Effects of High-Fat Feeding on Expression of Genes Regulating Fatty-1 Acid Metabolism in Hearts of Pregnant C57BL/6 Mice

Abstract

Cardiovascular complications in pregnancy increase risk for subsequent heart disease, suggesting adverse events during pregnancy may permanently alter maternal heart health. The heart undergoes physiologic hypertrophy with pregnancy, which is distinct from pathological remodeling associated with obesity. We previously demonstrated that C57BL/6 mice fed a high-fat diet, a model of diet-induced obesity, had attenuated cardiac hypertrophy with pregnancy compared to low-fat controls, associated concentric remodeling. Dual effects of pregnancy and obesity on cardiac metabolism during hypertrophy have not been studied. We investigated whether expression of genes regulating fatty acid metabolism in the heart were altered in pregnant mice fed a high-fat diet. The Nanostring Metabolic Pathways Panel and nCounter analysis system was used to quantify individual mRNA transcripts of genes regulating fatty acid metabolism from the left ventricles of pregnant and non-pregnant female C57BL/6 mice fed a high-fat or control low-fat diet. Pregnancy increased expression of genes regulating fatty acid transport (Cd36, Slc27a1, Cpt1b) and β-oxidation (Acaa2, Acadl, Acox1, Ehhadh, Mlycd), but the effect was observed in low-fat mice only. Increases in gene expression with high-fat feeding were pronounced in non-pregnant mice, but effects not additive with pregnancy. Further, three genes with functions related to energy metabolism (Glul, Mat2a, Ogdhl,) were increased in low fat–fed pregnant mice only. Obesity during pregnancy may “max out” cardiac fatty acid utilization through upregulation of transporters and oxidation of long-chain fatty acids, and also downregulate metabolic pathways essential to cardiac adaptation. These 48 results suggest pre-existing obesity could disrupt cardiac physiologic remodeling during pregnancy.