Know more

About cookies

What is a "cookie"?

A "cookie" is a piece of information, usually small and identified by a name, which may be sent to your browser by a website you are visiting. Your web browser will store it for a period of time, and send it back to the web server each time you log on again.

Different types of cookies are placed on the sites:

  • Cookies strictly necessary for the proper functioning of the site
  • Cookies deposited by third party sites to improve the interactivity of the site, to collect statistics

Learn more about cookies and how they work

The different types of cookies used on this site

Cookies strictly necessary for the site to function

These cookies allow the main services of the site to function optimally. You can technically block them using your browser settings but your experience on the site may be degraded.

Furthermore, you have the possibility of opposing the use of audience measurement tracers strictly necessary for the functioning and current administration of the website in the cookie management window accessible via the link located in the footer of the site.

Technical cookies

Name of the cookie

Purpose

Shelf life

CAS and PHP session cookies

Login credentials, session security

Session

Tarteaucitron

Saving your cookie consent choices

12 months

Audience measurement cookies (AT Internet)

Name of the cookie

Purpose

Shelf life

atid

Trace the visitor's route in order to establish visit statistics.

13 months

atuserid

Store the anonymous ID of the visitor who starts the first time he visits the site

13 months

atidvisitor

Identify the numbers (unique identifiers of a site) seen by the visitor and store the visitor's identifiers.

13 months

About the AT Internet audience measurement tool :

AT Internet's audience measurement tool Analytics is deployed on this site in order to obtain information on visitors' navigation and to improve its use.

The French data protection authority (CNIL) has granted an exemption to AT Internet's Web Analytics cookie. This tool is thus exempt from the collection of the Internet user's consent with regard to the deposit of analytics cookies. However, you can refuse the deposit of these cookies via the cookie management panel.

Good to know:

  • The data collected are not cross-checked with other processing operations
  • The deposited cookie is only used to produce anonymous statistics
  • The cookie does not allow the user's navigation on other sites to be tracked.

Third party cookies to improve the interactivity of the site

This site relies on certain services provided by third parties which allow :

  • to offer interactive content;
  • improve usability and facilitate the sharing of content on social networks;
  • view videos and animated presentations directly on our website;
  • protect form entries from robots;
  • monitor the performance of the site.

These third parties will collect and use your browsing data for their own purposes.

How to accept or reject cookies

When you start browsing an eZpublish site, the appearance of the "cookies" banner allows you to accept or refuse all the cookies we use. This banner will be displayed as long as you have not made a choice, even if you are browsing on another page of the site.

You can change your choices at any time by clicking on the "Cookie Management" link.

You can manage these cookies in your browser. Here are the procedures to follow: Firefox; Chrome; Explorer; Safari; Opera

For more information about the cookies we use, you can contact INRAE's Data Protection Officer by email at cil-dpo@inrae.fr or by post at :

INRAE

24, chemin de Borde Rouge -Auzeville - CS52627 31326 Castanet Tolosan cedex - France

Last update: May 2021

Menu Logo Principal logo Université Clermont Auvergne & associés

Human Nutrition Unit

Zone de texte éditable et éditée et rééditée

Dr Anne-Catherine Maurin

Anne-Catherine Maurin's profile

Field of research

Adaptive mechanisms to an amino acid imbalance stress

Among the 20 amino acids (AA) used for protein synthesis, 9 AA cannot be synthesized de novo and are called are indispensable AA (IAA): valine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, histidine and tryptophan. Furthermore, there is no specific system for storing AA. Consequently, when necessary the organism must hydrolyze endogenous protein to produce free amino acids, at the expense of essential elements.

One stressful condition for the organism is represented by an imbalanced supply of AA in the diet, notably in case of inadequate IAA inputs. Indeed, while the supply of nutrients in the meal is supposed to trigger biosynthesis, the lack of one or several AA hinders anabolic processes. In addition to nutritional factors, various forms of stress (trauma, thermal burn, sepsis, fevers, etc.) or several chronic illnesses (cancer, AIDS, chronic renal, cardiac, hepatic, and pulmonary diseases…) can affect nitrogen metabolism. In such a situation, changes in the patterns of free amino acids are observed in plasma and urine. Therefore, some signalling pathways exist that can detect AA deficits and trigger adaptive processes in order to limit the deleterious effects.

Our goal is to determine how this adaptation takes place, by identifying

1) the molecular mechanisms involved and

2) the cellular and physiological functions that are modulated in response to a nutritional stress.

Research activities

Physiological functions regulated by the GCN2/p-eIF2a/ATF4 pathway

Control of food intake: Omnivorous animals are able to recognize food sources exhibiting IAA imbalances: they will consume substantially less of an otherwise identical meal lacking a single IAA and will search for healthier balanced diets. We have shown that in response to an IAA devoid meal, the brain-specific activation of GCN2 leads to food intake inhibition. More precisely, we have shown that GCN2 activity in the mediobasal hypothalamus controls the onset of the aversive response. Importantly, the sole phosphorylation of eIF2a in this area is sufficient to dramatically inhibit food intake. In addition, rodents have the innate ability to compose a balanced diet from different sources of macronutrients, particularly adapting the protein consumption level to their needs. We have shown that mice change their macronutrient selection profile during ageing and that this phenotype is significantly affected by GCN2 ablation (GCN2 -/- mice greatly reduce their consumption of proteins in favor of lipids).

Autophagy regulation: Animals respond to dietary IAA deficiencies by hydrolyzing body protein in order to produce free AA and maintain their homeostasis. The first tissue to hydrolyze resident protein when AA content is limited is the liver, through the up-regulation of autophagy. Following the consumption of a meal deficient in one IAA, the corresponding IAA concentration in the blood drops rapidly and to a great extent, leading to the activation of the GCN2/p-eIF2a/ATF4 pathway, notably in the liver. Our results show that activation of the GCN2/p-eIF2a/ATF4 pathway is involved in the signaling events of autophagy up-regulation following a lack of IAA.

Publications

Gietzen DW, Anthony TG, Fafournoux P, Maurin AC, Koehnle TJ, Hao S. (2016) Measuring the ability of mice to sense dietary essential amino acid deficiency: the importance of amino acid status and timing. Cell Reports. 16:2049-2050.

Chaveroux C, Bruhat A, Carraro V, Jousse C, Averous J, Maurin AC, Parry L, Mesclon F, Muranishi Y, Cordelier P, Meulle A, Baril P, Do Thi A, Ravassard P, Mallet J, Fafournoux P. (2016) Regulating the expression of therapeutic transgenes by controlled intake of dietary essential amino acids. Nature Biotechnology 34(7):746-51.

Maurin A C, Benani A, Lorsignol A, Brenachot X, Parry L, Carraro V, Guissard C, Averous J, Jousse C, Bruhat A, Chaveroux C, B'Chir W, Muranishi Y, Ron D, Penicaud L and Fafournoux P. (2014) Hypothalamic eIF2alpha signaling regulates food intake. Cell Reports 6:438-444.

B'Chir W, Maurin A C, Carraro V, Averous J, Jousse C, Muranishi Y, Parry L, Stepien G, Fafournoux P and Bruhat A. (2013) The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic acids research 41: 7683-7699.

Maurin A C, Chaveroux C, Lambert-Langlais S, Carraro V, Jousse C, Bruhat A, Averous J, Parry L, Ron D, Alliot J and Fafournoux P. (2012) The amino acid sensor GCN2 biases macronutrient selection during aging. European journal of nutrition 51: 119-126.

Carraro V, Maurin A C, Lambert-Langlais S, Averous J, Chaveroux C, Parry L, Jousse C, Ord D, Ord T, Fafournoux P and Bruhat A. (2010) Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2alpha/ATF4 pathway. PLoS One 5: e15716.

Jousse C, Deval C, Maurin AC, Parry L, Chérasse Y, Chaveroux C, Lefloch R, Lenormand P, Bruhat A and Fafournoux P. (2007) TRB3 inhibits the transcriptional activation of stress-regulated genes by a negative feedback on the ATF4 pathway. Journal of Biological Chemistry 282:15851-61.

Maurin AC, Jousse C, Averous J, Parry L, Bruhat A, Cherasse Y, Zeng H, Zhang Y, Harding HP, Ron D and Fafournoux P. (2005) The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metabolism 1:273-7.

back