NAD⁺ Repletion Enhances Mammary Lactogenesis and Improves Offspring Development in a Sow Model

Area of Science:

• Reproductive Physiology
• Metabolic Biochemistry

Background:

• Lactation insufficiency is a clinical challenge due to poorly understood lactogenesis mechanisms.
• Nicotinamide adenine dinucleotide (NAD+) is emerging as a key regulator in reproductive physiology.

Purpose of the Study:

• To characterize mammary gland NAD+ metabolism.
• To evaluate the effect of maternal nicotinamide riboside (NR) supplementation on mammary lactogenesis.

Main Methods:

• Twenty sows were divided into control and NR supplementation groups (25 mg NR/kg body weight/d).
• Mammary gland biopsies, microdialysis, milk analysis, and offspring growth assessments were performed.
• Data were analyzed using t tests and 2-factor analysis of variance.

Main Results:

• NR supplementation significantly increased mammary and milk NAD+ levels, leading to a 31% increase in daily milk yield.
• NR enhanced mammary gland alveolar development and lactogenesis gene expression, improving offspring weaning weight by 23%.
• NAD+-SIRT1 signaling was activated, increasing mitochondrial density and biogenesis.

Conclusions:

• Maternal NR supplementation effectively meets the NAD+ demands of lactating mammary glands.
• NR potentiates mammary secretory differentiation and milk biosynthesis, offering therapeutic potential for lactation insufficiency.
• This study identifies novel biomarkers and therapeutic targets for improving lactation.