Extreme or unaccustomed eccentric exercise can cause exercise-induced muscle damage, characterized by structural changes involving sarcomere, cytoskeletal, and membrane damage, with an increased permeability of sarcolemma for proteins. From a functional point of view, disrupted force transmission, altered calcium homeostasis, disruption of excitation-contraction coupling, as well as metabolic changes bring about loss of strength. Importantly, the trauma also invokes an inflammatory response and clinically presents itself by swelling, decreased range of motion, increased passive tension, soreness, and a transient decrease in insulin sensitivity. While being damaging and influencing heavily the ability to perform repeated bouts of exercise, changes produced by exercise-induced muscle damage seem to play a crucial role in myofibrillar adaptation. Additionally, eccentric exercise yields greater hypertrophy than isometric or concentric contractions and requires less in terms of metabolic energy and cardiovascular stress, making it especially suitable for the elderly and people with chronic diseases. This review focuses on our current knowledge of the mechanisms underlying exercise-induced muscle damage, their dependence on genetic background, as well as their consequences at the structural, functional, metabolic, and clinical level. A comprehensive understanding of these is a prerequisite for proper inclusion of eccentric training in health promotion, rehabilitation, and performance enhancement.

• MeSH
• Pain etiology   metabolism   pathology   MeSH
• Exercise physiology   MeSH
• Muscle, Skeletal injuries   metabolism   physiopathology   MeSH
• Humans MeSH
• Muscle Contraction physiology   MeSH
• Inflammation etiology   metabolism   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

• Keywords
• Mitochondrial respiration, Mitochondrial uncoupling, PPARδ, PPARδ agonist, Saturated fatty acid, Skeletal muscle cells, Unsaturated fatty acids,
• MeSH
• Cell Death drug effects   MeSH
• Cell Line MeSH
• Dietary Fats, Unsaturated pharmacology   MeSH
• Muscle, Skeletal drug effects   metabolism   MeSH
• Palmitic Acid toxicity   MeSH
• Mice MeSH
• Receptors, Cytoplasmic and Nuclear metabolism   MeSH
• Gene Expression Regulation, Enzymologic drug effects   MeSH
• Sulfones pharmacology   MeSH
• Muscle Cells drug effects   metabolism   MeSH
• Thiazoles pharmacology   MeSH
• Thiophenes pharmacology   MeSH
• Cell Survival MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Dietary Fats, Unsaturated MeSH
• GSK0660 MeSH Browser
• GW 501516 MeSH Browser
• Palmitic Acid MeSH
• Ppard protein, mouse MeSH Browser
• Receptors, Cytoplasmic and Nuclear MeSH
• Sulfones MeSH
• Thiazoles MeSH
• Thiophenes MeSH