{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:03:40Z","timestamp":1784610220611,"version":"3.55.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    One of the key regulatory mechanisms in adipose biology is the NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    -associated protein coding genes were extracted. Pathway enrichment analysis revealed multiple canonical pathways significantly associated with these genes, including\n                    <jats:italic>thermogenesis<\/jats:italic>\n                    , the\n                    <jats:italic>PPAR signaling pathway<\/jats:italic>\n                    , the\n                    <jats:italic>AMPK signaling pathway<\/jats:italic>\n                    , and\n                    <jats:italic>adipogenesis<\/jats:italic>\n                    . In addition, several cellular pathways were identified for which direct experimental evidence of NAD\n                    <jats:sup>+<\/jats:sup>\n                    involvement is currently lacking, such as the\n                    <jats:italic>apelin signaling pathway<\/jats:italic>\n                    and the\n                    <jats:italic>relaxin signaling pathway<\/jats:italic>\n                    . Protein-protein interaction analysis revealed three distinct protein clusters related to\n                    <jats:italic>positive regulation of cold-induced thermogenesis<\/jats:italic>\n                    ,\n                    <jats:italic>inflammation<\/jats:italic>\n                    , and\n                    <jats:italic>cellular respiration<\/jats:italic>\n                    . Master regulator analysis identified several well-established regulators, such as leptin, PRDM16, PPARGC1A, AMP, glucose, fructose, and rosiglitazone, as well as regulators that have not yet been directly investigated in the context of NAD\n                    <jats:sup>+<\/jats:sup>\n                    function in adipose biology. Finally, analysis of disease associations of NAD\n                    <jats:sup>+<\/jats:sup>\n                    -associated protein coding genes revealed links to nutritional and cardiometabolic diseases. In conclusion, this study highlights both well-established and previously unexplored canonical pathways and regulators of biological processes associated with the role of NAD\n                    <jats:sup>+<\/jats:sup>\n                    in adipose biology, thereby identifying potential targets for future experimental investigation. Additionally, our systematic literature search revealed a notable lack of studies employing global transcriptomic approaches, as well as multi-omics studies with coupled bioinformatic analyses, which are essential for obtaining an in-depth and comprehensive understanding of the role of NAD\n                    <jats:sup>+<\/jats:sup>\n                    in adipose biology.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1807667","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:19:06Z","timestamp":1784607546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative functional bioinformatic analysis of NAD+-associated protein coding genes in adipose tissue (dys)function \u2013 evidence from targeted rodent transcriptomic studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Filip","family":"Postolov","sequence":"first","affiliation":[{"name":"Faculty of Medical Sciences, Goce Delcev University","place":["Stip, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragan","family":"Milenkovic","sequence":"additional","affiliation":[{"name":"Plants for Human Health Institute, Department of Food Bioprocessing & Nutrition Sciences, North Carolina State University","place":["Kannapolis, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Ruskovska","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Goce Delcev University","place":["Stip, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.5114\/aoms.2013.33181","article-title":"Biochemistry of adipose tissue: an endocrine organ","volume":"9","author":"Coelho","year":"2013","journal-title":"Arch Med Sci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.115.306885","article-title":"Obesity-induced changes in adipose tissue microenvironment and their impact on cardiovascular disease","volume":"118","author":"Fuster","year":"2016","journal-title":"Circ Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.04.002","article-title":"Oxidative stress and protein carbonylation in adipose tissue - implications for insulin resistance and diabetes mellitus","volume":"92","author":"Ruskovska","year":"2013","journal-title":"J Proteomics"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/lifemedi\/lnaf028","article-title":"Fat talks first: how adipose tissue sets the pace of aging","volume":"4","author":"Liu","year":"2025","journal-title":"Life Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.3390\/biomedicines11051290","article-title":"The role of adipokines in health and disease","volume":"11","author":"Clemente-Su\u00e1rez","year":"2023","journal-title":"Biomedicines"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2020-00147","article-title":"Adipocyte-derived extracellular vesicles in health and diseases: nano-packages with vast biological properties","volume":"3","author":"Le Lay","year":"2021","journal-title":"FASEB Bioadv"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2023.102046","article-title":"Recent developments in adipose tissue-secreted factors and their target organs","volume":"80","author":"Navarro-Perez","year":"2023","journal-title":"Curr Opin Genet Dev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-031620-095446","article-title":"Cellular heterogeneity in adipose tissues","volume":"83","author":"Corvera","year":"2021","journal-title":"Annu Rev Physiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s11154-023-09850-0","article-title":"An update on the secretory functions of brown, white, and beige adipose tissue: towards therapeutic applications","volume":"25","author":"Ghesmati","year":"2024","journal-title":"Rev Endocr Metab Disord"},{"key":"B10","doi-asserted-by":"publisher","first-page":"595","DOI":"10.4093\/dmj.2023.0011","article-title":"Adipose tissue and metabolic health","volume":"47","author":"An","year":"2023","journal-title":"Diabetes Metab J"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4159\/harvard.9780674366701.c132","article-title":"The alcoholic ferment of yeast-juice. 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