Fructose Consumption and Hepatocellular Carcinoma Promotion

Chávez-Rodríguez, Lisette; Escobedo-Calvario, Alejandro; Salas-Silva, Soraya; Miranda-Labra, Roxana U.; Bucio, Leticia; Souza, Verónica; Gutiérrez‐Ruiz, María Concepción; Gómez–Quiroz, Luis E.

doi:10.3390/livers1040020

Cited by 4 publications

(2 citation statements)

References 62 publications

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“…187 High fructose in the diet also correlates with the progression of hepatocellular carcinoma. 188 In mice predisposed to develop intestinal tumors, modest levels of high fructose corn syrup substantially increase tumor size and grade even in the absence of obesity. 121 Overall, these results suggest that fructose could have an important effect on cancer patient's diets.…”

Section: Benefits Of Fructose Restrictionmentioning

confidence: 99%

Fructose, Another Sweet for Cancer: A Context Acting Nutrient Hypothesis

Koltai¹,

Fliegel²

2023

Gene Expr

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Rapidly proliferating cancer cells exhibit a high energy demand. However, their utilization of the glycolytic pathway is inefficient, leading to a compensatory effect wherein cancer cells consume ten to twenty times more glucose than normal cells. In cases where glucose availability is limited due to a poorly perfused hypoxic microenvironment, cancer cells resort to alternative energy sources, including fructose. Certain tumors have been found to rely heavily on fructose, and fructose utilization contributes to pro-tumoral signaling and increased cancer risk. Over the past 70 years, dietary fructose intake has steadily increased, resulting in a rise in obesity and metabolic syndrome, both of which elevate cancer risk. In this paper, we present compelling evidence that highlights the role of fructose and the glucose transporter GLUT5 in promoting specific types of tumors. We summarize the existing evidence and pathways through which fructose contributes to cancer metabolism, particularly in cases where glucose availability is restricted. Furthermore, we propose a hypothesis that elucidates the regulation of the lipogenic phenotype by dietary fructose intake and cellular energy status. It is important to note that the effects of fructose are contextdependent, with its tumor-promoting effects varying based on the energy status of the cell. We comprehensively analyze why targeting fructose uptake and fructolysis should be important for the management of some tumors and cancer prevention.

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Section: Benefits Of Fructose Restrictionmentioning

confidence: 99%

Fructose, Another Sweet for Cancer: A Context Acting Nutrient Hypothesis

Koltai¹,

Fliegel²

2023

Gene Expr

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“…Hyperpolarized 13 C MRI shows the capability of interrogating tumor metabolism, but is limited to molecules with long T 1 relaxation times on the 13 C nuclei. 9,10 Biologically important molecules, such as fructose and glucose, which are the main sources of energy in HCC, 11 have short 13 C T 1 lifetimes and thus remain challenging for applications in a clinical setting.…”

Section: Introductionmentioning

confidence: 99%

[6,6′‐²H₂] fructose as a deuterium metabolic imaging probe in liver cancer

et al. 2023

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related deaths. Imaging plays a crucial role in the early detection of HCC, although current methods are limited in their ability to characterize liver lesions. Most recently, deuterium metabolic imaging (DMI) has been demonstrated as a powerful technique for the imaging of metabolism in vivo. Here, we assess the metabolic flux of [6,6′‐2H2] fructose in cell cultures and in subcutaneous mouse models at 9.4 T. We compare these rates with the most widely used DMI probe, [6,6′‐2H2] glucose, exploring the possibility of developing 2H fructose to overcome the limitations of glucose as a novel DMI probe for detecting liver tumors. Comparison of the in vitro metabolic rates implies their similar glycolytic metabolism in the TCA cycle due to comparable production rates of 2H glutamate/glutamine (glx) for the two precursors, but overall higher glycolytic metabolism from 2H glucose because of a higher production rate of 2H lactate. In vivo kinetic studies suggest that HDO can serve as a robust reporter for the consumption of the precursors in liver tumors. As fructose is predominantly metabolized in the liver, deuterated water (HDO) produced from 2H fructose is probably less contaminated from whole‐body metabolism in comparison with glucose. Moreover, in studies of the normal liver, 2H fructose is readily converted to 2H glx, enabling the characterization of 2H fructose kinetics. This overcomes a major limitation of previous 2H glucose studies in the liver, which were unable to confidently discern metabolic flux due to overlapped signals of 2H glucose and its metabolic product, 2H glycogen. This suggests a unique role for 2H fructose metabolism in HCC and the normal liver, making it a useful approach for assessing liver‐related diseases and the progression to oncogenesis.

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