Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2023 Feb 13;2(2):174–191. doi: 10.1038/s44161-023-00214-0

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Fig. 3 — a, Reporter metabolite analysis using differentially expressed genes in ventricles of Kdm8^fl/fl control and Kdm8^fl/fl;Myh6-Cre mutant mice at 2 and 6 months of age. The left panel illustrates all 46 reporter metabolites detected in 2-month-old hearts. The right panel illustrates the top 55 out of 718 reporter metabolites. Upregulated metabolites are in red, and downregulated metabolites are in blue. Data were analyzed by piano using distinct-directional P values. n = 2 mice per group at 2 months, and 3 mice per group at 6 months. b, Metabolomic networks from liquid chromatography–mass spectrometry (LC–MS) analysis of ventricles of control and mutant hearts at 2 and 6 months of age. Significantly altered metabolites are circled in black. Upregulated metabolites are in red, and downregulated metabolites are in blue. Each time point was independently analyzed by two-tailed Student’s t-test. P values were adjusted for false discovery by the Benjamini–Hochberg method. n = 5 controls and 7 mutants at 2 months; n = 9 controls and 5 mutants at 6 months. c, Quantification of NAM, NAD⁺ and 1-methyl-NAM by LC–MS, and ATP by fluorometric assay. Data are mean ± s.d. Each time point was analyzed by an independent two-tailed Student’s t-test, and two-way ANOVA with genotype, time point, and genotype–time point interaction as main effects. P values were adjusted for FDR by the Benjamini–Hochberg method. n = 5 controls and 7 mutants at 2 months; n = 9 controls and 5 mutants at 6 months for LC–MS. n = 3 hearts per group for ATP fluorometric assay. d, Heatmap of qPCR of genes encoding enzymes in the NAD⁺ pathway in 2-month-old ventricles. n = 4 hearts per group for the top 15 genes. n = 5 for Nmrk1 and Nmrk2. Significantly downregulated genes are in purple, and significantly upregulated genes are in yellow. e, Western blot of Nampt in 6-month-old ventricles. n = 5 hearts per group. The experiment was repeated twice with similar results. f, NAD⁺ biosynthetic pathways highlighting significantly downregulated and upregulated genes in Kdm8 mutant hearts. NAM, nicotinamide; NMN, nicotinamide mononucleotide; NR, nicotinamide riboside; MeNAM, methylnicotinamide; NAD⁺, nicotinamide adenine dinucleotide; Me4PY, N-methyl-4-pyridone-5-carboxamide.

Source data