Abstract 1785: The role of BRCA1 on metabolic pathways in an in vivo system

Abstract

Abstract The role of BRCA1 in cellular metabolism is not well characterized and what we do understand has been mostly demonstrated in vitro. Our studies aim to fully characterize the role of BRCA1 in metabolic pathways in a whole-body system. In vivo studies using C57BL/6 wild-type and transgenic humanized BRCA1 mice demonstrate the effect of human BRCA1 on the whole-body metabolic phenotype and start to elucidate the mechanism by which this occurs. We used Promethion metabolic chambers and glucose tolerance tests to measure a number of metabolic outputs of male and female mice that had either normal mouse Brca1 gene expression (wild-type/WT mice) or a knock-out mouse Brca1/knock-in human BRCA1 (humanized/HU mice). Humanized BRCA1 mice are more lean, hyperactive and demonstrate a sexual dimorphism in glucose tolerance when compared to wild-type mice on the same genetic background. To begin to elucidate the mechanisms behind the observed metabolic phenotype, we used a metabolic tissue, female mouse skeletal muscle, to perform mass spectrometry, SuperArray, and Western blot analysis. Proteomic samples were sent to the IDeA National Resource for Quantitative Proteomics at the University of Arkansas Medical Sciences for processing and analysis. Proteomic and genomic analysis showed changes in a number of metabolic pathways that may be implicated in the observed whole body metabolic phenotype. We can conclude that changing the expression levels of BRCA1 in an in vivo model altered the overall metabolic profile of C57BL/6 mice. This is the first in vivo evidence demonstrating the effects of BRCA1 expression in whole body metabolism. Citation Format: Stacey L. Hembruff, Alexander Dekonenko, John Thyfault, Mihaela Sardiu, Michael Washburn, Roy A. Jensen, Lisa M. Harlan-Williams. The role of BRCA1 on metabolic pathways in an in vivo system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1785.