The effects of branched-chain amino acids on lactose synthesis in bovine mammary cells and mammary tissues

Abstract

Milk synthesis is a complex biological process that occurs in mammary alveoli to meet nutritional requirements of the offspring. Lactose made of glucose and galactose is the major carbohydrate in milk contributing to its energy value. Lactose is also the principal osmole drawing water into milk, and therefore, lactose production is the main determinant of milk volume having desired specific gravity. Enhancing lactose synthesis in dairy cows would be advantageous to dairy industry as the price of nearly 40% of cow milk produced in the US is determined based on milk volume. On the other hand, circumstances, such as COVID-19 would create a situation, where farmers are asked to cut back on production to mitigate the dumping of milk. Moreover, production of milk oligosaccharide having various health benefits are shown to be closely linked with lactose synthesis and lactose concentration in milk. Therefore, understanding the factors governing lactose synthesis is key to develop strategies for manipulating milk yield and its value. Essential amino acids (EAA) are hypothesized to be one of those factors as supplementation not only increases milk protein yield but also the lactose yield in dairy cows. Among EAA, branched-chain amino acids (BCAA) including leucine (Leu), isoleucine (Ile), and valine (Val) have been garnered special interest because of their abilities to elicit anabolic signals in mammary and other cells. In muscle and splanchnic tissues, Leu and Ile supply have been shown to enhance the abundance of facilitated glucose transporter 1 (GLUT1), the most prevalent glucose transporter in lactating mammary glands of dairy cows. Glucose uptake into milk secretory cells is considered as a rate limiting step of lactose synthesis. Once taken into the cells, a portion of glucose is converted to galactose, which is then transported into Golgi apparatus, where lactose synthesis takes place. The abundance of some enzymes involved in derivation of galactose and lactose synthesis have also been identified to be rate limiting for lactose synthesis. Therefore, the primary objective of this study was to determine the effects of BCAA on lactose synthesis pertaining to glucose uptake, derivation of galactose from glucose, and fractional rate of lactose synthesis (FSR) in cow mammary cells and mammary tissues. Acknowledging the knowledge gap in scientific literature, we also aimed at exploring the contribution of galactose, not derived from glucose, to lactose synthesis in the present study. A series of in vitro experiments using primary bovine mammary epithelial cells (BMEC)