). 10 % of fructose was supplied as [U-13C6]-fructose for a period of 48 h before harvest. Intracellular oleate content in differentiating (a) and differentiated (b) adipocytes; 13C labeled intracellular acetyl-CoA in differentiating (c) and differentiated (d) adipocytes. 13C labeled lactate fraction as percent of total unlabeled lactate in the media in differentiating (e) adipocytes and in differentiated adipocytes (f), *p < 0.05 compared to the 0.1 mM fructose labeled

Mentions: In addition to the increased intracellular synthesis of palmitate and its release, fructose-treated adipocytes also demonstrated an increase in the accumulation of intracellular oleate in differentiating (Fig. 5a) and differentiated (Fig. 5b) adipocytes. Oleate is formed by the elongation and desaturation of palmitate. These results imply that in addition to the activity of fatty acid synthase, fructose also increases the action of fatty acid elongase and fatty acid desaturase to bring about the conversion of palmitate to oleate thus promoting the storage of fatty acids as both oleate and palmitate. Oleate synthesis was distinctly higher in the differentiated adipocytes (Fig. 5b) compared to the differentiating adipocytes (Fig. 5a). No change was observed in the release of oleate into the medium in response to fructose treatment (data not shown).Fig. 5


Metabolic fate of fructose in human adipocytes: a targeted (13)C tracer fate association study.

Varma V, Boros LG, Nolen GT, Chang CW, Wabitsch M, Beger RD, Kaput J - Metabolomics (2014)

Fructose induced oleate (C18:1) synthesis, acetyl-CoA formation and lactate release from adipocytes. Adipocytes were exposed to 0.1, 0.5, 1, 2.5, 5, 7.5 or 10 mM fructose in a medium containing a baseline amount of 5 mM glucose from the initiation of differentiation for 8 days (differentiating adipocytes) or 16 days (differentiated adipocytes). 10 % of fructose was supplied as [U-13C6]-fructose for a period of 48 h before harvest. Intracellular oleate content in differentiating (a) and differentiated (b) adipocytes; 13C labeled intracellular acetyl-CoA in differentiating (c) and differentiated (d) adipocytes. 13C labeled lactate fraction as percent of total unlabeled lactate in the media in differentiating (e) adipocytes and in differentiated adipocytes (f), *p < 0.05 compared to the 0.1 mM fructose labeled
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig5: Fructose induced oleate (C18:1) synthesis, acetyl-CoA formation and lactate release from adipocytes. Adipocytes were exposed to 0.1, 0.5, 1, 2.5, 5, 7.5 or 10 mM fructose in a medium containing a baseline amount of 5 mM glucose from the initiation of differentiation for 8 days (differentiating adipocytes) or 16 days (differentiated adipocytes). 10 % of fructose was supplied as [U-13C6]-fructose for a period of 48 h before harvest. Intracellular oleate content in differentiating (a) and differentiated (b) adipocytes; 13C labeled intracellular acetyl-CoA in differentiating (c) and differentiated (d) adipocytes. 13C labeled lactate fraction as percent of total unlabeled lactate in the media in differentiating (e) adipocytes and in differentiated adipocytes (f), *p < 0.05 compared to the 0.1 mM fructose labeled
Mentions: In addition to the increased intracellular synthesis of palmitate and its release, fructose-treated adipocytes also demonstrated an increase in the accumulation of intracellular oleate in differentiating (Fig. 5a) and differentiated (Fig. 5b) adipocytes. Oleate is formed by the elongation and desaturation of palmitate. These results imply that in addition to the activity of fatty acid synthase, fructose also increases the action of fatty acid elongase and fatty acid desaturase to bring about the conversion of palmitate to oleate thus promoting the storage of fatty acids as both oleate and palmitate. Oleate synthesis was distinctly higher in the differentiated adipocytes (Fig. 5b) compared to the differentiating adipocytes (Fig. 5a). No change was observed in the release of oleate into the medium in response to fructose treatment (data not shown).Fig. 5

Bottom Line: A targeted stable isotope tracer fate association method was used to analyze metabolic fluxes and flux surrogates with exposure to escalating fructose concentration.This study demonstrated that fructose stimulates anabolic processes in adipocytes robustly, including glutamate and de novo fatty acid synthesis.Furthermore, fructose also augments the release of free palmitate from fully differentiated adipocytes.

View Article: PubMed Central - PubMed

Affiliation: Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079 USA.

ABSTRACT

The development of obesity is becoming an international problem and the role of fructose is unclear. Studies using liver tissue and hepatocytes have contributed to the understanding of fructose metabolism. Excess fructose consumption also affects extra hepatic tissues including adipose tissue. The effects of fructose on human adipocytes are not yet fully characterized, although in vivo studies have noted increased adiposity and weight gain in response to fructose sweetened-beverages. In order to understand and predict the metabolic responses of adipocytes to fructose, this study examined differentiating and differentiated human adipocytes in culture, exposed to a range of fructose concentrations equivalent to that reported in blood after consuming fructose. A stable isotope based dynamic profiling method using [U-(13)C6]-d-fructose tracer was used to examine the metabolism and fate of fructose. A targeted stable isotope tracer fate association method was used to analyze metabolic fluxes and flux surrogates with exposure to escalating fructose concentration. This study demonstrated that fructose stimulates anabolic processes in adipocytes robustly, including glutamate and de novo fatty acid synthesis. Furthermore, fructose also augments the release of free palmitate from fully differentiated adipocytes. These results imply that in the presence of fructose, the metabolic response of adipocytes in culture is altered in a dose dependent manner, particularly favoring increased glutamate and fatty acid synthesis and release, warranting further in vivo studies.

No MeSH data available.


Related in: MedlinePlus