NAMPT reduction‐induced NAD+ insufficiency contributes to the compromised oocyte quality from obese mice |
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Authors: | Hengjie Wang Shuai Zhu Xinghan Wu Yuan Liu Juan Ge Qiang Wang Ling Gu |
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Institution: | 1. College of Animal Science & Technology, Nanjing Agricultural University, Nanjing China ; 2. State Key Laboratory of Reproductive Medicine, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing China ; 3. Department of Medical Genetics, Maternal and Child Health Hospital of Hunan Province, Changsha China |
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Abstract: | Maternal obesity is associated with multiple adverse reproductive outcomes, whereas the underlying molecular mechanisms are still not fully understood. Here, we found the reduced nicotinamide phosphoribosyl transferase (NAMPT) expression and lowered nicotinamide adenine dinucleotide (NAD+) content in oocytes from obese mice. Next, by performing morpholino knockdown assay and pharmacological inhibition, we revealed that NAMPT deficiency not only severely disrupts maturational progression and meiotic apparatus, but also induces the metabolic dysfunction in oocytes. Furthermore, overexpression analysis demonstrated that NAMPT insufficiency induced NAD+ loss contributes to the compromised developmental potential of oocytes and early embryos from obese mice. Importantly, in vitro supplement and in vivo administration of nicotinic acid (NA) was able to ameliorate the obesity‐associated meiotic defects and oxidative stress in oocytes. Our results indicate a role of NAMPT in modulating oocyte meiosis and metabolism, and uncover the beneficial effects of NA treatment on oocyte quality from obese mice. |
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Keywords: | meiosis metabolism nicotinamide phosphoribosyl transferase obesity oocyte |
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