AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

Abstract

Background: The local supply of energy-yielding nutrients such as glucose seems to affect the synthesis of milk components in the mammary gland (MG). Thus, our study was conducted to investigate the effects of locally available MG glucose supply (LMGS) on amino acid (AA) sensing and utilization in the MG of lactating dairy goats. Six dosages of glucose (0, 20, 40, 60, 80, and 100 g/d) were infused into the MG through the external pudendal artery to investigate the dose-dependent changes in mammary AA uptake and utilization (Exp.1) and the changes in mRNA and protein expression of the AMPK-mTOR pathway (Expt.2). Results: In Exp.1, total milk AA concentration was highest when goats were infused with 60 g/d glucose, but lower when goats were infused with 0 and 100 g/d glucose. Increasing LMGS quadratically changed the percentages of α S2-casein and α-lactalbumin in milk protein, which increased with infusions from 0 to 60 g/d glucose and then decreased with infusions between 60 and 100 g/d glucose. The LMGS changed the AA availability and intramammary gland AA utilization, as reflected by the mammary AA flux indexes. In Exp.2, the mRNA expression of LALBA in the MG increased quadratically with increasing LMGS, with the highest expression at dose of 60 g/d glucose. A high glucose dosage (100 g/d) activated the general control nonderepressible 2 kinase, an intracellular sensor of AA status, resulting in a reduced total milk AA concentration. Conclusions: Our new findings suggest that the lactating MG in dairy goats may be affected by LMGS through regulation of the AA sensory pathway, AA utilization and protein synthesis, all being driven by the AMPK-mTOR pathway.

SNPs in Mammary Gland Epithelial Cells Unraveling Potential Difference in Milk Production Between Jersey and Kashmiri Cattle Using RNA Sequencing

“…This statement however, needs to be validated. Similar studies were reported in lactating goats (Cai et al, 2020).…”

Mutation of Signal Transducer and Activator of Transcription 5 (STAT5) Binding Sites Decreases Milk Allergen αS1-Casein Content in Goat Mammary Epithelial Cells

“…After the knockout of STAT5 in the mouse mammary gland, the content of α-lactalbumin and β-lactoglobulin in milk was reduced by 23% and 39%, respectively [15]. In addition to STAT5, mammalian target of rapamycin (mTOR) also regulates the synthesis of milk proteins such as α-lactalbumin and α S1 -casein [44,45]. In bovine mammary epithelial cells, suppressor of cytokine signaling 3 inhibited STAT5a activity, and milk protein synthesis was significantly reduced after the phosphorylation of STAT5a was blocked [46,47].…”

Mitochondria as a therapeutic target for cardiac ischemia‑reperfusion injury (Review)

“…Attention must be paid to mitophagy, which is a complex process and intersects with several other cellular events. Some mediators in mitophagy signaling pathways, such as mTOR and AMPK, also play roles in mitochondrial biogenesis ( 19 , 66 ), intrinsic fatty acid metabolism ( 141 ), glucose-modulated amino acid sensing and utilization ( 142 ), endothelium-dependent vasodilation in vessels ( 143 ), vascular smooth muscle cell proliferation and migration ( 144 ), suggesting that the manipulation of these may cause a series of unexpected side-effects.…”