Adverse In utero and Postnatal Environments Promote Hepatic Microvesicular Steatosis in conjunction with Differential Alterations in Fatty Acid and Amino Acid Metabolism in Early Adulthood

Abstract

We questioned whether an adverse in utero environment, resulting in low birth weight (LBW), and postnatal Western diet (WD) feeding interact in hepatic steatosis pathogenesis in young males, with particular attention focused upon differential alterations in lipid and amino acid metabolism. LBW guinea pigs, generated via uterine artery ablation, and normal birth weight (NBW) controls were fed either a WD or control diet (CD) after weaning. At 150 days of age, livers were harvested for histologic, molecular and biochemical assessments, gas chromatography and mass spectrometry. In LBW/CD animals, steatosis was absent. NBW/WD animals however, displayed a macrovesicular steatosis whereas LBW/WD animals exhibited a microvesicular steatosis. Hepatic carnitine palmitoyltransferase I and uncoupling protein 2 mRNA, long‐chain acylcarnitines (C16, C18 and C18:1) and amino acids (Asp, Phe, Tyr and Trp) were lower in LBW/WD vs. NBW/WD. Independent of birth weight, WD resulted in increased hepatic triglycerides, fatty acid translocase (CD36) mRNA, expression of lipogenic genes and proteins (FAS, ACC, and HK2), and metabolite‐based lipogenic parameters (C16:1/C16:0, C18:1/C18:0 and C16:0/C18:2n‐6). Hepatic medium chain acylcarnitine (C12), long‐chain acylcarnitines (C14, C14:1, C14‐OH, C16:1, C16‐OH, C18‐OH, C18:1‐OH and C18:3) and amino acid concentrations (Arg, Cys, Thr and Leu) were increased in WD animals. In conclusion, WD and LBW/WD induce hepatic steatosis accompanied with environment specific lipid and amino acid profile alterations. These data imply a less favorable liver health prognosis for adversely in utero grown offspring fed a WD postnatally.