Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice

<b>Background:</b> Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are intermediary products in NAD+ metabolism. NMN and NR supplementation can elevate NAD+ levels in tissues, addressing health issues associated with aging and obesity. However, the impact of NMN and NR o...

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Main Authors: Pin Wang, Jia-Xin Li, Yuan-Yuan Kong, Si-Li Zheng, Chao-Yu Miao
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/3/281
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author Pin Wang
Jia-Xin Li
Yuan-Yuan Kong
Si-Li Zheng
Chao-Yu Miao
author_facet Pin Wang
Jia-Xin Li
Yuan-Yuan Kong
Si-Li Zheng
Chao-Yu Miao
author_sort Pin Wang
collection DOAJ
description <b>Background:</b> Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are intermediary products in NAD+ metabolism. NMN and NR supplementation can elevate NAD+ levels in tissues, addressing health issues associated with aging and obesity. However, the impact of NMN and NR on atherosclerosis remains incompletely elucidated. <b>Methods:</b> C57BL/6J and Apolipoprotein E knockout (ApoE<sup>−/−</sup>) mice were used to explore the impact of NMN and NR supplementation on serum lipids, fatty liver, and atherosclerosis. Additionally, various suppliers, administration protocols, and doses on ApoE<sup>−/−</sup> mice were investigated. <b>Results:</b> The intragastric administration of NMN (300 mg/kg) and NR (230 mg/kg) reduced body weight, serum lipids, and fatty liver but aggravated atherosclerosis in ApoE<sup>−/−</sup> mice after 4 months of administration with different suppliers. Atherosclerosis also deteriorated after 2 months of different NMN administration protocols (intragastric and water administration) in ApoE<sup>−/−</sup> mice with existing plaques. The effects of NMN were dose-dependent, and doses around 100 mg/kg had little harmful effects on atherosclerosis. <b>Conclusions:</b> NMN and NR improve dyslipidemia and fatty liver but promote atherosclerosis in ApoE<sup>−/−</sup> mice. These findings emphasize the safe dosage for the clinical trials of NMN.
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spelling doaj-art-07e74c0765b1494a8ae00221a4e51d442025-08-20T01:48:45ZengMDPI AGPharmaceuticals1424-82472025-02-0118328110.3390/ph18030281Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout MicePin Wang0Jia-Xin Li1Yuan-Yuan Kong2Si-Li Zheng3Chao-Yu Miao4Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, ChinaDepartment of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, ChinaDepartment of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, ChinaDepartment of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, ChinaDepartment of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, China<b>Background:</b> Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are intermediary products in NAD+ metabolism. NMN and NR supplementation can elevate NAD+ levels in tissues, addressing health issues associated with aging and obesity. However, the impact of NMN and NR on atherosclerosis remains incompletely elucidated. <b>Methods:</b> C57BL/6J and Apolipoprotein E knockout (ApoE<sup>−/−</sup>) mice were used to explore the impact of NMN and NR supplementation on serum lipids, fatty liver, and atherosclerosis. Additionally, various suppliers, administration protocols, and doses on ApoE<sup>−/−</sup> mice were investigated. <b>Results:</b> The intragastric administration of NMN (300 mg/kg) and NR (230 mg/kg) reduced body weight, serum lipids, and fatty liver but aggravated atherosclerosis in ApoE<sup>−/−</sup> mice after 4 months of administration with different suppliers. Atherosclerosis also deteriorated after 2 months of different NMN administration protocols (intragastric and water administration) in ApoE<sup>−/−</sup> mice with existing plaques. The effects of NMN were dose-dependent, and doses around 100 mg/kg had little harmful effects on atherosclerosis. <b>Conclusions:</b> NMN and NR improve dyslipidemia and fatty liver but promote atherosclerosis in ApoE<sup>−/−</sup> mice. These findings emphasize the safe dosage for the clinical trials of NMN.https://www.mdpi.com/1424-8247/18/3/281nicotinamide mononucleotidenicotinamide ribosideApoE knockout micefatty liveratherosclerosis
spellingShingle Pin Wang
Jia-Xin Li
Yuan-Yuan Kong
Si-Li Zheng
Chao-Yu Miao
Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
Pharmaceuticals
nicotinamide mononucleotide
nicotinamide riboside
ApoE knockout mice
fatty liver
atherosclerosis
title Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
title_full Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
title_fullStr Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
title_full_unstemmed Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
title_short Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
title_sort nicotinamide mononucleotide and nicotinamide riboside improve dyslipidemia and fatty liver but promote atherosclerosis in apolipoprotein e knockout mice
topic nicotinamide mononucleotide
nicotinamide riboside
ApoE knockout mice
fatty liver
atherosclerosis
url https://www.mdpi.com/1424-8247/18/3/281
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