Regulation of Lipolysis in Severely Burned Children

Abstract

In this study, the rates of lipid mobilization and of lipolysis have been quantified in severely burned children. In all 12 patients studied, the basal rates were determined. In seven patients, the lipolytic responsiveness to an infusion of epinephrine (0.015 micrograms/kg/min) was tested, and in the other five patients, the response to beta-adrenergic blockade (propranolol, 1 mg/kg) was tested. The rate of appearance (Ra) of free fatty acids (FFA) was quantified by means of the infusion of 1-13C-palmitate to determine the rate of lipid mobilization, and Ra glycerol was determined using d5-glycerol to assess the rate of lipolysis more directly. In five patients, body composition was determined after recovery by means of H2(18)O dilution. The basal rate of lipolysis was higher than normal in the burned children. In four of the seven patients infused with epinephrine, there was a pronounced increase in Ra glycerol. In all patients given beta-blockade, Ra glycerol decreased greatly. Changes in Ra FFA corresponded with the changes in Ra glycerol in each case. Total body fat was very low (approximately 2% body weight), reflecting the surgical removal of fat in the process of burn wound excision. From these data it is concluded that lipolytic responsiveness to catecholamines in severely burned children is variable, but not absent, despite chronically elevated levels of catecholamines. The total extent of lipolysis may be limited by the available fat mass in children treated with fascial excision. In such patients, the limitation in the ability to mobilize an adequate amount of FFA to fully meet energy requirements provides an important rationale for the clinical practice of providing nutritional support in hourly boluses, as opposed to infrequent meals, since any period of even a few hours in which nutrients are not being absorbed will result in an energy substrate deficiency and consequent increase in amino acid oxidation.

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

“…To provide glucose, a major fuel source to vital organs, release of the above-mentioned stress mediators oppose the anabolic actions of insulin (74). By enhancing adipose tissue lipolysis (75) and skeletal muscle proteolysis (76), they increase gluconeogenic substrates, including glycerol, alanine, and lactate, thus augmenting hepatic glucose production in burn patients (72,73,77). Hyperglycemia fails to suppress hepatic glucose release during this time (23), and the suppressive effect of insulin on hepatic glucose release is attenuated, significantly contributing to posttrauma hyperglycemia (78).…”

“…Cree et al (69) showed an impaired activation of Insulin Receptor Substrate-1 at its tyrosine binding site and an inhibition of Akt in muscle biopsies of children at 7 days postburn. The work of Wolfe et al (23,75,78,80) indicates links between impaired liver and muscle mitochondrial oxidative function, altered rates of lipolysis, and impaired insulin signaling postburn, attenuating both the suppressive actions of insulin on hepatic glucose production and on the stimulation of muscle glucose uptake. Another counterregulatory hormone of interest during stress of the critically ill is glucagon.…”

The Hepatic Acute Phase Response to Thermal Injury

“…In order to provide glucose, a major fuel source to vital organs, release of the above mentioned stress mediators oppose the anabolic actions of insulin (74). By enhancing adipose tissue lipolysis (75) and skeletal muscle proteolysis (76), they increase gluconeogenic substrates, including glycerol, alanine and lactate, thus augmenting hepatic glucose production in burned patients (72,73,77). Hyperglycemia fails to suppress hepatic glucose release during this time (23) and the suppressive effect of insulin on hepatic glucose release is attenuated, significantly contributing to post-trauma hyperglycemia (78).…”

“…Cree et al (69) showed an impaired activation of Insulin Receptor Substrate-1 at its tyrosine binding site and an inhibition of Akt in muscle biopsies of children at seven days post-burn. Work of Wolfe et al (23,75,78,80) indicates links between impaired liver and muscle mitochondrial oxidative function, altered rates of lipolysis, and impaired insulin signaling post-burn attenuating both the suppressive actions of insulin on hepatic glucose production and on the stimulation of muscle glucose uptake. Another counter-regulatory hormone of interest during stress of the critically ill is glucagon.…”

Sepsis as a modulator of adaptation to low and high carbohydrate and low and high fat intakes

“…It has been reported that there was no relation between the type of nutritional support and the extent of fat in®ltration in the liver (Wolfe et al, 1988b). Since the extent of increase in lipolysis in stressed patients is a function of the magnitude of sympathetic nervous system response (Wolfe et al, 1987b), it is possible that there is a direct link between the degree of stress and the rate of hepatic triglyceride production, irrespective of the nature of nutritional support. It is also possible that neither FFA appearance or de novo synthesis of fatty acids is the cause of hepatic fat accumulation.…”