Le Huyen, Nguyen Mai, Manso Helena Emilia Ccc, Wang Michelle D, Watford Malcolm
Department of Nutritional Sciences, Rutgers-The State University of New Jersey, New Brunswick, NJ, United States.
Rutgers Center for Lipid Research, Rutgers-The State University of New Jersey, New Brunswick, NJ, United States.
Curr Dev Nutr. 2024 Apr 23;8(6):102168. doi: 10.1016/j.cdnut.2024.102168. eCollection 2024 Jun.
Glutamine in milk is believed to play an important role in neonatal intestinal maturation and immune function. For lactating mothers, glutamine utilization is increased to meet the demands of the enlarged intestine and milk production. However, the source of such glutamine during lactation has not been studied.
We aimed to assess the effects of lactation on the expression of glutamine synthetase (GS) in the mammary gland and other tissues of lactating mice.
Mouse tissues were sampled at 4 time points: 8-wk-old (virgin, control), post-delivery day 5 (PD5, early lactation), PD15 (peak lactation), and involution (4 days after weaning at PD21). We examined the gene expression and protein concentrations of GS and the first 2 enzymes of branched-chain amino acid catabolism: branched-chain aminotransferase 2 (BCAT2) and branched-chain ketoacid dehydrogenase subunit E1α (BCKDHA).
The messenger RNA (mRNA) expression and protein concentrations of GS in mammary glands were significantly lower at PD5 and PD15 compared with the control but were restored at involution. Within the mammary gland, GS protein was only detected in adipocytes with no evidence of presence in mammary epithelial cells. Compared with the control, mRNA and protein concentrations of BCAT2 and BCKDHA in mammary glands significantly decreased during lactation and involution. No changes in GS protein concentrations during lactation were found in the liver, skeletal muscle, and lung. In non-mammary adipose tissue, GS protein abundance was higher during lactation compared with the virgin.
This work shows that, within the mouse mammary gland, GS is only expressed in adipocytes and that the relative GS abundance in mammary gland sections is lower during lactation. This suggests that mammary adipocytes may be a site of glutamine synthesis in the lactating mouse. Identifying the sources of glutamine production during lactation is important for optimizing milk glutamine concentration to enhance neonatal and maternal health.
牛奶中的谷氨酰胺被认为在新生儿肠道成熟和免疫功能中发挥重要作用。对于哺乳期母亲,谷氨酰胺的利用增加以满足扩大的肠道和乳汁生成的需求。然而,哺乳期这种谷氨酰胺的来源尚未得到研究。
我们旨在评估哺乳对哺乳期小鼠乳腺及其他组织中谷氨酰胺合成酶(GS)表达的影响。
在4个时间点采集小鼠组织:8周龄(未生育,对照)、分娩后第5天(PD5,哺乳早期)、PD15(泌乳高峰期)和退化期(PD21断奶后4天)。我们检测了GS以及支链氨基酸分解代谢的前两种酶的基因表达和蛋白质浓度:支链氨基转移酶2(BCAT2)和支链酮酸脱氢酶亚基E1α(BCKDHA)。
与对照组相比,PD5和PD15时乳腺中GS的信使核糖核酸(mRNA)表达和蛋白质浓度显著降低,但在退化期恢复。在乳腺内,仅在脂肪细胞中检测到GS蛋白,没有证据表明其存在于乳腺上皮细胞中。与对照组相比,哺乳期和退化期乳腺中BCAT2和BCKDHA的mRNA和蛋白质浓度显著降低。哺乳期肝脏、骨骼肌和肺中GS蛋白浓度未发现变化。在非乳腺脂肪组织中,哺乳期GS蛋白丰度高于未生育小鼠。
这项研究表明,在小鼠乳腺内,GS仅在脂肪细胞中表达,且哺乳期乳腺切片中GS的相对丰度较低。这表明乳腺脂肪细胞可能是哺乳期小鼠谷氨酰胺合成的场所。确定哺乳期谷氨酰胺产生的来源对于优化乳汁谷氨酰胺浓度以增强新生儿和母亲健康很重要。