On the regulation of energy expenditure in man

Abstract

The present study was performed to examine the role of body composition, obstructive sleep apnea, (OSA) thyroid hormones, growth hormone (GH) and leptin on energy expenditure (EE) regulation in man and to evaluate the use of the amino-terminal pro-collagen III peptide (PIIIp) as a marker of EE. EE was determined by means of indirect calorimetry in a ventilated open-hood system and in a chamber for indirect calorimetry.In a large group of euthyroid individuals, the relationships between EE and body composition, thyroid hormones and PIIIp were examined. Basal metabolic rate (BMR) was higher in males than females. However, fat-free mass (FFM) was higher in men and, after adjustments for FFM, no gender-difference in terms of BMR was observed. BMR was positively correlated to FFM, body fat (BF), total T3, the free T3/free T4 ratio and PIIIp and negatively correlated to free T4 (men) and the ratios between free T3/total T3 and free T4/total T4. PIIIp was as strongly related to BMR as total T3. More than 80% of the variation in BMR was explained by the included variables.The effects of sleep disordered breathing disturbances on EE were examined in a small sample of subjects with OSA (n=5). Subjects with OSA had a higher 24h EE than controls (p<0.05). Treatment with continuous positive airway pressure (CPAP) normalized sleep and decreased sleeping EE (p<0.05), variability in EE during sleep (p<0.05) and serum concentrations of PIIIp (p<0.05). The CPAP treatment increased the ratio between daytime EE and sleep EE (p<0.05).The long-term effects of GH on EE in subjects with GH deficiency (GHD) were examined in a randomized, double-blind and placebo-controlled trial over 6 months. Baseline BMR was in the lower part of the reference range, but, when compared with a carefully matched control group, no significant difference was observed in BMR or BMR adjusted for FFM. During GH treatment, BMR increased by 18% (p<0.001). Between 6 weeks and 26 weeks no further change in BMR was observed. The increase in BMR could not solely be explained by changes in FFM, as there was also an increase in BMR adjusted for FFM after 6 weeks which was maintained after 26 weeks. The increase in BMR was associated with changes in T3, PIIIp and free fatty acids (FFA).The short-term effects of GH treatment on 24h EE in GHD were examined in an open trial over 4 weeks. During the first 2 weeks, 24h EE (p<0.05), SMR (p<0.05) and BMR (p<0.05) increased. No change was seen in daytime EE. The increase in EE was associated with changes in insulin-like growth factor I, insulin-like growth factor-binding protein 3, the free T3/free T4 ratio and PIIIp but not with changes in body composition.The effects of GH treatment on EE and the leptin system were examined in a random-ized, double-blind, placebo-controlled study over 9 months of men with abdominal obesity. During GH treatment, serum leptin decreased over 6 weeks (12.5±4.8 v 10.3±4.3 µg/L). A similar decrease in serum leptin was also found after making adjustments for BF. After 9 months, serum leptin levels had returned to baseline levels in spite of clear effects on body composition. No effect was found on leptin mRNA levels. The long-term changes in serum leptin concentrations were correlated with changes in EE, independent of changes in BF.It is concluded that cross-sectional variation in EE can be largely explained by differ-ences in FFM and thyroid hormones in an euthyroid population. OSA has a major effect on EE, particularly during sleep. Treatment with GH increases EE independently of changes in body composition. The increase in EE occurs during the first 2 weeks of treatment and co-varies with several metabolic factors. GH treatment also induces changes in the leptin system with potential effects on the regulation of EE. PIIIp was closely related to EE and may thus serve as an indicator of EE.