UNH - Unité de Nutrition Humaine
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Olivier Le Bacquer
Le Bacquer Olivier
olivier.le-bacquer@inrae.fr
04 73 17 82 48
INRAE
ASMS
Researcher

During aging, there is an involuntary decline in muscle mass and a loss of muscle function. This phenomenon, called sarcopenia, has been observed in humans and rodents. This sarcopenia results in reduced mobility in older adults, greater frailty, an increased risk of falls and fractures, and metabolic disorders. Thus, identifying the factors responsible for this muscle loss observed with age is necessary to define ways to preserve muscle mass and function, thereby ensuring the maintenance of health and quality of life in older adults.
The causes of sarcopenia are multiple and include decreased protein synthesis, increased proteolysis, resistance to anabolic signals (amino acids, insulin, etc.), and inadequate or insufficient protein bioavailability. This sarcopenia also results from intrinsic factors involving molecular and cellular alterations, and extrinsic factors such as nutrition or physical activity.
There is considerable variability in muscle mass and strength in older adults, which remains unexplained. Therefore, understanding the mechanisms involved in the development of sarcopenia is important for developing strategies that include preventative nutrition and exercise to maintain muscle mass and help maintain quality of life in older adults.

Research activity

The endocannabinoid system is involved in the control of metabolic homeostasis and is becoming an increasingly popular target for pharmacotherapy. Two types of cannabinoids are distinguished: endocannabinoids produced endogenously by mammals and phytocannabinoids from Cannabis sativa. A growing number of studies have highlighted the involvement of this system in the control of lipid and carbohydrate metabolism, mitochondrial biogenesis and activity, as well as muscle development and metabolism.
Cannabidiol (a phytocannabinoid) possesses antioxidant and anti-inflammatory properties and modulates respiration and mitochondrial dynamics in various cellular models. In addition to these effects, cannabidiol partially restores muscle function in dystrophic mdx mice and attenuates oxidative stress induced by an obesogenic diet in skeletal muscle. The main objective of my research is to characterize the role of this system in the control of skeletal muscle homeostasis in the context of sarcopenia and cachexia. To address this question, we use an in vitro muscle differentiation model (C2C12 cells) and in vivo models using aged rodents or rodents in which cachexia is induced by tumor implantation or chemotherapy treatment (cisplatin).

Most notable publications

  • Le Bacquer O, Sanchez P, Patrac V, Rivoirad C, Saroul N, Giraudet C, Kocer A, Walrand S. Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress.Am J Physiol Cell Physiol 2024 Feb 26. doi: 10.1152/ajpcell.00622.2023.
  • Fajardo L, Sanchez P, Salles J, Rigaudière JP, Patrac V, Caspar-Bauguil S, Bergoglgio C, Moro C, Walrand S, Le Bacquer O. Inhibition of the endocannabinoid system reverses obese phenotype in aged mice and partly restores skeletal muscle function.Am J Physiol Endocrinol Metab 2023 Feb 1. DOI: 10.1152/ajpendo.00258.2022.
  • 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.

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