SHORT COMMUNICATION The amino acid sensor GCN2 biases macronutrient selection during aging Anne-Catherine Maurin • Ce ´dric Chaveroux • Sarah Lambert-Langlais • Vale ´rie Carraro • Ce ´line Jousse • Alain Bruhat • Julien Averous • Laurent Parry • David Ron • Josette Alliot • Pierre Fafournoux Received: 20 January 2011 / Accepted: 9 May 2011 / Published online: 26 May 2011 Ó Springer-Verlag 2011 Abstract Purpose Selection of a balanced diet has a determinant impact on human health. Individual food preferences involve socio-cultural as well as physiological factors and evolve during aging. In mammals, physiological mecha- nisms governing food choices appear to require the sensing of nutrient concentrations in diet. This is particularly the case for dietary amino acids that are sensed by the protein kinase GCN2. It has been reported that GCN2 is involved in the adaptive response to amino acid imbalanced diets at the level of food intake and lipid metabolism. Here, we hypothesized that GCN2 may play a role in macronutrient selection and its age-related changes. Methods Two groups of wild-type and GCN2 knock-out mice were subjected to a food self-selection protocol at ages 6, 12, 18 and 24 months. During each test, mice were allowed to create their own diets by selecting between three separate food sources, each containing either protein, fat or carbohydrates. Results Our results show that the absence of GCN2 had two main age-related effects. First, it exacerbated fat preference at the expense of carbohydrate consumption. Second, it prevented the increase in protein intake. Conclusion These findings indicate that, in omnivores, the GCN2 ancient pathway participates in the control of food preference. Keywords Diet selection Á Aging Á GCN2 Á Macronutrient Á Ingestive behavior Introduction Feeding behavior can be considered as an important homeostatic mechanism that contributes to survival. This is illustrated by the innate ability of higher animals to pre- cisely regulate their intake of macronutrients in order to ensure the consumption of a balanced diet [1–3]. This regulation is particularly important for omnivores that must choose among a variety of available food sources to rec- ognize appropriate ones and select from among them to obtain a nutritionally adequate diet [4, 5]. In the particular case of humans living in industrialized countries, while food availability has expanded and become more diversi- fied, there have also been significant negative consequences in terms of inappropriate dietary patterns. This has led to an increase in the occurrence of diet-related chronic diseases during aging, such as obesity, diabetes and cardiovascular diseases. Thus, understanding the underlying mechanisms of macronutrient selection is of considerable interest to improve feeding behavior and promote healthy aging. In humans, the determination of food selection, and hence nutrient intake, is multifactorial in nature and involves both social, psychosocial, cultural factors and more primitive A.-C. Maurin Á C. Chaveroux Á S. Lambert-Langlais Á V. Carraro Á C. Jousse Á A. Bruhat Á J. Averous Á L. Parry Á P. Fafournoux (&) Unite ´ mixte de Recherche 1019, Unite ´ de Nutrition Humaine, Institut National de la Recherche Agronomique, Centre de Clermont-Ferrand/Theix, 63122 Saint Gene `s Champanelle, France e-mail: pierre.fafournoux@clermont.inra.fr D. Ron Skirball Institute of Biomolecular Medecine, New York University School of Medecine, New York, NY 10016, USA J. Alliot Laboratoire de Neuroendocrinologie du Vieillissement, Universite ´ Blaise Pascal, 24 rue des Landais, 63177 Aubie `re Cedex, Clermont-Ferrand, France 123 Eur J Nutr (2012) 51:119–126 DOI 10.1007/s00394-011-0205-4