Profiling solute-carrier transporters in key metabolic tissues during the postpartum evolution of mammary epithelial cells from nonsecretory to secretory

Abstract

Modifications in the abundance of solute-carrier (SLC) transcripts in tandem with adjustments in genes-associated with energy homeostasis during the postpartum transition of the mammary epithelial cells (MEC) from nonsecretory to secretory is pivotal for supporting milk synthesis. The goal of this study was to identify differentially expressed SLC genes across key metabolic tissues between late pregnancy and onset of lactation. Total RNA was isolated from the mammary, liver, and adipose tissues collected from rat dams on day 20 of pregnancy (P20) and day 1 of lactation (L1) and gene expression was measured with Rat 230 2.0 Affymetrix GeneChips. LIMMA was utilized to identify the differential gene expression patterns between P20 and L1 tissues. Transcripts engaged in conveying anions, cations, carboxylates, sugars, amino acids, metals, nucleosides, vitamins, and fatty acids were significantly increased ( P < 0.05) in MEC during the P20 to L1 shift. Downregulated ( P < 0.05) genes in the mammary during the physiological transition included GLUT8 and SLC45a3. In the liver, SLC genes encoding for anion, carbonyl, and nucleotide sugar transporters were upregulated ( P < 0.05) at L1. while genes facilitating transportation of anions and hexose were increased ( P < 0.05), from P20 to L1 in the adipose tissue. GLUT1 and GLUT4 in the liver, along with GLUT4 and SGLT2 in the adipose tissue, were repressed ( P < 0.05) at L1. Our results illustrate that MEC exhibit dynamic molecular plasticity during the nonsecretory to secretory transition and increase biosynthetic capacity through a coordinated tissue specific SLC transcriptome modification to facilitate substrate transfer.

Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle

“…We focused on SLC membrane transport proteins because they are the largest group of transporters that import and export most nutrients, such as sugars, SCFAs, and amino acids [70] . SLCs are ubiquitously distributed throughout tissues, and those associated with metabolic homeostasis are indispensable for supporting lactation [71] . Instead of glucose, the SCFAs released as the major end products of microbial fermentation in the reticulorumen are absorbed through the epithelium as a major energy source in dairy cattle [31] , [35] .…”

Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis

“…Also among the BMAL1 targets were a multitude of ion transporters, solute carriers, glutamate transporters and ATP-binding cassette transporters. Synthesis and secretion of milk is dependent on membrane transport systems that move ions and substrates into and out of epithelial cells [35,36]. Movement of ions by ion transporters creates potential differences that enable electrical signaling which regulates cell number, shape, differentiation, and morphogenesis [37].…”

A Comparative Review of the Cell Biology, Biochemistry, and Genetics of Lactose Synthesis

“…In humans, GLUT1 increased 1.4-fold between 6 h and L(7) in MEC, while GLUT1 and GLUT10 increased 7 and 8-fold, respectively, by L(4) from 6 h postpartum [48]. In mice and rats, GLUT1 gene expression increased approximately 3-fold by L(2) relative to that in late gestation [125,126]. Even though these data confirm a well-established increase in GLUT1 gene and protein expression in MEC around secretory activation, there is no clear consensus as to the level of GLUT1 gene expression required for maximal lactose synthesis [30].…”

“…The expression of SLC35A2 increased 1.88-fold by L (14) and then decreased by L(21), while the protein expression of SLC35A2 increased by L(4) and then plateaued [49]. In lactating rats, the Hk1 gene was expressed in mammary tissue samples from both pregnant and lactating rats, whereas Hk2 was expressed only during lactation after its expression increased 2.44-fold by L(1.5) [126,127].…”