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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

Olivier LE BACQUER, PhD

Activities

Email : contact
Tel : +33 (0)4 73 60 82 58

During aging, an involuntary decline in skeletal muscle mass and impaired muscle function called sarcopenia, has been described in both human and rodents. It is associated with an increased risk of physical disability, falls, fractures, metabolic alterations and frailty. Therefore the prevention of age-related losses in muscle mass and strength is of importance in order to maintain physical capacities at older age, preserve an independent living and a better quality of life as long as possible.

The pathophysiology of sarcopenia is complex and involves increased muscle proteolysis, reduced muscle protein synthesis, resistance to anabolic stimuli including insulin and amino acids and a reduced or inadequate bioavailability of amino acids mainly due to an increased splanchnic sequestration. In addition, this phenomenon is also the result of both intrinsic factors involving changes at molecular and cellular levels, and extrinsic or environmental factors such as nutrition and exercise.

Considerable unexplained variations in muscle strength and mass among older persons exist. Therefore understanding the mechanism responsible for the development of sarcopenia is of great importance to help to develop optimal preventive nutritional and exercise strategies to maintain muscle mass and function in order to preserve muscle quality, prevent loss in physical capacities and maintain a good quality of life for elderly.

Research Activities

Role of 4E-BP proteins on muscle mass homeostasis and sarcopenia: the mTOR pathway (mammalian target of rapamycin) has a central role in the control of muscle protein homeostasis and mitochondrial activity in tissues. In response to various anabolic stimuli such as amino acids and growth hormones, mTOR stimulates protein synthesis by inhibiting the action of 4E-BP proteins (a family of 3 proteines that inhibit mRNA translation initiation) and by stimulating the activity of S6K1. Studies clearly demonstrated that ageing was associated with alterations in the mTOR pathway in skeletal muscle and genetically engineered mouse models clearly demonstrated the role of mTOR and some other components of the mTOR pathway (TSC, Rheb, Raptor…) on the development of myopathies.

The main objective of my research is to characterize the role of 4E-BP proteins on skeletal muscle and the development of sarcopenia. To answer this question, we are using an in vitro model of muscle differentiation (C2C12 cells) and an in vivo model using whole body double knockout mice for 4E-BP1 and 4E-BP2.

Selected Publications

  • Le Bacquer O, Salles J, Piscitelli F, Sanchez P, Martin V, Montaurier C, Di Marzo V, Walrand S. Alterations of the endocannabinoid system and circulating and peripheral tissue levels of endocannabinoids in sarcopenic rats. J Cachexia Sarcopenia Muscle. 2021 Dec 2. doi: 10.1002/jcsm.12855.
  • Le Bacquer O, Lanchais K, Combe K, Van Den Berghe L, Walrand S. Acute rimonabant treatment promotes protein synthesis in C2C12 myotubes through a CB1-independent mechanism. J Cell Physiol. 2020 Sep 3. doi: 10.1002/jcp.30034.
  • Le Bacquer O, Combe K, Patrac V, Ingram B, Combaret L, Dardevet D, Montaurier C, Salles J, Giraudet C, Guillet C, Sonenberg N, Boirie Y, Walrand S. 4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia. J Cachexia Sarcopenia Muscle. 2019 Mar 29. doi: 10.1002/jcsm.12412.
  •  Le Bacquer O, Combe K, Montaurier C, Salles J, Giraudet C, Patrac V, Domingues-Faria C, Guillet C, Louche K, Boirie Y, Sonenberg N, Moro C, Walrand S. Muscle metabolic alterations induced by genetic ablation of 4E-BP1 and 4E-BP2 in response to diet-induced obesity. Mol Nutr Food Res. 2017 Sep;61(9).
  • Le Bacquer O, Queniat G, Gmyr V, Kerr-Conte J, Lefebvre B, Pattou F. mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells. J Endocrinol. 2013 Jan 2;216(1):21-9.
  • Carnevalli LS, Masuda K, Frigerio F, Le Bacquer O, Um SH, Gandin V, Topisirovic I, Sonenberg N, Thomas G, Kozma SC. S6K1 plays a critical role in early adipocyte differentiation. Dev Cell. 2010 May 18;18(5):763-74.
  • Petroulakis E, Parsyan A, Dowling RJ*, Le Bacquer O*, Martineau Y*, Bidinosti M, Larsson O, Alain T, Rong L, Mamane Y, Paquet M, Furic L, Topisirovic I, Shahbazian D, Livingstone M, Costa-Mattioli M, Teodoro JG, Sonenberg N. p53-dependent translational control of senescence and transformation via 4E-BPs. Cancer Cell. 2009 Nov 6;16(5):439-46.
  • Le Bacquer O, Petroulakis E, Paglialunga S, Poulin F, Richard D, Cianflone K, Sonenberg N. Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. J Clin Invest. 2007 Feb;117(2):387-96.

Curriculum Vitae

Degrees:
 - PhD in Physiology and Nutrition, Université de Nantes (2002)
 - Post-Doctoral training:
      Department of Biochemistry, McGill University, Montréal, Canada (2003-2007)
      European Genomic Institute for Diabetes (EGID), Lille, France (2007-2012)

 Awards and Grants:

- Research Grant ANSSD-INRA (2022)
- Research Grant from the iSITE program (2019-2020)
- Research Grant ANSSD-INRA (2017)
- Research Grant Omique-INRA (2017)
- Research Grant from Région Auvergne (2014-2017)
- Research Grant from the French Society for Parenteral and Enteral Nutrition SFNEP-NUTRICIA (2013)
- McGill Chemical Biology postdoctoral fellowship (2004)
- Research Grant from the French Society for Parenteral and Enteral Nutrition SFNEP-NUTRICIA (2002)
- Research Grant from the European Society for Parenteral and Enteral Nutrition ESPEN–BAXTER (2001)
- ESPEN Young scientist travel award (2001)
- Ph.D. Scholarship from the Ministère de l’Education et de la Recherche (1998-2001)