The Metabolic Consequences of Hepatic AMP-Kinase Phosphorylation in Rainbow Trout

AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, is proposed to function as a “fuel gauge” to monitor cellular energy status in response to nutritional environmental variations. However, in fish, few studies have addressed the metabolic consequences related to the activation of this kinase. This study demonstrates that the rainbow trout (Oncorhynchus mykiss) possesses paralogs of the three known AMPK subunits that co-diversified, that the AMPK protein is present in the liver and in isolated hepatocytes, and it does change in response to physiological (fasting-re-feeding cycle) and pharmacological (AICAR and metformin administration and incubations) manipulations. Moreover, the phosphorylation of AMPK results in the phosphorylation of acetyl-CoA carboxylase, a main downstream target of AMPK in mammals. Other findings include changes in hepatic glycogen levels and several molecular actors involved in hepatic glucose and lipid metabolism, including mRNA transcript levels for glucokinase, glucose-6-phosphatase and fatty acid synthase both in vivo and in vitro. The fact that most results presented in this study are consistent with the recognized role of AMPK as a master regulator of energy homeostasis in living organisms supports the idea that these functions are conserved in this piscine model

Acides aminés à chaîne ramifiée et insulino-sensibilité : amis ou ennemis ?

Article ayant fait l’objet d’une conférence lors des journées francophones de nutrition de 2017Branched-chain amino acids (BCAA) are essential amino acids, and play a key role in the regulation of energy homeostasis and nutritional metabolism. However, BCAA are not only substrates for protein synthesis, as they also serve as signalling molecules regulating the metabolism of glucose, lipids and proteins, via the PI3 K/AKT/mTOR signalling pathways. Although it has been shown that BCAA can improve metabolic health, an increase in their plasma levels has also been associated with a high risk of future type 2 diabetes (T2D). One of the proposed explanations for this phenotype concerns the overactivation of mTORC1 by BCAA, as it has been shown that could induce insulin resistance. Alternatively, a model of dysmetabolism also proposes that the accumulation of BCAA-derived metabolites would favour the mitochondrial dysfunction of β cells and adipocytes expressed during T2D. This review will therefore focus on recent insights associated with metabolic and regulatory pathways of BCAA, and the mechanisms underlying the relationship between BCAA and the associated pathological processes.Les acides aminés à chaîne ramifiée (AACR) jouent un rôle primordial dans la régulation de l’homéostasie énergétique et du métabolisme nutritionnel. Mais les AACR ne sont pas seulement des substrats pour la synthèse protéique, car ils servent également de molécules de signalisation régulant le métabolisme du glucose, des lipides et des protéines, via les voies PI3 K/AKT/mTOR. Bien qu’il ait été montré que les AACR peuvent améliorer la santé métabolique, une augmentation de leur taux plasmatique a été également associée à un risque élevé de diabète de type 2 (DT2). L’une des explications proposées concerne la suractivation de mTORC1 par les AACR. Alternativement, un modèle de dysmétabolisme propose que l’accumulation des métabolites dérivés des AACR favoriserait le dysfonctionnement mitochondrial des cellules β et adipocytaires exprimées lors du DT2. Cette revue se concentre donc sur les découvertes récentes associées aux voies métaboliques et de régulation des AACR, et les mécanismes sous-jacents à la relation entre les AACR et les processus pathologiques associés

Evolution de la santé au cours du vieillissement : approches multi-omiques, intérêt des modèles pré-cliniques

Symposium CRNHCRNH AuvergneEvolution de la santé au cours du vieillissement : approches multi-omiques, intérêt des modèles pré-cliniques. JFN 2018, Journées Francophones de Nutritio

Acides aminés à chaîne ramifiée et insulino-sensibilité : amis ou ennemis ?

National audienc

Transition protéique et risque cardiométabolique : apport des omiques et projet en cours ProVegOmics

International audienc

Peut-on se servir de la métabolomique pour identifier les étapes précoces associées à l'installation des dérèglements métaboliques ?

Peut-on se servir de la métabolomique pour identifier les étapes précoces associées à l'installation des dérèglements métaboliques ? . Assises Jeunes Chercheurs Département Alim

Preclinical Modelling: How can swine model contribute ?

Preclinical Modelling: How can swine model contribute ?. Use of Animal Models for Pathophysiological and Nutrigenomic Researc

Metabolomics analysis across the liver of obese minipigs after a hyper-caloric diet

The first NuGO thematic webinar took place on June 25 2020 9:00-11:00 (CET). The webinar will discuss the relevance of metabolites, in particular those derived from untargeted metabolomics studies, at the boundaries between food, nutrition and metabolic diseases. Four speakers from NuGO institutions will present and discuss mechanistically their research data from animal models and human subjects. Each presentation will be concluded with a short round of questions by the audience

Involvement of lactate in glucose metabolism and glucosensing function in selected tissues of rainbow trout

SUMMARY The aim of this study was to obtain evidence in rainbow trout for a role of lactate in glucose homeostasis as well as in the function of glucosensing tissues. In a first set of experiments, trout were injected, either (1)intraperitoneally (N=8) with 5 ml kg–1 of Cortland saline alone (control) or saline containing l-(+)-lactate (22.5 mg kg–1 or 45 mg kg–1), oxamate (22.5 mg kg–1) or d-glucose (500 mg kg–1),or (2) intracerebroventricularly (N=11) with 1 μl 100 g–1 body mass of Cortland saline alone (control) or containing d-glucose (400 μg μl–1) or l-(+)-lactate (400 μg μl–1), with samples being obtained 6 h after treatment. In a second set of experiments,hypothalamus, hindbrain and Brockmann bodies were incubated in vitrofor 1 h at 15°C in modified Hanks' medium containing 2, 4 or 8 mmol l–1l-(+)-lactate alone (control) or with 50 mmol l–1 oxamate, 1 mmol l–1 DIDS, 1 mmol l–1 dichloroacetate, 10 mmol l–12-deoxy-d-glucose, 1 mmol l–1α-cyano-4-hydroxy cinnamate or 10 mmol l–1d-glucose. The response of parameters assessed (metabolite levels,enzyme activities and glucokinase expression) in tissues provided evidence for(1) a role for lactate in the regulation of glucose homeostasis through changes not only in brain regions but also in liver energy metabolism, which are further reflected in changes in plasma levels of metabolites; (2) the possible presence in trout brain of an astrocyte–neuron lactate shuttle similar to that found in mammals; and (3) the lack of capacity of lactate to mimic in vitro (but not in vivo) glucose effects in fish glucosensing regions