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Biochem Biophys Res Commun. 2018 Jun 2;500(2):476-483. doi: 10.1016/j.bbrc.2018.04.107.

Overexpression of NRK1 ameliorates diet- and age-induced hepatic steatosis and insulin resistance.

Author information

1
School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
2
School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China; Laboratory of Molecular Metabolism, Xinxiang Medical University, Xinxiang, Henan, China.
3
School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
4
School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China. Electronic address: qxlfssws@163.com.
5
School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China; Laboratory of Molecular Metabolism, Xinxiang Medical University, Xinxiang, Henan, China. Electronic address: xwxiong@xxmu.edu.cn.

Abstract

NAD+ is a co-enzyme in redox reactions and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we sought to identify the roles of nicotinamide riboside kinase 1 (NRK1) plays in regulating hepatic NAD+ biosynthesis and lipid metabolism. Using adenovirus mediated gene transduction to overexpress or knockdown NRK1 in mouse liver, we have demonstrated that NRK1 is critical for maintaining hepatic NAD+ levels and triglyceride content. We have further shown that the hepatic expression of Nmrk1 mRNA is significantly decreased either in mice treated with high-fat diet or in aged mice. However, adenoviral delivery of NRK1 in these diet- and age-induced mice elevates hepatic NAD+ levels, reduces hepatic steatosis, and improves glucose tolerance and insulin sensitivity. Our results provide important insights in targeting NRK1 for treating hepatic steatosis.

KEYWORDS:

Hepatic steatosis; Insulin resistance; NAD(+); NRK1

PMID:
29678570
DOI:
10.1016/j.bbrc.2018.04.107
[Indexed for MEDLINE]

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