Integrative functional bioinformatic analysis of NAD+-associated protein coding genes in adipose tissue (dys)function - evidence from targeted rodent transcriptomic studies
Abstract
One of the key regulatory mechanisms in adipose biology is the NAD+/SIRT axis, which is disrupted in conditions such as obesity and insulin resistance. In recent years, increasing attention has been directed toward understanding the role of NAD+ in adipose biology, including through gene expression analyses. However, most published studies have focused on a limited set of preselected genes, and an integrated analysis of genes associated with NAD+ alterations in adipose tissue is lacking. The aim of this study was to conduct a systematic literature search to identify rodent studies reporting significant modulation of NAD+ levels in adipose tissue, along with significant changes in gene expression within the same adipose depot. The extracted genes were then subjected to integrative functional bioinformatic analyses to identify significantly enriched canonical pathways, protein-protein interactions, master regulators, and associations with human diseases. We identified 17 studies, from which 113 unique NAD+-associated protein coding genes were extracted. Pathway enrichment analysis revealed multiple canonical pathways significantly associated with these genes, including thermogenesis, the PPAR signaling pathway, the AMPK signaling pathway, and adipogenesis. In addition, several cellular pathways were identified for which direct experimental evidence of NAD+ involvement is currently lacking, such as the apelin signaling pathway and the relaxin signaling pathway. Protein-protein…
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