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

Acknowledgements The authors wish to thank A. Hranitzky for support in bird mainte-nance, numerous students for their help in data collection, and N. Metcalfe, S. Dobson as well as S. Reichert for helpful comments on a previous draft. Funding AS was funded by a Marie Sklodowska-Curie Postdoctoral Fellowship (#658085) and a TCSM fellowship at the time of analyzing the results and writing the manuscriptPeer reviewedPostprin

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

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

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost

At the crossroad of metabolism and ageing (mitochondrial proximal control of oxidants and ultimate modulation of life history trade-offs)

L attention scientifique s est récemment portée sur l identification des mécanismes proximaux sous-tendant les compromis évolutifs;tels que les compromis existant entre croissance/reproduction et longévité. La production d espèces réactives de l oxygène (ROS )a été suggérée comme un candidat potentiel ,de par sa liaison étroite au métabolisme énergétique (sous- produits du fonctionnement mitochondrial) et son caractère inévitable. Si la production de ROS excède le niveau des défenses antioxydantes, une situation de stress oxydant va en résulter et a été associé au vieillissement . Puisque la mitochondrie n est pas uniquement la centrale énergétique de la cellule mais aussi le principal producteur de ROS, cette thèse s est attachée à clarifier les relations entre métabolisme énergétique , fonctionnement mitochondrial et stress oxydant ; avec des études concernant l impact d activités coûteuses en énergie (croissance, reproduction, thermogénèse) sur l équilibre de la balance oxydative.In recent years, scientific attention has turned towards the identification of the mechanisms underlying the trade- offs occurring between growth rate/reproductive investment and longevity. Amongst these mechanisms, the production of reactive oxygen species (ROS) appears to be a key factor due both to its universal and inevitable nature. ROS are by- products of energy processing by the mitochondria. If ROS production exceeds the capacity of the various antioxidant systems, oxidative stress will occur, and the accumulation of oxidative damage over time is thought to be a potential cause of ageing. Since mitochondria are not only the powerhouse of animal cells but also the main producer of ROS, this PhD thesis aimed to clarify the relationships between mitochondrial uncoupling state (i.e. efficiency to produce ATP), energy metabolism and oxidative stress. I investigated the impact of energy- demanding activities such as thermogenesis, reproduction and growth on oxidative homeostasis.STRASBOURG-Bib.electronique 063 (674829902) / SudocSudocFranceF

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

International audience2,4-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

Elevated corticosterone levels and severe weather conditions decrease parental investment of incubating Adélie penguins

International audienceCorticosterone, the main stress hormone in birds, mediates resource allocation, allowing animals to adjust their physiology and behaviour to changes in the environment. Incubation is a time and energy-consuming phase of the avian reproductive cycle. It may be terminated prematurely, when the parents' energy stores are depleted or when environmental conditions are severe. In this study, the effects of experimentally elevated baseline corticosterone levels on the parental investment of incubating male Adélie penguins were investigated. Incubation duration and reproductive success of 60 penguins were recorded. The clutches of some birds were replaced by dummy eggs, which recorded egg temperatures and rotation rates, enabling a detailed investigation of incubation behaviour. Corticosterone levels of treated birds were 2.4-fold higher than those of controls 18 days post treatment. Exogenous corticosterone triggered nest desertion in 61% of the treated birds; consequently reducing reproductive success, indicating that corticosterone can reduce or disrupt parental investment. Regarding egg temperatures, hypothermic events became more frequent and more pronounced in treated birds, before these birds eventually abandoned their nest. The treatment also significantly decreased incubation temperatures by 1.3 °C and lengthened the incubation period by 2.1 days. However, number of chicks at hatching was similar among successful nests, regardless of treatment. Weather conditions appeared to be particularly important in determining the extent to which corticosterone levels affected the behaviour of penguins, as treated penguins were more sensitive to severe weather conditions. This underlines the importance of considering the interactions of organisms with their environment in studies of animal behaviour and ecophysiology

Telomere length correlations among somatic tissues in adult zebra finches.

Telomeres are repetitive non coding DNA sequences located at the end of eukaryotic chromosomes, which maintain the integrity of the genome by hiding the chromosome ends from being recognised as double stranded breaks. Telomeres are emerging as biomarkers for ageing and survival, and are susceptible to reflect different individual life history trajectories. In particular, the telomere length with which one starts in life has been shown to be linked with individual life-long survival, suggesting that telomere dynamics can be a proxy for individual fitness and thereby be implicated in evolutionary trade-offs. As a consequence, an increasing number of studies were conducted on telomeres in the fields of ecology and evolutionary biology, in which telomere length was almost exclusively measured from blood samples. However, not only do the number of repeats of the telomeric sequences vary among species, but also within species with great inter-individual telomere lengths variability with age, tissues, and chromosomes. This raises the issue of the exact biological meaning of telomere measurement in blood cells and stimulated the study of the correlation of telomere lengths among tissues over age. By measuring telomere length in adult zebra finches (Taeniopygia guttata) in different somatic tissues displaying variable cell turnovers (bone marrow, brain, spleen, pectoral muscle, heart, liver and in red blood cells), we checked that the measure of telomere length in red blood cells is related to telomere lengths in the other tissues. Here we show significant relationships between the telomere lengths of red blood cells and several somatic tissues at adulthood. As red blood cells are easily accessible and suitable for the longitudinal monitoring of the individual rate of telomere loss, our study confirms that telomere length measured in red blood cells could serve as a surrogate for telomere length in the whole avian organism

(Table 1) Breeding parameters for 60 male Adélie penguins (Pygoscelis adeliae) at station Dumont d'Urville (Antarctica) depending on treatment (control vs. CORT)

Corticosterone, the main stress hormone in birds, mediates resource allocation, allowing animals to adjust their physiology and behaviour to changes in the environment. Incubation is a time and energy-consuming phase of the avian reproductive cycle. It may be terminated prematurely, when the parents' energy stores are depleted or when environmental conditions are severe. In this study, the effects of experimentally elevated baseline corticosterone levels on the parental investment of incubating male Adelie penguins were investigated. Incubation duration and reproductive success of 60 penguins were recorded. The clutches of some birds were replaced by dummy eggs, which recorded egg temperatures and rotation rates, enabling a detailed investigation of incubation behaviour. Corticosterone levels of treated birds were 2.4-fold higher than those of controls 18 days post treatment. Exogenous corticosterone triggered nest desertion in 61% of the treated birds; consequently reducing reproductive success, indicating that corticosterone can reduce or disrupt parental investment. Regarding egg temperatures, hypothermic events became more frequent and more pronounced in treated birds, before these birds eventually abandoned their nest. The treatment also significantly decreased incubation temperatures by 1.3 °C and lengthened the incubation period by 2.1 days. However, the number of chicks at hatching was similar among successful nests, regardless of treatment. Weather conditions appeared to be particularly important in determining the extent to which corticosterone levels affected the behaviour of penguins, as treated penguins were more sensitive to severe weather conditions. This underlines the importance of considering the interactions of organisms with their environment in studies of animal behaviour and ecophysiology