TY - JOUR
T1 - Hepatic NAD + levels and NAMPT abundance are unaffected during prolonged high-fat diet consumption in C57BL/6JBomTac mice
AU - Dall, Morten
AU - Penke, Melanie
AU - Sulek, Karolina
AU - Matz-Soja, Madlen
AU - Holst, Birgitte
AU - Garten, Antje
AU - Kiess, Wieland
AU - Treebak, Jonas T.
N1 - Funding Information:
The authors acknowledge the skilled technical assistance provided by Steve Risis, Søren Madsen, and Andreas Nygaard Madsen from the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, by Doris Mahn from the Rudolf-Schönheimer-Institute of Biochemistry, University of Leipzig, and by Anja Barnikol-Oettler and Sandy Richter from the Center for Pediatric Research, University Children's Hospital Leipzig.
Funding Information:
This work was funded in part by grants obtained by JTT from the Novo Nordisk Foundation (Excellence Project Award, NNF14OC0009315), and the Danish Council for Independent Research (DFF 4004-00235). Moreover, support for this study was also provided by the Novo Nordisk Foundation Center for Basic Metabolic Research (NNF-CBMR). NNF-CBMR is an independent Research Center at the University of Copenhagen and partially funded by an unrestricted donation from the Novo Nordisk Foundation, (http://metabol.ku.dk). MD was supported by a 1/3 PhD stipend from the Danish Diabetes Academy, funded by the Novo Nordisk Foundation. Support for this project was also provided by the European Foundation for the Study of Diabetes (EFSD) Albert Renold Travel Fellowship Programme (to MP), and from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 705869 (to AG).
Funding Information:
This work was funded in part by grants obtained by JTT from the Novo Nordisk Foundation (Excellence Project Award, NNF14OC0009315 ), and the Danish Council for Independent Research ( DFF 4004-00235 ). Moreover, support for this study was also provided by the Novo Nordisk Foundation Center for Basic Metabolic Research (NNF-CBMR) . NNF-CBMR is an independent Research Center at the University of Copenhagen and partially funded by an unrestricted donation from the Novo Nordisk Foundation , ( http://metabol.ku.dk ). MD was supported by a 1/3 PhD stipend from the Danish Diabetes Academy, funded by the Novo Nordisk Foundation . Support for this project was also provided by the European Foundation for the Study of Diabetes (EFSD) Albert Renold Travel Fellowship Programme (to MP), and from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 705869 (to AG).
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - 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.
AB - 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.
KW - C57BL/6JBomTac
KW - High-fat diet
KW - lysine malonylation
KW - NAD salvage pathways
KW - NAFLD
KW - SIRT5
UR - http://www.scopus.com/inward/record.url?scp=85044713087&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2018.01.025
DO - 10.1016/j.mce.2018.01.025
M3 - Journal article
C2 - 29408602
AN - SCOPUS:85044713087
SN - 0303-7207
VL - 473
SP - 245
EP - 256
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -