RESUMO
Abstract Maternal obesity has been described as a clinical entity associated with an increased incidence of metabolic diseases in the offspring, indicating a fetal programming phenomenon during this critical development period. Fetal exposure to an obesogenic environment affects multiple organs and tissues, including skeletal muscle, which is particularly susceptible to stressors from the external environment. Several studies have described alterations in the morphology and composition of skeletal muscle tissue secondary to obesogenic exposure in utero. In addition, modifications in signaling pathways related to the metabolism of energy substrates have been found in children born to mothers with obesity during pregnancy. This review addresses the current evidence describing the consequences of fetal exposure to an obesogenic maternal diet on skeletal muscle tissue, focusing on changes in tissue composition, alterations in signaling pathways related to glucose and fatty acid metabolism, mitochondrial biogenesis, and oxidative phosphorylation.
Resumen La obesidad materna se ha descrito como una entidad clínica asociada con el aumento en la incidencia de enfermedades metabólicas en el producto de la gestación, lo que indica la existencia de un fenómeno de programación fetal que se lleva a cabo durante este periodo crítico del desarrollo. La exposición del feto a un ambiente obesogénico afecta múltiples órganos y tejidos, incluyendo el músculo esquelético, el cual es particularmente susceptible a estresores del ambiente externo. Diversos estudios han descrito alteraciones en la morfología y composición del tejido muscular esquelético secundarias a una exposición obesogénica in utero. Además, se han encontrado modificaciones en vías de señalización relacionadas al metabolismo de sustratos energéticos en los productos de madres con obesidad durante la gestación. En la presente revisión se aborda la evidencia actual que describe las consecuencias de la exposición fetal a una dieta materna obesogénica sobre el tejido muscular esquelético, con especial enfoque en los cambios en la composición del tejido, las alteraciones en las vías de señalización relacionadas con el metabolismo de la glucosa y los ácidos grasos, así como la biogénesis mitocondrial y la fosforilación oxidativa.
RESUMO
Abstract Background Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. Objective The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). Subjects and Methods We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. Results Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. Conclusions We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.