Up-regulation of avian uncoupling protein in cold-acclimated and hyperthyroid ducklings prevents reactive oxygen species production by skeletal muscle mitochondria

<p>Abstract</p> <p>Background</p> <p>Although identified in several bird species, the biological role of the avian homolog of mammalian uncoupling proteins (avUCP) remains extensively debated. In the present study, the functional properties of isolated mitochondria were examined in physiological or pharmacological situations that induce large changes in avUCP expression in duckling skeletal muscle.</p> <p>Results</p> <p>The abundance of avUCP mRNA, as detected by RT-PCR in gastrocnemius muscle but not in the liver, was markedly increased by cold acclimation (CA) or pharmacological hyperthyroidism but was down-regulated by hypothyroidism. Activators of UCPs, such as superoxide with low doses of fatty acids, stimulated a GDP-sensitive proton conductance across the inner membrane of muscle mitochondria from CA or hyperthyroid ducklings. The stimulation was much weaker in controls and not observed in hypothyroid ducklings or in any liver mitochondrial preparations. The production of endogenous mitochondrial reactive oxygen species (ROS) was much lower in muscle mitochondria from CA and hyperthyroid ducklings than in the control or hypothyroid groups. The addition of GDP markedly increased the mitochondrial ROS production of CA or hyperthyroid birds up to, or above, the level of control or hypothyroid ducklings. Differences in ROS production among groups could not be attributed to changes in antioxidant enzyme activities (superoxide dismutase or glutathione peroxidase).</p> <p>Conclusion</p> <p>This work provides the first functional <it>in vitro </it>evidence that avian UCP regulates mitochondrial ROS production in situations of enhanced metabolic activity.</p

Long term highly saturated fat diet does not induce NASH in Wistar rats

BACKGROUND: Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. METHODS: 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. RESULTS: MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard). CONCLUSION: Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH

How to measure mitochondrial function in birds using red blood cells : a case study in the king penguin and perspectives in ecology and evolution

We are grateful to the French Polar Institut (IPEV) for providing logistical support for this study through the programs 119 & 131, A. Bourguignon, Y. Handrich and A. Lewden for their contribution to the muscle biopsy sampling, V. Viblanc for his support through the IPEV program 119, and three anonymous reviewers for their help in improving the manuscript. A. Stier was supported by a Marie Sklodowska- Curie Postdoctoral Fellowship (#658085). Authors declare no conflict of interest.Peer reviewedPostprin

Stéatohépatite et adaptations métaboliques:<br />Effets d'un régime enrichi en lipides saturés, ou carencé en choline et méthionine, sur la bioénergétique et le métabolisme hépatique de rat

Non alcoholic steatohepatitis (NASH) is a raising pathology in northern countries, due to obesity and insulin-resistance. To date, NASH pathogenesis is poorly understood because suitable animal models are missing and an appropriate treatment to prevent patient NASH evolution in cirrhosis is still lacking. The aim of this work was to study the bioenergetic and metabolic modifications in hepatocyte and liver mitochondria isolated from NASH suffering rats. In a first part, we elaborated a diet with saturated fatty acids to induce a NASH. After 14 weeks of both diets, no steatosis could be observed in the rat livers. Studies carried out on isolated hepatocytes and liver mitochondria showed no modification in the liver bioenergetic or metabolism characteristics in comparison to control rats. By contrast, a modification in tissue repartition was observed, with a mass increase in white and brown adipose tissues. In this study, the absence of liver steatosis might be due to a huge increase in white adipose tissue storage and thermogenic lipid oxidation in the brown adipose tissue, to “burn” the caloric excess. The second part of this work was devoted to study bioenergetic and metabolic modifications induced by a choline and methionine deficient diet, known to induce NASH in rats. Liver mitochondria and hepatocytes isolated from treated rats presented an increase in the respiration rate. This higher oxygen consumption was due to an uncoupling of the respiratory chain by a “proton leak” and a “redox slipping” at the cytochrome c oxidase level. This uncoupling yielded in higher lipid oxidation and lower reactive oxygen species production. Moreover, studies with isolated hepatocytes showed an increased lipid oxidation and neoglucogenesis.These results suggest mitochondrial and metabolic adaptations of NASH rat liver which permit to limit a lipid overload and an oxidative stressLa stéatohépatite non alcoolique (NASH) est une pathologie émergente dans nos pays industrialisés du fait de l'obésité et de l'insulino-résistance. A ce jour, la pathogenèse de la NASH est mal connue et il n'existe pas de traitement prévenant son évolution cirrhogène chez certains patients. Le but de ce travail consistait à étudier les modifications bioénergétiques et métaboliques de mitochondries hépatiques et d'hépatocytes isolés de rats atteints de NASH. Dans un premier temps, nous avons élaboré un régime alimentaire enrichi en acides gras saturés afin d'induire une NASH. Au terme de 14 semaines de régime, nous n'avons pas mis en évidence de surcharge lipidique au niveau du foie des animaux recevant ce régime enrichi. Les mesures effectuées avec des mitochondries isolées de foies et avec des hépatocytes isolés n'ont montré aucune différence au niveau de la bioénergétique ou du métabolisme hépatique entre les différents groupes de rats. En revanche, une modification de la répartition tissulaire a été observée, avec une augmentation des masses des tissus adipeux blanc et brun. Dans cette étude, l'absence de stéatose hépatique et de NASH semble due à une augmentation du stockage des lipides au niveau du tissu adipeux blanc, et à une augmentation de leur oxydation par un processus thermogène au niveau du tissu adipeux brun, permettant ainsi de « brûler » l'excès calorique.La deuxième partie du travail concernait l'étude des modifications bioénergétiques et métaboliques induites par un régime carencé en choline et méthionine connu pour induire une NASH chez le rat. Nous avons montré que les mitochondries de foie et les hépatocytes isolés de rats traités, avaient une respiration augmentée. Cette stimulation de la respiration était due à un découplage de la chaîne respiratoire par un mécanisme de « proton leak » ET de « redox slipping » au niveau de la cytochrome c oxydase. Ce découplage avait pour conséquence de stimuler l'utilisation de substrats lipidiques et de diminuer la production de radicaux libres de l'oxygène. En parallèle, l'étude avec des hépatocytes isolés nous montre une augmentation de l'oxydation lipidique et de la néoglucogenèse. Ces résultats suggèrent des adaptations des fonctions mitochondriales et métaboliques des foies de rats atteints de NASH qui permettraient de limiter la surcharge lipidique et le stress oxydan

3D models related to the publication: Wild versus lab house mice: Effects of age, diet, and genetics on molar geometry and topography.

International audienceThis contribution contains 3D models of upper molar rows of house mice (Mus musculus domesticus). The erupted parts of the right row and of the first upper molar are presented for specimens belonging to four groups: wild-trapped mice, wild-derived lab offspring, a typical laboratory strain (Swiss) and hybrids between wild-derived and Swiss mice. These models are analyzed in the following publication: Savriama et al 2021: Wild versus lab house mice: Effects of age, diet, and genetics on molar geometry and topography

Fasting enhances mitochondrial efficiency in duckling skeletal muscle by acting on the substrate oxidation system

International audienceDuring food deprivation, animals must develop physiological responses to maximize energy conservation and survival. At the subcellular level, energy conservation is mainly achieved by a reduction in mitochondrial activity and an upregulation of oxidative phosphorylation efficiency. The aim of this study was to decipher mechanisms underlying the increased mitochondrial coupling efficiency reported in fasted birds. Mitochondrial oxidative phosphorylation activity, efficiency and membrane potential were measured in mitochondria isolated from the gastrocnemius muscle of ducklings. The content and activities of respiratory chain complexes were also determined. Results from ducklings fasted for 6 days were compared with ducklings fed ad libitum. Here, we report that 6 days of fasting improved coupling efficiency in muscle mitochondria of ducklings by depressing proton-motive force through the downregulation of substrate oxidation reactions. Fasting did not change the basal proton conductance of mitochondria but largely decreased the oxidative phosphorylation activity, which was associated with decreased activities of succinate–cytochrome c reductase (complexes II–III) and citrate synthase, and altered contents in cytochromes b and c+c1. In contrast, fasting did not change cytochrome aa3 content or the activity of complexes I, II and IV. Altogether, these data show that the lower capacity of the respiratory machinery to pump protons in ducklings fasted for 6 days generates a lower membrane potential, which triggers a decreased proton leak activity and thus a higher coupling efficiency. We propose that the main site of action would be located at the level of co-enzyme Q pool/complex III of the electron transport chain

Data from: Allometry of mitochondrial efficiency is set by metabolic intensity

Metabolic activity sets the rates of individual resource uptake from the environment and resource allocations. For this reason, relationship with body size has been heavily documented from ecosystems to cells. Until now, most of the studies used the fluxes of oxygen as proxy of energy output without knowledge of the efficiency of biological systems to convert oxygen into ATP. The aim of this study was to examine the allometry of coupling efficiency (ATP/O) of skeletal muscle mitochondria isolated from twelve mammal species ranging from 6 g to 550 kg. Mitochondrial efficiencies were measured at different steady states of phosphorylation. The efficiencies increased sharply at higher metabolic rates. We have shown that body mass dependence of mitochondrial efficiency depends on metabolic intensity in skeletal muscles of mammals. Mitochondrial efficiency positively depends on body mass when mitochondria are close to the basal metabolic rate, however the efficiency is independent of body mass at the maximum metabolic rate. As a result, it follows that large mammals exhibit a faster dynamic increase in ATP/O than small species when mitochondria shift from basal to maximal activities. Finally, the invariant value of maximal coupling efficiency across mammal species could partly explain why scaling exponent values are very close to 1 at maximal metabolic rates

Mean data set (Boel et al 2019)

Mean values of mitochondrial bioenergetics parameters for all of the species shown in the manuscript

Comparative genomic analysis identifies small open reading frames (sORFs) with peptide-encoding features in avian 16S rDNA

International audienc

3D models related to the publication: Molar wear in house mice: insight into diet preferences at an ecological time scale?

This contribution contains 3D models of upper molar rows of house mice (Mus musculus domesticus) belonging to Western European commensal and Sub-Antarctic feral populations. These two groups are characterized by different patterns of wear and alignment of the three molars along the row, related to contrasted masticatory demand in relation with their diet. These models are analyzed in the following publication: Renaud et al 2023, "Molar wear in house mice, insight into diet preferences at an ecological time scale?", https://doi.org/10.1093/biolinnean/blad091