The Dietary Protein/Carbohydrate Ratio Differentially Modifies Lipogenesis and Protein Synthesis in the Mammary Gland, Liver and Adipose Tissue during Gestation and Lactation

Abstract

During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis.

Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation

“…However, evidence of gluconeogenic activity in the mammary tissue of guinea pigs was observed as being primarily mitochondrial due to PEPCK, a gluconeogenesis-related enzyme, where a large increase in activity of both Pck1 and Pck2 (but with a larger increase for Pck2) from pregnancy to lactation was detected (106). Increased expression of Pck1 in mammary tissue from pregnancy to lactation was also observed in rats (230). In a large transcriptomics study of the mammary tissue of dairy cows, the expression of PCK1 was not affected by lactation, whereas the expression of PCK2 was decreased (see File S3 in Ref.…”

Sex Differences: A Resultant of an Evolutionary Pressure?

“…With regard to lactation, it is well known that during gestation estrogens (Burton and Fowden, 2015;Butte, 2000) favor mammary growth and, at the same time, suppress the expression of the genes involved in lipid oxidation. The drop of estradiol levels consequent to labour promotes triglyceride synthesis (Velazquez-Villegas et al, 2013). At this stage, the metabolic role of the liver is very complementary to that of the mammary gland.…”

Transcriptional regulation of the sodium-coupled neutral amino acid transporter (SNAT2) by 17β-estradiol

“…Female Wistar rats were obtained from the animal research facility at the Instituto Nacional de Ciencias Médicas y Nutrición. The animals were housed and fed as reported (16). For experimental procedure details, see SI Materials and Methods.…”

“…Proteins from the complex purification assay or proteins extracted from rat mammary gland using a described method (16) were separated by electrophoresis, transferred onto a poly(vinylidene difluoride) …”

“…In silico analysis of the SNAT2 promoter region revealed the presence of a putative estrogen response element (ERE) between bases −1,486 and −1,471 upstream of the transcriptional start site, suggesting that the promoter region of the SNAT2 gene is regulated by 17β-estradiol and that this regulation is activated during gestation when the levels of this hormone (15) and amino acid requirements (16) increase, supporting the proliferation of the mammary tissue. The aim of this study was to elucidate the molecular mechanism by which 17β-estradiol regulates the transcription of the SNAT2 gene.…”