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Tumor Metabolism Is Affected by Obesity in Preclinical Models of Triple-Negative Breast Cancer

SIMPLE SUMMARY: Obesity promotes both development and progression of breast cancer. As a disease, obesity is followed by hyperglycemia, hyperinsulinemia, and hyperlipidemia. The impact of obesity, accumulation of fat depots, and related markers on the metabolism of tumors still remains poorly unders...

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Detalles Bibliográficos
Autores principales: Yelek, Caner, Mignion, Lionel, Paquot, Adrien, Bouzin, Caroline, Corbet, Cyril, Muccioli, Giulio G., Cani, Patrice D., Jordan, Bénédicte F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833372/
https://www.ncbi.nlm.nih.gov/pubmed/35158830
http://dx.doi.org/10.3390/cancers14030562
Descripción
Sumario:SIMPLE SUMMARY: Obesity promotes both development and progression of breast cancer. As a disease, obesity is followed by hyperglycemia, hyperinsulinemia, and hyperlipidemia. The impact of obesity, accumulation of fat depots, and related markers on the metabolism of tumors still remains poorly understood. The aim of this study is to characterize the putative differences in the metabolism of tumors from obese and lean mice. The findings reported here could help tailor personalized treatments targeting tumor metabolism in obese cancer patients by identifying the metabolic preferences of these tumors. ABSTRACT: Obesity is characterized by an excessive fat mass accumulation associated with multiple disorders, including impaired glucose homeostasis, altered adipokine levels, and hyperlipidemia. Despite clear associations between tumor progression and obesity, the effects of these disorders on tumor metabolism remain largely unknown. Thus, we studied the metabolic differences between tumors of obese and lean mice in murine models of triple-negative breast cancer (E0771 and PY8819). For this purpose, a real-time hyperpolarized 1-(13)C-pyruvate-to-lactate conversion was studied before and after glucose administration in fasting mice. This work was completed by U-(13)C glucose tracing experiments using nuclear magnetic resonance (NMR) spectroscopy, as well as mass spectrometry (MS). Ex vivo analyses included immunostainings of major lipid, glucose, and monocarboxylic acids transporters. On the one hand, we discovered that tumors of obese mice yield higher lactate/pyruvate ratios after glucose administration. On the other hand, we found that the same tumors produce higher levels of lactate and alanine from glucose than tumors from lean mice, while no differences on the expression of key transporters associated with glycolysis (i.e., GLUT1, MCT1, MCT4) have been observed. In conclusion, our data suggests that breast tumor metabolism is regulated by the host’s physiological status, such as obesity and diabetes.