Effect of Severe Burn Injury on Substrate Cycling by Glucose and Fatty Acids

Abstract

Increases in metabolic rate and core temperature are common responses to severe injury. We have investigated the hypothesis that these responses are due to increases in substrate cycling. A substrate cycle exists when opposing, nonequilibrium reactions catalyzed by different enzymes are operating simultaneously. At least one of the reactions must involve the hydrolysis of ATP. Thus, a substrate cycle both liberates heat and increases energy expenditure, yet there is not net conversion of substrate to product. In studies in volunteers (n = 18) and in patients with severe burns who were in a hypermetabolic state (n = 18), we used stable-isotope tracers to quantify substrate cycling in the pathways of glycolysis and gluconeogenesis and a cycle involving the simultaneous breakdown and synthesis of stored triglyceride (triglyceride-fatty acid cycle). The total rates of triglyceride-fatty acid and glycolytic-gluconeogenic cycling were elevated in the patients by 450 and 250 percent, respectively (P less than 0.01). An infusion of propranolol in the patients greatly reduced triglyceride-fatty acid cycling but did not affect gluconeogenic-glycolytic cycling. We conclude that increased substrate cycling contributes to the increased thermogenesis and energy expenditure following severe burns and that the increased triglyceride-fatty acid cycling is due to beta-adrenergic stimulation.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

“…However, after 48 hours of fasting, liver glycogen is reduced and the body mobilizes fat and proteins to meet the metabolic need. In the muscle, mainly alanine is mobilized which then is converted to glucose by the liver (23,24).…”

Thermic effect of food and sympathetic nervous system activity in humans

“…This part of the TEF of intravenous glucose which can be suppressed by betaadrenergic antagonists has been called 'facultative thermogenesis' (Acheson et al, 1984). Activation by the sympathetic nervous system of energy-requiring processes, such as the Cori cycle (Kusaka and Ui, 1977) and the lipolysis-reesterification of free fatty acids (Wolfe et al, 1987;Breitenstein et al, 1990), is likely to be involved in this facultative portion of TEF. However, it was shown that a 2 week treatment with beta-adrenergic antogonists did not alter the overall energy expenditure of healthy humans (Acheson et al, 1988).…”

Glyceroneogenesis and the Triglyceride/Fatty Acid Cycle

“…Almost 30 years ago, Newsholme and Crabtree (3) discussed the importance of this cycle in metabolic regulation and heat production. Quantitative estimates of the triglyceride/fatty acid cycle in human adults and newborn infants and studies in animals show that only a small fraction of the FFA released as a result of lipolysis in the WAT are oxidized, and the majority are re-esterified to triglycerides in various tissues (2)(3)(4)(5)(6)(7)(8)(9). The quantitative estimates of triglyceride/fatty acid cycling vary in different studies in humans, depending upon the methodology employed.…”