RT Journal Article
T1 Nutritional ketosis modulates the methylation of cancer-related genes in patients with obesity and in breast cancer cells
A1 Lorenzo, Paula M.
A1 Izquierdo, Andrea G.
A1 Rodríguez Carnero, María Gemma
A1 Costa Fraga, Nicolás
A1 Díaz Lagares, Ángel
A1 Porca, Cristina
A1 Luis, Daniel de
A1 Tejera Pérez, Cristina
A1 Paz, Laura de
A1 Cueva, Juan
A1 Bellido Guerrero, Diego
A1 Crujeiras Martínez, Ana Belén
K1 Ketogenic diet
K1 Ketone bodies
K1 Breast cancer
K1 Epigenetics
K1 Adipose tissue
K1 Tumor suppressors
K1 Oncogenes
K1 Sirtuins
K1 DNMTs
AB Scientific evidence demonstrates that a very low-calorie ketogenic diet (VLCKD) is effective and beneficial in the treatment of obesity, capable of reversing the methylome associated with obesity and has immunomodulatory capacity. This effect is in part promoted by nutritional ketosis and could be involved in counteracting obesity-related cancer. The aim of this study was to evaluate the effect of nutritional ketosis on the methylation of genes related to tumor processes in patients with obesity and in breast cancer cells. Based on methylome data (Infinium MethylationEPIC BeadChip, Illumina) from patients with obesity treated with a VLCKD for weight loss (n = 10; n = 5 women, age = 48.8 ± 9.20 years, BMI = 32.9 ± 1.4 kg/m2), genes belonging to cancer-related pathways were specifically evaluated and further validated in vitro in MDA-MB-231 (triple negative) and MCF7 (RE positive) breast tumor cells pretreated for 72 h with βOHB, the main ketone body, secretome from visceral (VATs) or subcutaneous (SATs) adipose tissue of patients with obesity. The cell tumoral phenotype was evaluated by proliferation assay and expression of cancer-related genes. VLCKD-induced nutritional ketosis promoted changes in the methylation of 18 genes (20 CpGs; 17 hypomethylated, 3 hypermethylated) belonged to cancer-related pathways with MAPK10, CCN1, CTNNA2, LAMC3 and GLI2 being the most representative genes. A similar pattern was observed in the MDA-MB-231 cells treated with β-OHB, without changes in MCF7. These epigenetic changes paralleled the tumoral phenotype modulated by the treatments. Taking together these results highlight the potential role of VLCKD as an adjuvant to anticancer treatment in groups more susceptible to the development of cancer such as patients with obesity, exerting epigenetic regulation through nutritional ketosis and weight loss.
PB Springer
YR 2025
FD 2025-03-27
LK https://hdl.handle.net/10347/42784
UL https://hdl.handle.net/10347/42784
LA eng
NO Lorenzo, P.M., Izquierdo, A.G., Rodriguez-Carnero, G. et al. Nutritional ketosis modulates the methylation of cancer-related genes in patients with obesity and in breast cancer cells. J Physiol Biochem 81, 483–498 (2025). https://doi.org/10.1007/s13105-025-01076-9
NO This work was supported by grants from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigacion; European Regional Development Fund (FEDER)–NextGenerationEU (PI20/00650, PI24/00549 and CP17/00088 research projects, CIBERobn network and IFEQ22/00147 infrastructure and Scientific-Technical Equipment), by Xunta de Galicia (IN607B-2024030) and by the PronoKal Group®, a Nestlé Health Science company. ABC is funded by a research contract “Miguel Servet” (CPII22/00008) from the ISCIII and by Servizo Galego de Saúde (SERGAS), co-financed by the European Regional Development Fund (FEDER). PML was funded by a predoctoral grant from Xunta de Galicia (IN606-2020/013). AGI was funded by a postdoctoral grant from the Fundación Instituto de Investigación Sanitaria de Santiago (FIDIS). NCF is funded by a contract as a bioinformatician (CA24/00022) from the ISCIII, co-financed by the European Regional Development Fund (FEDER). ADL is funded by Servizo Galego de Saúde (SERGAS).
DS Minerva
RD 6 jun 2026