title: The mechanistic and ergogenic effects of phosphatidic acid in skeletal muscle.
abstract: Skeletal muscle mass plays a vital role in locomotion, whole-body metabolic health, and is a positive predictor of longevity. It is well established the mammalian target of rapamycin (mTOR) is a central regulator of skeletal muscle protein turnover. The pursuit to find novel nutrient compounds or functional food sources that possess the ability to activate mTOR and promote skeletal muscle protein accretion has been on going. Over the last decade, a key role has been proposed for the phospholipid phosphatidic acid (PA) in mTOR activation. Mechanical load-induced (i.e., resistance exercise) intramuscular PA can directly bind to and activate mTOR. In addition, PA provided exogenously in cell culture heightens mTOR activity, albeit indirectly. Thus, endogenously generated PA and exogenous provision of PA appear to act through distinct mechanisms that converge on mTOR and, potentially, may amplify muscle protein synthesis. In support of this notion, limited evidence from humans suggests that resistance exercise training combined with oral supplemental PA enhances strength gains and muscle hypertrophy. However, the precise mechanisms underpinning the augmented muscle remodelling response with supplemental PA remain elusive. In this review, we will critically examine available evidence from cell cultures and animal and human experimental models to provide an overview of the mechanisms through which endogenous and exogenous PA may act to promote muscle anabolism, and discuss the potential for PA as a therapeutic tool to maintain or restore skeletal muscle mass in the context of ageing and disease.
authors.affiliation: a School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Brandon James
authors.initials: BJ
authors.lastname: Shad
authors.affiliation: a School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Benoit
authors.initials: B
authors.lastname: Smeuninx
authors.affiliation: b MRC-ARUK Centre for Excellence in Musculoskeletal Ageing Research, Birmingham, UK.|c Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital, Nottingham, DE22 3DT, UK.
authors.forename: Philip James
authors.initials: PJ
authors.lastname: Atherton
authors.affiliation: b MRC-ARUK Centre for Excellence in Musculoskeletal Ageing Research, Birmingham, UK.|d School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, UK.
authors.forename: Leigh
authors.initials: L
authors.lastname: Breen
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D006984:Hypertrophy; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D058573:Performance-Enhancing Substances / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000378:metabolism / Q000494:pharmacology*; D055948:Sarcopenia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D058573:Performance-Enhancing Substances; D010712:Phosphatidic Acids; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: acide phosphatidique; hypertrophie; hypertrophy; muscle squelettique; phosphatidic acid; protein synthesis; sarcopenia; sarcopénie; skeletal muscle; synthèse protéique