期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 473, 期 -, 页码 245-256出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2018.01.025
关键词
NAD(+) salvage pathways; NAFLD; SIRT5; lysine malonylation; High-fat diet; C57BL/6JBomTac
资金
- Novo Nordisk Foundation [NNF14OC0009315]
- Danish Council for Independent Research [DFF 4004-00235]
- Novo Nordisk Foundation Center for Basic Metabolic Research (NNF-CBMR)
- Novo Nordisk Foundation
- Danish Diabetes Academy - Novo Nordisk Foundation
- European Foundation for the Study of Diabetes (EFSD) Albert Renold Travel Fellowship Programme
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [705869]
- Marie Curie Actions (MSCA) [705869] Funding Source: Marie Curie Actions (MSCA)
Dietary supplementation of nicotinamide adenine dinucleotide (NAD(+)) precursors has been suggested as a treatment for non-alcoholic fatty liver disease and obesity. In the liver, NAD(+) is primarily generated by nicotinamide phosphoribosyltransferase (NAMPT), and hepatic levels of NAMPT and NAD(+) have been reported to be dependent on age and body composition. The aim of the present study was to identify time course-dependent changes in hepatic NAD content and NAD(+) salvage capacity in mice challenged with a high-fat diet (HFD). We fed 7-week-old C57BL/6JBomTac male mice either regular chow or a 60% HFD for 6, 12, 24, and 48 weeks, and we evaluated time course-dependent changes in whole body metabolism, liver steatosis, and abundance of hepatic NAD-associated metabolites and enzymes. Mice fed a 60% HFD rapidly accumulated fat and hepatic triglycerides with associated changes in respiratory exchange ratio (RER) and a disruption of the circadian feeding pattern. The HFD did not alter hepatic NAD(+) levels, but caused a decrease in NADP(+) and NADPH levels. Decreased NADP(+) content was not accompanied by alterations in NAD kinase (NADK) abundance in HFD-fed mice, but NADK levels increased with age regardless of diet. NAMPT protein abundance did not change with age or diet. HFD consumption caused a severe decrease in protein lysine malonylation after six weeks, which persisted throughout the experiment. This decrease was not associated with changes in SIRT5 abundance. In conclusion, hepatic NAD(+) salvage capacity is resistant to long-term HFD feeding, and hepatic lipid accumulation does not compromise the hepatic NAD(+) pool in HFD-challenged C57BL/6JBomTac male mice. (C) 2018 Elsevier B.V. All rights reserved.
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