Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of “work-induced hypertrophy” in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.

The goal of this critical review is to comprehensively assess the evidence for the molecular, physiologic, and phenotypic skeletal muscle responses to

Mitochondrial membrane lipids adapt to exercise or disuse, underscoring an essential role for PE in energy transduction.

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

Background: Mechanisms underlying physical inactivity‐induced insulin resistance are not well understood. In addition to a role in muscle repair, immune cell populations such as macrophages may regulate insulin sensitivity.Aim: The aim of this study was to examine if the dynamic changes in insulin sensitivity during and after recovery from reduced physical activity corresponded to changes in skeletal muscle macrophages.Methods: In this prospective clinical study, we collected muscle biopsies from healthy older adults (70 ± 2 years, n = 12) before and during a hyperinsulinaemic‐euglycaemic clamp and this occurred before (PRE) and after 2‐week reduced physical activity (RA), and following 2‐week of recovery (REC). Insulin sensitivity (hyperinsulinaemic‐euglycaemic clamp), skeletal muscle mRNA expression of inflammatory markers, and immunofluorescent quantification of skeletal muscle macrophages, myofibre‐specific satellite cell and capillary content were assessed.Results: Insulin sensitivity was decreased following reduced activity and rebounded following recovery above PRE levels. We observed an increase (P < 0.01) in muscle macrophages (CD68⁺CD206⁺: 190 [55, 324]; CD11b⁺CD206⁺: 117 [28, 205]% change from PRE) and CD68 (2.4 [1.4, 3.4]‐fold) and CCL2 (1.9 [1.3, 2.5]‐fold) mRNA following RA concurrent with increased (P < 0.03) satellite cells (55 [6, 104]%) in slow‐twitch myofibres. Moreover, the distance of satellite cells to the nearest capillary was increased 7.7 (1.7, 13.7) µm in fast‐twitch myofibres at RA (P = 0.007). Changes in macrophages were positively associated with increased insulin sensitivity following RA (R > 0.57, P < 0.05).Conclusion: These findings suggested that a dynamic response of skeletal muscle macrophages following acute changes in physical activity in healthy older adults is related to insulin sensitivity.