| First Author | Dall M | Year | 2018 |
| Journal | Mol Cell Endocrinol | Volume | 473 |
| Pages | 245-256 | PubMed ID | 29408602 |
| Mgi Jnum | J:266121 | Mgi Id | MGI:6207906 |
| Doi | 10.1016/j.mce.2018.01.025 | Citation | Dall M, et al. (2018) Hepatic NAD(+) levels and NAMPT abundance are unaffected during prolonged high-fat diet consumption in C57BL/6JBomTac mice. Mol Cell Endocrinol 473:245-256 |
| abstractText | 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. |
