Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation

Hypoxia activates the hypoxia-inducible factor (HIF), promoting glycolysis and suppressing mitochondrial respiration. In the type 2 diabetic heart, glycolysis is suppressed whereas fatty acid metabolism is promoted. The diabetic heart experiences chronic hypoxia as a consequence of increased obstructive sleep apnoea and cardiovascular disease. Given the opposing metabolic effects of hypoxia and diabetes, we questioned whether diabetes affects cardiac metabolic adaptation to hypoxia. Control and type 2 diabetic rats were housed for 3 weeks in normoxia or 11% oxygen. Metabolism and function were measured in the isolated perfused heart using radiolabelled substrates. Following chronic hypoxia, both control and diabetic hearts upregulated glycolysis, lactate efflux and glycogen content and decreased fatty acid oxidation rates, with similar activation of HIF signalling pathways. However, hypoxia-induced changes were superimposed on diabetic hearts that were metabolically abnormal in normoxia, resulting in glycolytic rates 30% lower, and fatty acid oxidation 36% higher, in hypoxic diabetic hearts than hypoxic controls. Peroxisome proliferator-activated receptor α target proteins were suppressed by hypoxia, but activated by diabetes. Mitochondrial respiration in diabetic hearts was divergently activated following hypoxia compared with controls. These differences in metabolism were associated with decreased contractile recovery of the hypoxic diabetic heart following an acute hypoxic insult. In conclusion, type 2 diabetic hearts retain metabolic flexibility to adapt to hypoxia, with normal HIF signalling pathways. However, they are more dependent on oxidative metabolism following hypoxia due to abnormal normoxic metabolism, which was associated with a functional deficit in response to stress

Growth during the first summer at sea modulates sex-specific maturation schedule in Atlantic salmon

Recent decline in abundance of Atlantic salmon and concomitant changes in life history may result from a decline in the growth conditions during marine migration. Available literature suggests the existence of a sex-specific reaction norm linking maturation with environmental growth conditions at sea. However the extent to which this mechanism explains variations in age at maturity remains unclear. Using a historical collection of scales (1987-2017) from the Slune River, France, we showed that marine growth declined over the first summer, and remained stable during the subsequent periods at sea among returning salmon. Results support the hypothesis of a sex-specific probabilistic reaction norm, with individual probability to return after one year at sea increasing when growth increases. Females may require higher growth than males to attain their maturation threshold. This mechanism is a good candidate to explain temporal variability in sea-age at return at both the individual and population level in the Slune population and in many other southern European populations.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Toxicity of palytoxin, purified ovatoxin-a, ovatoxin-d and extracts of Ostreopsis cf. ovata on the Caco-2 intestinal barrier model

International audienceHuman intoxications in the Mediterranean Sea have been linked to blooms of the dinoflagellate Ostreopsis cf. ovata, producer of palytoxin (PlTX)-like toxins called ovatoxins (OVTXs). Exposure routes include only inhalation and contact, although PlTX-poisoning by seafood has been described in tropical regions. To address the impact of OVTXs on the intestinal barrier, dinoflagellate extracts, purified OVTX-a and -d and PlTX were tested on differentiated Caco-2 cells. Viability, inflammatory response and barrier integrity were recorded after 24h treatment. OVTX-a and -d were not cytotoxic up to 20ng/mL but increased IL-8 release, although to a lesser extent compared to PlTX. While PlTX and OVTX-a (at 0.5 and 5ng/mL respectively) affected intestinal barrier integrity OVTX-d up to 5ng/mL did not. Overall, OVTX-d was shown to be less toxic than OVTX-a and PlTX. Therefore, oral exposure to OVTX-a and -d could provoked lower acute toxicity than PlTX

A multi‐population approach supports common patterns in marine growth and maturation decision in Atlantic salmon ( Salmo salar L.) from southern Europe

Abstract This study provides a regional picture of long‐term changes in Atlantic salmon growth at the southern edge of their distribution, using a multi‐population approach spanning 49 years and five populations. We provide empirical evidence of salmon life history being influenced by a combination of common signals in the marine environment and population‐specific signals. We identified an abrupt decline in growth from 1976 and a more recent decline after 2005. As these declines have also been recorded in northern European populations, our study significantly expands a pattern of declining marine growth to include southern European populations, thereby revealing a large‐scale synchrony in marine growth patterns for almost five decades. Growth increments during their sea sojourn were characterized by distinct temporal dynamics. At a coarse temporal resolution, growth during the first winter at sea seemed to gradually improve over the study period. However, the analysis of finer seasonal growth patterns revealed ecological bottlenecks of salmon life histories at sea in time and space. Our study reinforces existing evidence of an impact of early marine growth on maturation decision, with small‐sized individuals at the end of the first summer at sea being more likely to delay maturation. However, each population was characterized by a specific probabilistic maturation reaction norm, and a local component of growth at sea in which some populations have better growth in some years might further amplify differences in maturation rate. Differences between populations were smaller than those between sexes, suggesting that the sex‐specific growth threshold for maturation is a well‐conserved evolutionary phenomenon in salmon. Finally, our results illustrate that although most of the gain in length occurs during the first summer at sea, the temporal variability in body length at return is buffered against the decrease in post‐smolt growth conditions. The intricate combination of growth over successive seasons, and its interplay with the maturation decision, could be regulating body length by maintaining diversity in early growth trajectories, life histories, and the composition of salmon populations

Effets de l'exposition aux nanoparticules d'or par inhalation sur la fonction placentaire et le phénotype de la descendance

International audienceAvec pour thématique "Ma mère, mon Placenta et Moi", ce colloque a pour objectif d’encourager la recherche sur le placenta et les pathologies obstétricales associées, de faciliter les collaborations internationales francophones, et les échanges scientifiques et méthodologique dans notre domaine

Effects of maternal Au-NP exposure by inhalation on feto-placental development and placental function, in a rabbit model

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Effects of maternal au-np exposure by inhalation on foeto-placental development and placental function, in a rabbit model

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