Department of Pharmacology, School of Medical Sciences, UNSW Sydney NSW 2052, Australia.
Department of Genetics, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.
Cells. 2020 Mar 25;9(4):791. doi: 10.3390/cells9040791.
Maternal obesity impacts offspring metabolism. We sought to boost mitochondrial energy metabolism using the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide (NMN) to treat metabolic impairment induced by maternal and long-term post weaning over-nutrition. Male offspring of lean or obese mothers, fed chow or high fat diet (HFD) for 30 weeks post-weaning, were given NMN injection, starting at 31 weeks of age, daily for 3 weeks before sacrifice. Glucose tolerance was tested at 10, 29 and 32 weeks of age to measure short and long term effects of post-weaning HFD, and NMN treatment. Plasma insulin and triglycerides, liver triglycerides and expression of mitochondrial metabolism-related genes were measured at 34 weeks. Impaired glucose tolerance due to maternal and post weaning HFD was significantly improved by only 8 days of NMN treatment. Furthermore, in offspring of obese mothers hepatic lipid accumulation was reduced due to NMN treatment by 50% and 23% in chow and HFD fed offspring respectively. Hepatic genes involved in fat synthesis, transport and uptake were reduced, while those involved in fatty acid oxidation were increased by NMN. Overall this finding suggests short term administration of NMN could be a therapeutic approach for treating metabolic disease due to maternal and post weaning over-nutrition, even in late adulthood.
母体肥胖会影响后代的新陈代谢。我们试图通过使用烟酰胺腺嘌呤二核苷酸（NAD）前体烟酰胺单核苷酸（NMN）来提高线粒体能量代谢，以治疗由母体和长期断奶后过度营养引起的代谢障碍。瘦母鼠或肥胖母鼠的雄性后代，在断奶后 30 周给予标准饮食（chow）或高脂肪饮食（HFD），从 31 周龄开始给予 NMN 注射，每天一次，持续 3 周，然后处死。在 10、29 和 32 周龄时测试葡萄糖耐量，以测量断奶后 HFD 和 NMN 治疗的短期和长期影响。在 34 周时测量血浆胰岛素和甘油三酯、肝脏甘油三酯和线粒体代谢相关基因的表达。仅 8 天的 NMN 治疗即可显著改善由母体和断奶后 HFD 引起的葡萄糖耐量受损。此外，由于 NMN 治疗，肥胖母鼠后代的肝脏脂质积累分别减少了 50%和 23%，在 chow 和 HFD 喂养的后代中。NMN 增加了参与脂肪酸氧化的基因，同时减少了参与脂肪合成、转运和摄取的基因。总的来说，这一发现表明，短期给予 NMN 可能是治疗由母体和断奶后过度营养引起的代谢疾病的一种治疗方法，即使在成年后期也是如此。
