The Journal of nutrition · 2025
NAD+ Repletion Enhances Mammary Lactogenesis and Improves Offspring Development in a Sow Model.
СтатьяНазвание и аннотация: Перевод в очереди
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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
Аннотация
BACKGROUND: 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.
OBJECTIVES: We characterized mammary gland (MG) NAD+ metabolism and evaluated maternal nicotinamide riboside (NR), an NAD+ precursor, supplementation in orchestrating mammary lactogenesis.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
OBJECTIVES: We characterized mammary gland (MG) NAD+ metabolism and evaluated maternal nicotinamide riboside (NR), an NAD+ precursor, supplementation in orchestrating mammary lactogenesis.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.