{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:13:34Z","timestamp":1783509214908,"version":"3.55.0"},"reference-count":50,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>Glucocorticoid excess induces a plethora of metabolic disturbances, including obesity, muscle atrophy, hepatic steatosis and increased energy expenditure, which are hallmark features of Cushing\u2019s syndrome. Despite the understanding of these outcomes, it remains unclear how glucocorticoid excess affects the metabolically critical nicotinamide adenine dinucleotide (NAD+) and related metabolites and transcripts, including redox cofactors, intermediates and biosynthetic enzymes. Furthermore, the therapeutic potential of NAD+ precursor supplementation in this context is unknown. Here, we investigated tissue- and sex-specific effects of sustained corticosterone treatment on NAD+ and its related metabolites and transcripts in skeletal muscle and liver of male and female mice and assessed the efficacy of nicotinamide riboside (NR) supplementation in preventing glucocorticoid-induced metabolic dysfunction. Using LC\u2013MS and gene expression analyses, we demonstrate that glucocorticoid excess increases NAD+ and NAAD levels in skeletal muscle, alongside modest changes in salvage pathway gene expression in males and females. However, NADP+ was increased in males only. In the liver, glucocorticoid treatment decreased NADPH and increased the NADP+\/NADPH ratio in males and females, with widespread downregulation of biosynthetic enzymes despite stable NAD+ levels. NR supplementation failed to prevent classical features of glucocorticoid excess, including increased body weight, muscle atrophy, adiposity, hepatic triglyceride accumulation and elevated energy expenditure. These findings not only reveal novel effects of glucocorticoid excess on NAD+ and related metabolites and transcripts but also question the importance of NAD+ in glucocorticoid-induced metabolic dysfunction. Consequently, whilst NAD+ pathways are impacted by glucocorticoid excess, our data show no therapeutic benefit of NR supplementation under the conditions tested and do not support its efficacy in this model of glucocorticoid excess.<\/jats:p>","DOI":"10.1530\/joe-26-0011","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:54:05Z","timestamp":1778522045000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":0,"title":["Glucocorticoid excess disrupts NAD+ homeostasis in male and female mice"],"prefix":"10.1530","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1749-9229","authenticated-orcid":true,"given":"Samuel 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