β-Adrenoceptor-mediated thermogenesis and lipolysis in patients with chronic obstructive pulmonary disease

Schiffelers, S.L.H.; Blaak, Ellen E.; Baarends, E.M.; Baak, Marleen A. van; Wouters, Emiel F.M.; Schols, A.M.W.J.

doi:10.1152/ajpendo.2001.280.2.e357

Cited by 20 publications

(17 citation statements)

References 40 publications

(45 reference statements)

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“…Although no abnormal plasma glucose levels were found in COPD in the current study, the current authors have previously reported the presence of hyperinsulinaemia in moderate-to-severe COPD patients [34]. Impaired glucose tolerance and impaired b-adrenoceptor-mediated lipolysis have been shown for COPD [35,36]. Furthermore, reduced activities of enzymes involved in oxidative substrate metabolism have been found in the vastus lateralis of COPD patients [8].…”

Section: Discussioncontrasting

confidence: 48%

Uncoupling protein‐3 content is decreased in peripheral skeletal muscle of patients with COPD

Gosker

Schrauwen²,

Hesselink³

et al. 2003

Eur Respir J

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Mechanical efficiency is reduced in patients with chronic obstructive pulmonary disease (COPD). Furthermore, altered fibre-type distribution and metabolic profile has been observed in peripheral skeletal muscle of COPD patients. Since skeletal muscular uncoupling protein-3 (UCP3) has been implicated in the regulation of energy metabolism, the aim of this study was to assess UCP3 in peripheral skeletal muscle of COPD patients and healthy controls.A total of 16 COPD patients and 11 healthy age-matched control subjects were studied. Mechanical efficiency was measured by means of cycle ergometry. Biopsies were taken from the vastus lateralis, and UCP3 and cytochrome c (as a marker for mitochondrial content) levels were assessed by Western blotting. Muscle fibre types and metabolic profile were examined histochemically. UCP3 levels were markedly decreased in COPD compared to controls. In COPD patients, there was a positive correlation between UCP3 content and the forced expiratory volume in one second. UCP3 content was not related to mechanical efficiency, or other muscular data such as fibre types, markers of oxidative/glycolytic energy metabolism or cytochrome c.The authors of this study conclude that uncoupling protein-3 content is decreased in peripheral skeletal muscle of patients with chronic obstructive pulmonary disease and is related to disease severity, but not to mechanical efficiency. The low uncoupling protein-3 content is independent of the loss of oxidative capacity observed in these patients. Total daily energy expenditure (EE) is often elevated in chronic obstructive pulmonary disease (COPD) patients [1], suggesting that these patients are characterised by hypermetabolism. Total daily EE consists of the resting EE, dietinduced thermogenesis and energy spent during daily activities. Although diet-induced thermogenesis is normal in COPD and can therefore be ignored [2], elevated resting EE has been observed in some COPD patients [3,4]. However, it has been shown that total daily EE is elevated independent of resting EE [5], suggesting that the elevated total EE in COPD is related to daily activities. Due to the physical disabilities of patients with COPD, it must be assumed that these patients perform less physical activities compared to healthy subjects. Therefore, the elevated total daily EE is most likely explained by an elevated energy cost for physical activity. Indeed, mechanical efficiency, measured by means of submaximal exercise testing, is decreased in these patients [6].The reason for the decreased mechanical efficiency in COPD patients is not known. SALA et al. [7] showed that for any specific workload, oxygen uptake of the leg is higher compared to healthy control subjects, suggesting that intrinsic muscular abnormalities are involved. Intrinsic abnormalities have indeed been found in peripheral skeletal muscles in COPD, of which, from a metabolic point of view, the most obvious are a reduction in the fibre type I proportion and a decreased oxidative capacity [8]. These findings ...

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Section: Discussioncontrasting

confidence: 48%

Uncoupling protein‐3 content is decreased in peripheral skeletal muscle of patients with COPD

Gosker

Schrauwen²,

Hesselink³

et al. 2003

Eur Respir J

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“…1 There are indications that the blunted b-adrenergically mediated lipolysis in obesity may be related to an impaired function or a reduced number of adipocyte beta-2 (b 2 ) adrenoceptors. 5,6 b 2 -Adrenoceptors are stimulatory G-protein-coupled (G s ) receptors. The b 2 -adrenoceptor (ADRB2) gene is encoded by an intronless gene on chromosome 5q31-q32.…”

Section: Introductionmentioning

confidence: 99%

Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation

et al. 2006

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Background and aims: Obesity is associated with a blunted b-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the b 2 -adrenoceptor gene (ADRB2) and exon 10 of the G protein b 3 -subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation. Design and methods: Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m 2 ) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective b-agonist isoprenaline (ISO). Results: In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation. Conclusion: These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo b-adrenoceptor-mediated lipolysis and fat oxidation during b-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.

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“…In addition, reduced skeletal muscle activity of 3-hydroxyacyl CoA dehydrogenase, which regulates the b-oxidation of fatty acids, has consistently been shown in normalweight COPD patients [8]. Finally, an impaired badrenoceptor-mediated increase in plasma levels of nonesterified fatty acids was reported in sarcopaenic COPD patients [9], which is suggestive of reduced lipolysis. However, whole-body AFFILIATIONS *Dept of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Hospital, Maastricht, and lipolytic rate and differences in lipid kinetics between sarcopaenic and underweight COPD patients have not been studied until now.…”

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confidence: 91%

Whole-body resting and exercise-induced lipolysis in sarcopaenic patients with COPD

Franssen¹,

Sauerwein²,

Rutten³

et al. 2008

European Respiratory Journal

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Impaired b-adrenoceptor-mediated lipolysis has been reported in sarcopaenic chronic obstructive pulmonary disease (COPD) patients. This could play a role in the shift in body composition towards decreased fat-free mass (FFM) and relative maintenance of fat mass (FM). Lipolysis could be affected by chronic treatment with b 2 -agonists or disease-related factors. Therefore, whole-body resting and exercise-induced lipolysis were investigated in sarcopaenic COPD patients with moderate disease severity.Seven sarcopaenic COPD patients (mean¡SEM forced expiratory volume in one second (FEV1) 53¡5% of the predicted value; body mass index (BMI) 27.5¡0.9 kg?m -2 ) and seven controls matched for age, sex and BMI were studied. In addition, six underweight COPD patients (FEV1 51¡5% pred; BMI 20.6¡0.7 kg?m -2) matched for disease severity were recruited. Lipolysis and plasma levels of catecholamines were assessed during infusion of [ 2 H 5 ]glycerol at rest and during submaximal cycling exercise.The proportional FM was comparable between sarcopaenic patients and controls, whereas the FFM index was significantly reduced in patients. At rest, the rate of appearance (Ra) ) was also comparable. End-of-exercise lipolytic rates did not differ significantly between groups. Glycerol Ra was not related to FM. Resting adrenalin levels were significantly increased in underweight COPD patients and were related to resting lipolysis.Sarcopaenia in chronic obstructive pulmonary disease patients with moderate disease severity is not characterised by an abnormal lipolytic rate. Altered regulation of muscle protein turnover seems to be the trigger in the body compositional shift observed in these patients.

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β-Adrenoceptor-mediated thermogenesis and lipolysis in patients with chronic obstructive pulmonary disease

Cited by 20 publications

References 40 publications

Uncoupling protein‐3 content is decreased in peripheral skeletal muscle of patients with COPD

Uncoupling protein‐3 content is decreased in peripheral skeletal muscle of patients with COPD

Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation

Whole-body resting and exercise-induced lipolysis in sarcopaenic patients with COPD

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