Effect of liver-specific NMNAT1 knockout on NAD + and overall metabolism in obese mice
10.3760/cma.j.cn311282-20250303-00113
- VernacularTitle:肝脏NMNAT1特异性敲除对肥胖小鼠NAD ＋及整体代谢的影响
- Author:
Kang DU
1
;
Weiying REN
1
;
Yu HU
1
Author Information
1. 复旦大学附属中山医院老年病科，上海 200032
- Publication Type:Journal Article
- Keywords:
Nicotinamide adenine dinucleotide;
Nicotinamide mononucleotide adenylyl transferase 1;
Liver;
Metabolism
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(8):656-663
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of nicotinamide nucleotide adenylyltransferase 1(NMNAT1) liver-specific knockout on nicotinamide adenine dinucleotide(NAD + ) and overall metabolism in obese mice. Methods:NMNAT1 fl/fl mice were injected with AAV8-TBG-CRE through the tail vein to produce NMNAT1 liver-specific knockout mice, which were fed with either chow diet or high-fat diet, and the body weight of the mice was measured weekly, followed by glucose tolerance test, insulin tolerance test, body composition analysis, metabolic cage test and related assays, and finally the mouse liver was taken for liquid chromatography-mass spectrometry to detect the changes of metabolites. The related metabolic pathways were analyzed by metabolic database enrichment. Results:There was no difference in body weight between NMNAT1 LKO mice and control mice, and the body composition measurement of mice by EchoMRI also showed no difference in fat mass and lean mass. Metabolic cage experiments showed that NMNAT1 LKO had no effect on oxygen consumption, carbon dioxide production, respiration exchange ratio, energy expenditure and other indexes in mice. The glucose tolerance test and insulin tolerance test showed that NMNAT1 LKO did not affect glucose tolerance and insulin sensitivity in mice. NMNAT1 LKO does not affect the content of triglycerides in the liver of obese mice. NAD + detection confirmed that NMNAT1 LKO reduced hepatic NAD + content of obese mice by approximately 50%, resulting in the increase and accumulation of the NMNAT1 substrates, i. e. nicotinamide mononucleotide(NMN) and nicotinic acid mononucleotide(NaMN). Conclusion:Liver-specific knockout of NMNAT1 significantly reduced the NAD + content and changed the NAD + metabolism in the liver of obese mice, but without altering the glucose, lipid or energy metabolism.
