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INRA
24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

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Human Nutrition Unit

Zone de texte éditable et éditée et rééditée

To understand

     

To characterize the molecular mechanisms of regulation of amino acid/protein homeostasis



    To understand the mechanisms of disease-associated anorexia
We study the role of eIF2a/ATF4 signaling in anorexia associated with catabolic states.
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Figure Anorexie
Context

Many pathological conditions (cancers, sepsis...) are associated with cachexia resulting from increased catabolism and loss of appetite. Anorexia associated with pathology (secondary anorexia) is observed in nearly half of cancer patients, where chemotherapeutic treatments also generate metabolic deregulation and inhibition of food intake. Patients suffering from cachexia have systemic inflammation, increased energy requirement and altered amino acid metabolism. While the link between inflammation and loss of appetite is well established, the underlying molecular mechanisms are still poorly understood.

Hypothesis
Data from literature and our preliminary results led us to hypothesize that the stress signaling pathway eIF2a/ATF4 may play a role in the etiology of secondary anorexia.

  • In the brain, we showed that this signalling contributes to disrupt the homeostatic regulation of food intake. (Maurin et al., Cell Metab 2005 ) and its pharmacological activation in the hypothalamus induces strong anorexia (Maurin et al. Cell Rep 2014 ).
  • In peripheral tissues, eIF2a/ATF4 signaling can indirectly regulate appetite by controlling the expression of GDF15, a cytokine that is overexpressed in many diseases including cancers  (Baek & Eling, Pharmacol Ther 2019) and has an anorectic action via the activation of specific receptors in the brain stem (Hsu et al., Nature 2017).

Toolbox anorexia


Investigators
Ghita Chaouki, Mélodie Malige, Laurent Parry, Cécile Coudy-Gandilhon, Pierre Fafournoux, Anne-Catherine Maurin

Understand-PI-Coll-Fundings_Anorexia




    Mechanisms of muscle atrophy and resistance models
There is currently no specific treatment to fight against muscle atrophy. Our goals are to understand the molecular mechanisms controlling muscle mass using models of induced atrophy and resistance.
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Our objectives
  • To characterize the development stages of atrophy in mouse models (fasting, physical inactivity...)
  • To understand the mechanisms of resistance to atrophy in a hibernating mammal model
  • To identify new molecular targets and key players in muscle mass control
  • To identify innovative nutritional and/or pharmacological strategies to fight atrophy

Our strategy
  • Comparative approaches of physiological and molecular responses in muscle and other tissues (protein metabolism, signalling pathway, mitochondrial homeostasis)
  • Nutritional/pharmacological preconditioning to preserve muscle mass in vitro and in vivo
  • Transfer of properties of hibernating bear serum to human cells

References

Investigators
Christian Boyer, Lydie Combaret, Cécile Coudy-Gandilhon,  Laura Cussonneau, Christiane Deval, Etienne LefaiAnne-Catherine Maurin, Laurent Parry