Model of metabolic fuel use in skeletal muscle during a low plane of nutrition (top panel) or heat stress (bottom panel). During a low plane of nutrition (in thermoneutral conditions, top panel) circulating concentrations of insulin and glucose are reduced whereas plasma fatty acids (FA) are elevated. The myocyte is geared to use FA for energy and circulating glucose use is spared. Activation of the beta-adrenergic receptor (βAR) facilitates glycogenolysis and the release of glucose-1-phosphate (G-1-P). During heat stress conditions, despite a low plane of nutrition, circulating insulin is elevated and plasma FA concentration is reduced. Presumably the myocyte has a reduced capacity to use FA for energy and must rely on glucose (circulating and (or) glycogen) for energy needs. Transported glucose is converted to glucose-6-phosphate (G-6-P) and enters glycolysis. Because of elevated pyruvate dehydrogenase kinase 4 (PDK4) and the corresponding decreased activity of the pyruvate dehydrogenase complex (PDH), substrate flow into the tricarboxylic acid cycle (TCA) is diminished and the cell relies on glycolysis. Lactate efflux increases via pyruvate conversion due to increased lactate dehydrogenase activity (LDH) and likely travels to the liver to serve as a substrate for gluconeogenesis. Hypoxia-inducible factor (HIF-1) may increase PDK4 and LDH during heat stress. An increase in mitochondrial damage and(or) reduced components of the electron transport chain (ETC) would support the increased reliance on carbohydrate and glycolysis for energy. In the diagram, differential substrate and pathway use are portrayed by altered font sizes and line weights.