ArticleJCI insight2017
Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Alterations in biopterin metabolism and the effects of tetrahydrobiopterin supplementation in a rat model of short bowel syndrome.Pediatric surgery international · 2026Article
- Cardiomyocyte tetrahydrobiopterin synthesis regulates fatty acid metabolism and susceptibility to ischaemia-reperfusion injury.Experimental physiology · 2023Article
- Interaction between Butyrate and Tumor Necrosis Factor α in Primary Rat Colonocytes.Biomolecules · 2023Article
- Transplantation of fat tissues and iPSC-derived energy expenditure adipocytes to counteract obesity-driven metabolic disorders: Current strategies and future perspectives.Reviews in endocrine & metabolic disorders · 2022Review
- An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications.Frontiers in endocrinology · 2022Review
- Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?Frontiers in cell and developmental biology · 2021Review
- Role of the Transient Receptor Potential Vanilloid Type 1 (TRPV1) in the Regulation of Nitric Oxide Release in Wistar Rat Aorta.Oxidative medicine and cellular longevity · 2021Article
- Tetrahydrobiopterin Improves Recognition Memory in the Triple-Transgenic Mouse Model of Alzheimer's Disease, Without Altering Amyloid-β and Tau Pathologies.Journal of Alzheimer's disease : JAD · 2021Article
- The role of adipose tissue in cardiovascular health and disease.Nature reviews. Cardiology · 2019 · on this mapReview
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brown adipose tissue (BAT) is a central organ that acts to increase energy expenditure; its regulatory factors could be clinically useful in the treatment of obesity. Tetrahydrobiopterin (BH4) is an essential cofactor of tyrosine hydroxylase and nitric oxide synthase (NOS). Although BH4 regulates the known regulatory factors of BAT, such as noradrenaline (NA) and NO, participation of BH4 in BAT function remains unclear. In the present study, we investigate the role of BH4 in the regulation of BAT. Hph-1 mice, a mouse model of BH4 deficiency, exhibit obesity, adiposity, glucose intolerance, insulin resistance, and impaired BAT function. Impaired BAT function was ameliorated together with systemic metabolic disturbances by BAT transplantation from BH4-sufficient mice (control mice) into BH4-deficient mice, strongly suggesting that BH4-induced BAT has a critical role in the regulation of systemic energy metabolism. Both NA derived from the sympathetic nerve and NO derived from endothelial NOS in the blood vessels participate in the regulation of BH4. In addition, a direct effect of BH4 in the stimulation of brown adipocytes via NO is implicated. Taken together, BH4 activates BAT and regulates systemic energy metabolism; this suggests an approach for metabolic disorders, such as obesity and diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.