Long-term intake of the illegal diet pill DNP reduces lifespan in a captive bird model

Antoine Stier (1, 2) , Pierre Bize (3) , Sylvie Massemin (4) , François Criscuolo (4)

1 University of Turku
2 University of Glasgow
3 University of Aberdeen
4 DEPE-IPHC - Département Ecologie, Physiologie et Ethologie

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.

Mots clés: 2; 4--dinitrophenol; toxicity; mitochondrial uncoupling; oxidative stress; survival; longevity

Domaines: Sciences de l'environnement

Antoine Stier, Pierre Bize, Sylvie Massemin, François Criscuolo. Long-term intake of the illegal diet pill DNP reduces lifespan in a captive bird model. Comparative Biochemistry and Physiology - Part C: Comparative Pharmacology and Toxicology, 2021, ⟨10.1016/j.cbpc.2020.108944⟩. ⟨hal-03035300⟩