Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice
Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Thus far, hepatic Nampt has not been extensively explored in terms of its effects on serum lipid stability and liver lipids metabolism. In this s...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/4/568 |
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| author | Dao-Xin Wang Sheng-Li Qing Zhu-Wei Miao Heng-Yu Luo Jia-Sheng Tian Xiu-Ping Zhang Shu-Na Wang Tian-Guang Zhang Chao-Yu Miao |
| author_facet | Dao-Xin Wang Sheng-Li Qing Zhu-Wei Miao Heng-Yu Luo Jia-Sheng Tian Xiu-Ping Zhang Shu-Na Wang Tian-Guang Zhang Chao-Yu Miao |
| author_sort | Dao-Xin Wang |
| collection | DOAJ |
| description | Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Thus far, hepatic Nampt has not been extensively explored in terms of its effects on serum lipid stability and liver lipids metabolism. In this study, hepatocyte-specific Nampt knockout (HC-Nampt<sup>-/-</sup>) mice were generated by Cre/loxP system. Nampt mRNA expression was reduced in the liver, but not in other tissues, in HC-Nampt<sup>-/-</sup> mice compared with wild-type (WT) mice. Hepatic Nampt deficiency had no effect on body weight and fasting blood glucose, and it did not induce atherosclerosis in mice under both normal chow diet (NCD) and high fat diet (HFD). At baseline state under NCD, hepatic Nampt deficiency also did not affect liver weight, liver function index, including alanine aminotransferase, aspartate aminotransferase, albumin and alkaline phosphatase, and serum levels of lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA). However, under HFD, deficiency of hepatic Nampt resulted in increased liver weight, liver function index, and serum levels of TG, TC, HDL-C, and NEFA. Meanwhile, histopathological examination showed increased fat accumulation and fibrosis in the liver of HC-Nampt<sup>-/-</sup> mice compared with WT mice. Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver. |
| first_indexed | 2024-03-11T09:00:57Z |
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| last_indexed | 2024-03-11T09:00:57Z |
| publishDate | 2023-02-01 |
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| series | Cells |
| spelling | doaj.art-7d43a471f5244914a41b964957ef55cc2023-11-16T19:44:09ZengMDPI AGCells2073-44092023-02-0112456810.3390/cells12040568Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed MiceDao-Xin Wang0Sheng-Li Qing1Zhu-Wei Miao2Heng-Yu Luo3Jia-Sheng Tian4Xiu-Ping Zhang5Shu-Na Wang6Tian-Guang Zhang7Chao-Yu Miao8Department 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, 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, ChinaNicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Thus far, hepatic Nampt has not been extensively explored in terms of its effects on serum lipid stability and liver lipids metabolism. In this study, hepatocyte-specific Nampt knockout (HC-Nampt<sup>-/-</sup>) mice were generated by Cre/loxP system. Nampt mRNA expression was reduced in the liver, but not in other tissues, in HC-Nampt<sup>-/-</sup> mice compared with wild-type (WT) mice. Hepatic Nampt deficiency had no effect on body weight and fasting blood glucose, and it did not induce atherosclerosis in mice under both normal chow diet (NCD) and high fat diet (HFD). At baseline state under NCD, hepatic Nampt deficiency also did not affect liver weight, liver function index, including alanine aminotransferase, aspartate aminotransferase, albumin and alkaline phosphatase, and serum levels of lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA). However, under HFD, deficiency of hepatic Nampt resulted in increased liver weight, liver function index, and serum levels of TG, TC, HDL-C, and NEFA. Meanwhile, histopathological examination showed increased fat accumulation and fibrosis in the liver of HC-Nampt<sup>-/-</sup> mice compared with WT mice. Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.https://www.mdpi.com/2073-4409/12/4/568Namptdyslipidemiaserum lipidsfatty liverhepatopathyhepatocyte |
| spellingShingle | Dao-Xin Wang Sheng-Li Qing Zhu-Wei Miao Heng-Yu Luo Jia-Sheng Tian Xiu-Ping Zhang Shu-Na Wang Tian-Guang Zhang Chao-Yu Miao Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice Cells Nampt dyslipidemia serum lipids fatty liver hepatopathy hepatocyte |
| title | Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice |
| title_full | Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice |
| title_fullStr | Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice |
| title_full_unstemmed | Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice |
| title_short | Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice |
| title_sort | hepatic nampt deficiency aggravates dyslipidemia and fatty liver in high fat diet fed mice |
| topic | Nampt dyslipidemia serum lipids fatty liver hepatopathy hepatocyte |
| url | https://www.mdpi.com/2073-4409/12/4/568 |
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