Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice

Background & Aims Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. H...

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Main Authors: Xue Han, Xiaogang Bao, Qi Lou, Xian Xie, Meng Zhang, Shasang Zhou, Honggang Guo, Guojun Jiang, Qiaojuan Shi
Format: Article
Language:English
Published: PeerJ Inc. 2019-08-01
Series:PeerJ
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Online Access:https://peerj.com/articles/7568.pdf
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author Xue Han
Xiaogang Bao
Qi Lou
Xian Xie
Meng Zhang
Shasang Zhou
Honggang Guo
Guojun Jiang
Qiaojuan Shi
author_facet Xue Han
Xiaogang Bao
Qi Lou
Xian Xie
Meng Zhang
Shasang Zhou
Honggang Guo
Guojun Jiang
Qiaojuan Shi
author_sort Xue Han
collection DOAJ
description Background & Aims Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD. Methods NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammatory infiltration. Results NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Conclusion Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.
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spelling doaj.art-8433926a6d79430f9d236d699cd047172023-12-03T10:26:04ZengPeerJ Inc.PeerJ2167-83592019-08-017e756810.7717/peerj.7568Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in miceXue Han0Xiaogang Bao1Qi Lou2Xian Xie3Meng Zhang4Shasang Zhou5Honggang Guo6Guojun Jiang7Qiaojuan Shi8Laboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaDepartment of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaLaboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaHospital of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, ChinaLaboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaLaboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaZhejiang Xiaoshan Hospital, Hangzhou, Zhejiang Province, ChinaLaboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaBackground & Aims Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD. Methods NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammatory infiltration. Results NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Conclusion Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.https://peerj.com/articles/7568.pdfNon-alcoholic fatty liver diseaseNicotinamide adenine dinucleotideNicotinamide ribosideAged miceInflammatory infiltration
spellingShingle Xue Han
Xiaogang Bao
Qi Lou
Xian Xie
Meng Zhang
Shasang Zhou
Honggang Guo
Guojun Jiang
Qiaojuan Shi
Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
PeerJ
Non-alcoholic fatty liver disease
Nicotinamide adenine dinucleotide
Nicotinamide riboside
Aged mice
Inflammatory infiltration
title Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
title_full Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
title_fullStr Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
title_full_unstemmed Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
title_short Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
title_sort nicotinamide riboside exerts protective effect against aging induced nafld like hepatic dysfunction in mice
topic Non-alcoholic fatty liver disease
Nicotinamide adenine dinucleotide
Nicotinamide riboside
Aged mice
Inflammatory infiltration
url https://peerj.com/articles/7568.pdf
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