Fig. 2

Cellular mechanisms by which EPA and DHA impact muscle protein synthesis and breakdown. Amino acids promote muscle protein synthesis via mammalian target of rapamycin (mTOR). Inflammation promotes muscle protein breakdown, partly through upregulation of the ubiquitin–proteasome system; inflammation also decreases protein synthesis through inhibition of mTOR. EPA and DHA have multiple anti-inflammatory actions and also promote inflammation resolution. Extracellular EPA and DHA are incorporated into muscle cell membrane phospholipids from where they may be released and act as substrates for specialized pro-resolution mediators (SPMs). Extracellular EPA and DHA can act as ligands for G-protein coupled receptors (GPCRs) especially GPCR120. Subsequent signalling inhibits activation of the pro-inflammatory transcription factor nuclear factor kappa B (NFκB). EPA and DHA also inhibit NFκB activation, probably via membrane-mediated actions, and they activate peroxisome proliferator-activated receptors (PPARs), which physically interfere with NFκB translocation to the nucleus. NFκB upregulates synthesis of genes encoding many proteins involved in the inflammatory response including multiple cytokines, chemokines, cyclooxygenase (COX)-2, and matrix metalloproteinases (MMPs) and upregulates muscle ring finger protein (MuRF) which activates the ubiquitin–proteasome system. Hence, the anti-inflammatory and inflammation resolving actions of EPA and DHA act to promote muscle protein synthesis and to decrease muscle protein breakdown. There is also evidence that EPA and DHA activate the mTOR pathway