Data from individual animals were plotted to study the correlations between NAD, lipid metabolism and hepatocyte proliferation.
(A) Positive correlation between NAD concentration and hepatocyte proliferation.
(B) Inverse correlation between hepatocyte proliferation and triglyceride content.
(C) Liver ATP content assessed pre or post hepatectomy in NR treated mice (n=6/group).
(D,E) ATP correlates positively with NAD concentration and hepatocyte proliferation.
(F) Proposed model: Hepatic NAD promotes fatty acid oxidation, thereby generating ATP necessary for hepatocellular growth and regeneration. NAD is directly required in the 3-hydroxyacyl-CoA dehydrogenase (HADH)-catalyzed step of fatty acid oxidation as well as the tricarboxylic acid cycle (TCA), but may also act indirectly via signaling enzymes such as Sirt1, which use NAD as a cosubstrate. NAD concentration can be modulated based on the expression of Nampt, which catalyzes the formation of nicotinamide mononucleotide (NMN) from nicotinamide and phosphoribosylpyrophosphate. Alternatively, NMN can be generated from NR by the action of NR kinase.
Error bars represent S.E.M. *, p < 0.05; **, p < 0.01.