Maternal High-Fat Diet Increases Fetal Muscle Fat Metabolism and Fatty Acid Transporter Expression in an Ovine Model

Abstract

ObjectivesExcessive maternal dietary fat consumption during pregnancy may be linked to adverse effects on offspring health, including greater risk of developing metabolic syndrome later in life. Metabolic syndrome is generally considered to be a preventable condition, but the extent to which it is “programmed” during fetal development remains unclear. The aim of this study was to determine the effect of a maternal high-fat diet (MHFD) during pregnancy on fetal muscle oxidative metabolism and related protein and mRNA expressions in an ovine model. MethodsWhite-faced ewes were fed either a control diet (Show-rite NewCo Lamb Feed-17% protein, 5% Fat) or a high-fat diet (Show-rite NewCo Lamb Feed + 6% Rumen-protected Fat) from 2–3 weeks before pregnancy until mid-gestation (75 days), when a C-section was performed to collect the placenta and fetal tissues for analysis. ResultsMHFD tended to increase fetal body and organ weights, but only significantly increased fetal body length and liver mass (P < 0.05). MHFD increased mRNA expression of placental (cotyledon) fatty acid transport protein-1 (FATP-1) and peroxisome proliferator activated receptor gamma, suggesting an upregulation of placental fatty acid metabolism and transport. Fetal muscle fatty acid oxidation capacity was greater in animals from MHFD pregnancies, with no effect on pyruvate oxidation. This was associated with greater fetal muscle mRNA and protein expression of FATP4, while mRNA expression glucose transporters (GLUT1 and GLUT3) decreased. Muscle expression of insulin signaling enzymes reflected a mild decreases in insulin sensitivity, but these did not reach statistical significance. ConclusionsThese studies indicate that MHFD induces an increase in placental and fetal muscle fatty acid transport and oxidation capacity, and favors lower blood glucose uptake compared to controls. Whether these shifts in fetal metabolism predispose offspring from MHFD pregnancies to elevated blood sugar and Type 2 diabetes later in life merits further investigation. Funding SourcesColorado Agricultural Experiment Station.