Journal of Sports Medicine & Doping Studies

Molecular Determinants of Skeletal Muscle Hypertrophy in Animals

Abstract

Kunihiro Sakuma and Akihiko Yamaguchi

Beyond skeletal muscle’s primary function as a force generator for locomotion, there is a growing recognition of the important role skeletal muscle plays in overall health through its impact on whole-body metabolism as well as directly influencing quality of life issues with chronic disease and aging. Over the last decade, extensive progress has been made with regard to our understanding of the molecules that regulate skeletal muscle mass. Various growth factors such as insulin-like growth factor-I (IGF-I), hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) have been shown to stimulate the activation, proliferation, and differentiation of satellite cells, and then contribute to muscle hypertrophy as well as normal muscle growth. In contrast, myostatin inhibits these processes through forkhead box O (FOXO) and/or Smad 2/3-dependent signaling. Intramuscular signaling by PI3-K/Akt/mTOR, calcineurin, and serum response factor (SRF) activates protein synthesis but some signaling also inhibits protein degradation at the same time. Although various studies using in vitro cell cultures and in vivo rodent models have revealed candidates for proteins that modulate the hypertrophic process in muscle fibers after mechanical loading, these findings do not necessarily apply to the adaptations that occur in human muscle. In this review, we discuss several possible factors regulating muscle hypertrophy, and the adaptations of human muscle after resistance training, a model of mechanical loading.