Western diet consumption through early life induces microvesicular hepatic steatosis in association with an altered metabolome in low birth weight Guinea pigs.

Uteroplacental insufficiency-induced low birth weight (LBW) and postnatal high saturated fat/high sucrose-fructose diet (Western Diet, WD) consumption have been independently associated with the development of hepatic steatosis, while their additive effect on fatty acid, acylcarnitine and amino acid profiles in early adulthood have not been widely reported. We employed LBW, generated via uterine artery ablation, and normal birth weight (NBW) male guinea pigs fed either a WD or control diet (CD) from weaning to postnatal day 150 (early adulthood). Hepatic steatosis was absent in CD-fed offspring, while NBW/WD offspring displayed macrovesicular steatosis and LBW/WD offspring exhibited microvesicular steatosis, both occurring in a lean phenotype. Life-long consumption of the WD, irrespective of birth weight, was associated with an increase in hepatic medium- and long-chain saturated fatty acids, monounsaturated fatty acids, acylcarnitines, reduced oxidative phosphorylation complex III activity and polyunsaturated fatty acids, and molecular evidence of disrupted hepatic insulin signaling. In NBW/WD, hepatic C15:1 and C16:1n-6 fatty acids in phospholipids, C16, C18 and C18:1 acylcarnitines, concentrations of aspartate, phenylalanine, tyrosine and tryptophan and expression of carnitine palmitoyltransferase 1 alpha (CPT1α) and uncoupling protein 2 (UCP2) genes were elevated compared to LBW/WD livers. Our results suggest that LBW and life-long WD combined are influential in promoting hepatic microvesicular steatosis in conjunction with a specific mitochondrial gene expression and metabolomic profile in early adulthood.