Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g). Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycemic clamp, 70–90% of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70% of maximal oxygen uptake () and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favor glycogen repletion and preparation for new “fight or flight” events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channeled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type 2 diabetes.

In obesity, excessive abdominal fat, especially the accumulation of visceral adipose tissue (VAT), increases the risk of metabolic disorders, such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and non-alcoholic fatty liver disease. Excessive abdominal fat is associated with adipose tissue dysfunction, leading to systemic low-grade inflammation, fat overflow, ectopic lipid deposition, and reduced insulin sensitivity. Physical activity is recommended for primary prevention and treatment of obesity, T2DM, and related disorders. Achieving a stable reduction in body weight with exercise training alone has not shown promising effects on a population level. Because fat has a high energy content, a large amount of exercise training is required to achieve weight loss. However, even when there is no weight loss, exercise training is an effective method of improving body composition (increased muscle mass and reduced fat) as well as increasing insulin sensitivity and cardiorespiratory fitness. Compared with traditional low-to-moderate-intensity continuous endurance training, high-intensity interval training (HIIT) and sprint interval training (SIT) are more time-efficient as exercise regimens and produce comparable results in reducing total fat mass, as well as improving cardiorespiratory fitness and insulin sensitivity. During high-intensity exercise, carbohydrates are the main source of energy, whereas, with low-intensity exercise, fat becomes the predominant energy source. These observations imply that HIIT and SIT can reduce fat mass during bouts of exercise despite being associated with lower levels of fat oxidation. In this review, we explore the effects of different types of exercise training on energy expenditure and substrate oxidation during physical activity, and discuss the potential effects of exercise training on adipose tissue function and body fat distribution.

ERα gene expression is heritable in humans and prevents obesity in mice by improving mitochondrial function via adipocyte Polg1 expression.

Skeletal muscle protein synthesis rate decreases during contractions but the underlying regulatory mechanisms are poorly understood. It was hypothesized that there would be a coordinated regulation of eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E‐binding protein 1 (4EBP1) phosphorylation by signalling cascades downstream of rises in intracellular [Ca²⁺] and decreased energy charge via AMP‐activated protein kinase (AMPK) in contracting skeletal muscle. When fast‐twitch skeletal muscles were contracted ex vivo using different protocols, the suppression of protein synthesis correlated more closely with changes in eEF2 than 4EBP1 phosphorylation. Using a combination of Ca²⁺ release agents and ATPase inhibitors it was shown that the 60–70% suppression of fast‐twitch skeletal muscle protein synthesis during contraction was equally distributed between Ca²⁺ and energy turnover‐related mechanisms. Furthermore, eEF2 kinase (eEF2K) inhibition completely blunted increases in eEF2 phosphorylation and partially blunted (i.e. 30–40%) the suppression of protein synthesis during contractions. The 3‐ to 5‐fold increase in skeletal muscle eEF2 phosphorylation during contractions in situ was rapid and sustained and restricted to working muscle. The increase in eEF2 phosphorylation and eEF2K activation were downstream of Ca²⁺–calmodulin (CaM) but not other putative activating factors such as a fall in intracellular pH or phosphorylation by protein kinases. Furthermore, blunted protein synthesis and 4EBP1 dephosphorylation were unrelated to AMPK activity during contractions, which was exemplified by normal blunting of protein synthesis during contractions in muscles overexpressing kinase‐dead AMPK. In summary, in fast‐twitch skeletal muscle, the inhibition of eEF2 activity by phosphorylation downstream of Ca²⁺–CaM–eEF2K signalling partially contributes to the suppression of protein synthesis during exercise/contractions.

Insulin-stimulated glucose uptake and incorporation of glucose into skeletal muscle glycogen contribute to physiological regulation of blood glucose concentration. In the present study, glucose handling and insulin signaling in isolated rat muscles with low glycogen (LG, 24-h fasting) and high glycogen (HG, refed for 24 h) content were compared with muscles with normal glycogen (NG, rats kept on their normal diet). In LG, basal and insulin-stimulated glycogen synthesis and glycogen synthase activation were higher and glycogen synthase phosphorylation (Ser⁶⁴⁵, Ser⁶⁴⁹, Ser⁶⁵³, Ser⁶⁵⁷) lower than in NG. GLUT4 expression, insulin-stimulated glucose uptake, and PKB phosphorylation were higher in LG than in NG, whereas insulin receptor tyrosyl phosphorylation, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity, and GSK-3 phosphorylation were unchanged. Muscles with HG showed lower insulin-stimulated glycogen synthesis and glycogen synthase activation than NG despite similar dephosphorylation. Insulin signaling, glucose uptake, and GLUT4 expression were similar in HG and NG. This discordant regulation of glucose uptake and glycogen synthesis in HG resulted in higher insulin-stimulated glucose 6-phosphate concentration, higher glycolytic flux, and intracellular accumulation of nonphosphorylated 2-deoxyglucose. In conclusion, elevated glycogen synthase activation, glucose uptake, and GLUT4 expression enhance glycogen resynthesis in muscles with low glycogen. High glycogen concentration per se does not impair proximal insulin signaling or glucose uptake. “Insulin resistance” is observed at the level of glycogen synthase, and the reduced glycogen synthesis leads to increased levels of glucose 6-phosphate, glycolytic flux, and accumulation of nonphosphorylated 2-deoxyglucose.