Huang Long, Pan Chenglin, Zhang Wei, He Liu, Ma Lulu, Li Yingjie, Zhang Ruilan, Li Ying, Zhuo Yong, Jiang Xuemei, Che Lianqiang, Lin Yan, Xu Shengyu, Fang Zhengfeng, Feng Bin, Wu De, Hua Lun
Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China; Key Laboratory of Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, College of Life Science and Engineering, Foshan University, Foshan, China.
J Nutr. 2025 Jun 30. doi: 10.1016/j.tjnut.2025.06.013.
Breastfeeding provides bidirectional biosocial benefits for maternal-neonatal dyads, yet lactation insufficiency remains a major clinical challenge due to incomplete understanding of lactogenesis mechanisms. Emerging evidence has identified nicotinamide adenine dinucleotide (NAD+) as a critical modulator of reproductive physiology.
We characterized mammary gland (MG) NAD+ metabolism and evaluated maternal nicotinamide riboside (NR), an NAD+ precursor, supplementation in orchestrating mammary lactogenesis.
Twenty multiparous sows were randomly allocated into either a control group fed a basal diet (CON, n = 10) or an NR treatment group (NR, n = 10) that was administered 25 mg NR/kg body weight/d in split-feed doses. Sow MG biopsies obtained under local anesthesia were analyzed for NAD+ metabolites (NAD+ and NR), histology/ultrastructure, and lactogenesis genes. MG microenvironment glucose substances in vivo were monitored using microdialysis. Milk metabolomics/composition (fat and protein) and offspring growth rate, rectal temperature (after cold stress), and intestine function (after lipopolysaccharide challenge) were assessed. Data were analyzed using t tests and 2-factor analysis of variance.
About 17-fold NAD+ levels and NAD+ metabolic enzymes were increased in lactating MG (P < 0.05). NR upregulated mammary and milk NAD+ levels (+ 38% and + 256%, P < 0.05), alongside 31% more milk daily yield (18.0 compared with 13.7 kg, P < 0.05). NR increased MG alveolar lumen area (+46%) and lactogenesis genes (P < 0.05), paralleled by elevated pyruvate and lactate to glucose ratios (+53% and +157%) in microdialysis (P < 0.10). Offspring from NR group demonstrated 23% higher weaning weight (P < 0.05) with a reduction of hypothermia and gut barrier dysfunction (P < 0.05). Mechanistically, NAD-SIRT1 signaling increased mitochondrial density (+60%) and biogenesis indices (P < 0.05).
NR supplementation meets lactating mammary NAD demands, restoring NAD+ levels to potentiate secretory differentiation and milk biosynthesis, identifying novel biomarkers and therapeutic targets for lactation insufficiency.
母乳喂养对母婴二元组具有双向生物社会效益，但由于对泌乳机制的不完全理解，泌乳不足仍然是一个主要的临床挑战。新出现的证据表明烟酰胺腺嘌呤二核苷酸（NAD+）是生殖生理学的关键调节因子。
我们对乳腺（MG）的NAD+代谢进行了表征，并评估了母体烟酰胺核糖（NR）（一种NAD+前体）补充剂在协调乳腺泌乳中的作用。
将20头经产母猪随机分为两组，一组为喂食基础日粮的对照组（CON，n = 10），另一组为NR治疗组（NR，n = 10），NR治疗组以分饲剂量给予25 mg NR/（kg体重/天）。对在局部麻醉下获得的母猪MG活检组织进行NAD+代谢物（NAD+和NR）、组织学/超微结构和泌乳相关基因分析。使用微透析监测体内MG微环境中的葡萄糖物质。评估牛奶代谢组学/成分（脂肪和蛋白质）以及后代生长速率、直肠温度（冷应激后）和肠道功能（脂多糖攻击后）。数据采用t检验和双因素方差分析。
泌乳期MG中的NAD+水平和NAD+代谢酶增加了约17倍（P < 0.05）。NR上调了乳腺和牛奶中的NAD+水平（分别增加38%和256%，P < 0.05），同时日产奶量增加31%（18.0 kg比13.7 kg，P < 0.05）。NR增加了MG腺泡腔面积（增加46%）和泌乳相关基因（P < 0.05），微透析中丙酮酸和乳酸与葡萄糖的比率升高（分别增加53%和157%，P < 0.10）与之平行。NR组的后代断奶体重高出23%（P < 0.05），体温过低和肠道屏障功能障碍有所减轻（P < 0.05）。从机制上讲，NAD-SIRT1信号通路增加了线粒体密度（增加60%）和生物发生指数（P < 0.05）。
补充NR可满足泌乳期乳腺对NAD的需求，恢复NAD+水平以增强分泌分化和乳汁生物合成，为泌乳不足确定了新的生物标志物和治疗靶点。
