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Long-term intake of the illegal diet pill DNP reduces lifespan in a captive bird model
Antoine Stier1, Pierre Bize2, Sylvie Massemin3
1Department of Biology, University of Turku, Turku, Finland; Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK.
Abstract:
2,4-Dinitrophenol (DNP), a molecule uncoupling mitochondrial oxidative phosphorylation from oxygen consumption, is illegally used by humans as a diet pill, but is nonetheless investigated as a potential human medicine against 'metabesity'. Due to its proven acute toxicity and the scarceness of long-term studies on DNP administration in vertebrates, we determined the impact of a long-term DNP treatment (~4 mg.kg-1.day-1, i.e. within the range taken illegally by humans) on body mass, metabolism, ageing and lifespan in a captive bird model, the zebra finch. The chronic absorption of DNP over life (>4 years) led to a mild increase in energy expenditure (ca. +11% compared to control group), without significantly altering the normal slight increase in body mass with age. DNP did not significantly influence the alteration of physical performance, the rise in oxidative damage, or the progressive shortening of telomeres with age. However, DNP-treated individuals had a significantly shorter lifespan (ca. -21% in median lifespan compared to control group), thereby raising potential concerns about DNP use as a diet pill or medicine.
Insights
2,4-Dinitrophenol (DNP) increases energy expenditure but significantly shortens lifespan in a bird model. This study raises concerns about DNP
Area of Science:
- Biochemistry
- Gerontology
- Pharmacology
Background:
- 2,4-Dinitrophenol (DNP) is an uncoupler of mitochondrial oxidative phosphorylation.
- DNP is illegally used as a diet pill and investigated for 'metabesity'.
- Limited long-term vertebrate studies exist on DNP's toxicity and effects.
Purpose of the Study:
- To determine the long-term impact of DNP on body mass, metabolism, aging, and lifespan.
- To assess DNP's effects in a captive bird model (zebra finch).
- To evaluate DNP's safety for potential medicinal or dietary use.
Main Methods:
- Chronic administration of DNP (~4 mg.kg⁻¹.day⁻¹) to zebra finches over their lifespan (>4 years).
- Monitoring body mass, energy expenditure, physical performance, oxidative damage, and telomere length.
- Comparing DNP-treated individuals with a control group.
Main Results:
- Chronic DNP exposure resulted in a mild increase in energy expenditure (+11%).
- Body mass, physical performance, oxidative damage, and telomere shortening were not significantly altered by DNP.
- DNP treatment significantly reduced median lifespan by approximately 21%.
Conclusions:
- Long-term DNP administration shortens lifespan in zebra finches.
- DNP's uncoupling effect does not prevent age-related decline in other biomarkers.
- Concerns exist regarding the safety of DNP as a diet pill or potential medicine.
