Publications

Latest publication 02/04/2019

4E_BP1 and 4E_BP2 double knockout mice are protected from aging_associated sarco

Background Sarcopenia is the loss of muscle mass/function that occurs during the aging process. The links between mechanistic target of rapamycin...

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    [title] => 4E_BP1 and 4E_BP2 double knockout mice are protected from aging_associated sarco
    [paragraph] => 4E_BP1 and 4E_BP2 double knockout mice are protected from aging_associated sarcopenia
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Authors
O Le Bacquer, K Combe, V Patrac, B Ingram et al

 Lab
INRA, UMR 1019 , UniversitŽ Clermont Auvergne, UNH, UnitŽ de Nutrition Humaine, CRNH Auvergne, F63000 , Clermont-Ferrand, France
Journal
Journal of Cachexia, Sarcopenia and Muscle 
Abstract
Background Sarcopenia is the loss of muscle mass/function that occurs during the aging process. The links between mechanistic target of rapamycin (mTOR) activity and muscle development are largely documented, but the role of its downstream targets in the development of sarcopenia is poorly understood. Eukaryotic initiation factor 4E-binding proteins (4E-BPs) are targets of mTOR that repress mRNA translation initiation and are involved in the control of several physiological processes. However, their role in skeletal muscle is still poorly understood. The goal of this study was to assess how loss of 4E-BP1 and 4E-BP2 expression impacts skeletal muscle function and homeostasis in aged mice and to characterize the associated metabolic changes by metabolomic and lipidomic proÞling. 
Methods Twenty-four-month-old wild-type and whole body 4E-BP1/4E-BP2 double knockout (DKO) mice were used to measure muscle mass and function. Protein homeostasis was measured ex vivo in extensor digitorum longus by incorporation of L[U-14C]phenylalanine, and metabolomic and lipidomic proÞling of skeletal muscle was performed by Metabolon, Inc. 
Results The 4E-BP1/2 DKO mice exhibited an increase in muscle mass that was associated with increased grip strength (P < 0.05). Protein synthesis was higher under both basal (+102%, P < 0.05) and stimulated conditions (+65%, P < 0.05) in DKO skeletal muscle. Metabolomic and complex lipid analysis of skeletal muscle revealed robust differences pertaining to amino acid homeostasis, carbohydrate abundance, and certain aspects of lipid metabolism. In particular, levels of most free amino acids were lower within the 4E-BP1/2 DKO muscle. Interestingly, although glucose levels were unchanged, differences were observed in the isobaric compound maltitol/lactitol (33-fold increase, P < 0.01) and in several additional carbohydrate compounds. 4E-BP1/2 depletion also resulted in accumulation of medium-chain acylcarnitines and a 20% lower C2/C0 acylcarnitine ratio (P < 0.01) indicative of reduced _-oxidation. 
Conclusions Taken together, these Þndings demonstrate that deletion of 4E-BPs is associated with perturbed energy metabolism in skeletal muscle and could have beneÞcial effects on skeletal muscle mass and function in aging mice. They also identify 4E-BPs as potential targets for the treatment of sarcopenia.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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