The impact of high fat diet on global protein abundance and fractional synthetic rate in liver and mammary gland of peak lactation ICR mice

Abstract

Maternal metabolic environment creates the developmental environment for offspring. Previous studies demonstrated high fat (HF) diet increased neonate growth rate during lactation, which related to increased milk lactose content and increased fatty acyl chain length and unsaturation of milk lipids. To understand how HF diet alters maternal metabolism, we measured liver and mammary gland global protein abundance and fractional synthetic rate (FSR) of peak lactation mice after enriching body water with deuterium oxide for 24 h. In both tissues, HF altered abundance of proteins that reflected less dependence on glycolysis and a greater dependence on fatty acid degradation for energy production. Alterations in fatty acid profiles of milk due to HF diet linked to decreased abundance of enzymes that mediate de novo fatty acid synthesis and mono-unsaturation, and increased abundance of enzymes that function in the elongation and desaturation of polyunsaturated fatty acids. In the liver, HF diet increased ketogenic and gluconeogenic enzymes, indicating higher production of ketones and glucose, the former potentially linked to reduction in mammalian target of rapamycin (mTOR) abundance and the latter potentially explaining increased milk lactose content. The higher abundance of ribosomal proteins in the mammary gland of HF mice may promote greater milk production capacity and thus partly explain greater growth rate of offspring. Among proteins with significantly different FSR, HF diet decreased FSR of ~82% of the proteins in liver and ~80% in mammary. These findings enhance understanding of the impacts of diets on maternal metabolism and milk production during lactation, and expand the general understanding of how HF diet impacts metabolic pathways and proteostatic processes.