ArticleThe Journal of biological chemistry2016
The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Gut-brain axis in health and brain disease.Chinese medical journal · 2026Review
- From sympathetic storm to systemic inflammation: spatiotemporal dynamics of the brain-lung axis in neurogenic pulmonary edema.Frontiers in neuroscience · 2026Review
- Scopoletin mitigates maternal separation-induced anxiety-like and depression-like behaviors in male mice through modulation of the Sirt1/NF-κB pathway.Psychopharmacology · 2024Article
- SIRT1 and ZNF350 as novel biomarkers for osteoporosis: a bioinformatics analysis and experimental validation.Molecular biology reports · 2024Article
- Emphasizing the Crosstalk Between Inflammatory and Neural Signaling in Post-traumatic Stress Disorder (PTSD).Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Novel Role of the SIRT1 in Endocrine and Metabolic Diseases.International journal of biological sciences · 2023Review
- A neuronal action of sirtuin 1 suppresses bone mass in young and aging mice.The Journal of clinical investigation · 2022Article
- Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis.Aging cell · 2021Review
- Interplay between oxidative stress, SIRT1, reproductive and metabolic functions.Current research in physiology · 2021Review
- The Versatility of Sirtuin-1 in Endocrinology and Immunology.Frontiers in cell and developmental biology · 2020Review
- The Essential Role of SIRT1 in Hypothalamic-Pituitary Axis.Frontiers in endocrinology · 2018Review
- SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis.PloS one · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamic-pituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH.
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