Nicotinamide N-methyltransferase and liver diseases
Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular homeostasis. Nicotinamide N-methyltransferase (NNMT) is emerging as a key point of intersection between cellular metabolism and epigenetic regulation and has a central role in various physiological and pat...
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KeAi Communications Co., Ltd.
2023-09-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304222000952 |
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| author | Guangyu Liang Ying Li Yan Lin Xiao Yang Jiankun Yang Shaobo Hu Anding Liu |
| author_facet | Guangyu Liang Ying Li Yan Lin Xiao Yang Jiankun Yang Shaobo Hu Anding Liu |
| author_sort | Guangyu Liang |
| collection | DOAJ |
| description | Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular homeostasis. Nicotinamide N-methyltransferase (NNMT) is emerging as a key point of intersection between cellular metabolism and epigenetic regulation and has a central role in various physiological and pathological processes. NNMT catalyzes the methylation of nicotinamide (NAM) using the universal methyl donor S-adenosyl methionine (SAM) to yield S-adeno-syl-L-homocysteine (SAH) and N1-methylnicotinamide (MNAM), directly linking methylation balance with nicotinamide adenosine dinucleotide (NAD+) contents. NNMT acts on either the SAM-methylation balance or both NAD+ metabolism, depending on the tissue involved or pathological settings where metabolic demand is increased. Under physiological conditions, the liver act as an essential metabolic organ with abundant NNMT expression, while NNMT hepatic function is not mediated by its methyltransferase activity due to other major methyltransferases such as glycine N-methyltransferase (GNMT) in the liver. However, hepatic NNMT, as well as its metabolite is improperly regulated and linked to the worse pathological states in liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and hepatocellular carcinoma (HCC), suggesting a potential role in the process of liver diseases. In this review, we summarize how NNMT regulates cell methylation balance and NAD metabolism, and extensively outline the current knowledge concerning the functions of NNMT in hepatic metabolism including glucose, lipid and energy, with a specific focus on the contribution of NNMT to the pathophysiology of liver-related diseases. NNMT is involved in the development and progression of liver diseases. Understanding the complex NNMT regulatory network and its effects on pathogenesis could provide new therapeutic strategies in the context of liver diseases. |
| first_indexed | 2024-03-13T00:14:55Z |
| format | Article |
| id | doaj.art-da5f4cb80f3f4e839ceb322fd2a50eba |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-13T00:14:55Z |
| publishDate | 2023-09-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj.art-da5f4cb80f3f4e839ceb322fd2a50eba2023-07-12T04:19:34ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-09-0110518831893Nicotinamide N-methyltransferase and liver diseasesGuangyu Liang0Ying Li1Yan Lin2Xiao Yang3Jiankun Yang4Shaobo Hu5Anding Liu6Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaExperimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaExperimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaExperimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaExperimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Corresponding author. Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei 430030, China.Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Corresponding author. Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China.Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular homeostasis. Nicotinamide N-methyltransferase (NNMT) is emerging as a key point of intersection between cellular metabolism and epigenetic regulation and has a central role in various physiological and pathological processes. NNMT catalyzes the methylation of nicotinamide (NAM) using the universal methyl donor S-adenosyl methionine (SAM) to yield S-adeno-syl-L-homocysteine (SAH) and N1-methylnicotinamide (MNAM), directly linking methylation balance with nicotinamide adenosine dinucleotide (NAD+) contents. NNMT acts on either the SAM-methylation balance or both NAD+ metabolism, depending on the tissue involved or pathological settings where metabolic demand is increased. Under physiological conditions, the liver act as an essential metabolic organ with abundant NNMT expression, while NNMT hepatic function is not mediated by its methyltransferase activity due to other major methyltransferases such as glycine N-methyltransferase (GNMT) in the liver. However, hepatic NNMT, as well as its metabolite is improperly regulated and linked to the worse pathological states in liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and hepatocellular carcinoma (HCC), suggesting a potential role in the process of liver diseases. In this review, we summarize how NNMT regulates cell methylation balance and NAD metabolism, and extensively outline the current knowledge concerning the functions of NNMT in hepatic metabolism including glucose, lipid and energy, with a specific focus on the contribution of NNMT to the pathophysiology of liver-related diseases. NNMT is involved in the development and progression of liver diseases. Understanding the complex NNMT regulatory network and its effects on pathogenesis could provide new therapeutic strategies in the context of liver diseases.http://www.sciencedirect.com/science/article/pii/S2352304222000952EpigeneticsLiver diseasesMetabolismNicotinamide N-methyltransferaseNon-alcoholic fatty liver disease |
| spellingShingle | Guangyu Liang Ying Li Yan Lin Xiao Yang Jiankun Yang Shaobo Hu Anding Liu Nicotinamide N-methyltransferase and liver diseases Genes and Diseases Epigenetics Liver diseases Metabolism Nicotinamide N-methyltransferase Non-alcoholic fatty liver disease |
| title | Nicotinamide N-methyltransferase and liver diseases |
| title_full | Nicotinamide N-methyltransferase and liver diseases |
| title_fullStr | Nicotinamide N-methyltransferase and liver diseases |
| title_full_unstemmed | Nicotinamide N-methyltransferase and liver diseases |
| title_short | Nicotinamide N-methyltransferase and liver diseases |
| title_sort | nicotinamide n methyltransferase and liver diseases |
| topic | Epigenetics Liver diseases Metabolism Nicotinamide N-methyltransferase Non-alcoholic fatty liver disease |
| url | http://www.sciencedirect.com/science/article/pii/S2352304222000952 |
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