Body Resting Energy Expenditure Research Articles

Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) prevent vascular events and are widely prescribed, particularly in persons with type 2 diabetes. However, intolerability because of myopathic symptoms often limits their use. We investigated the effects of simvastatin on parameters of mitochondrial function and muscle gene expression in 11 subjects with type 2 diabetes, none of whom had statin intolerance. After withdrawal of statins for 2 months, we obtained blood samples, performed vastus lateralis muscle biopsies, and assessed whole body resting energy expenditure (REE). We then reinitiated therapy using simvastatin, 20 mg/d, for 1 month before repeating these studies. As expected, simvastatin lowered low-density lipoprotein, but did not induce myalgias or significant increases in serum creatine kinase. However, we found subtle but significant reductions in muscle citrate synthase activity and REE. In addition, quantitative polymerase chain reaction and gene set enrichment analysis of muscle samples revealed significantly repressed gene sets involved in mitochondrial function and induced gene sets involved in remodeling of the extracellular matrix. Furthermore, the effects of simvastatin on muscle gene sets showed some similarities to previously described changes that occur in Duchenne muscular dystrophy, polymyositis, and dermatomyositis. Although statins inhibit an early step in coenzyme Q (CoQ) biosynthesis, we observed no differences in CoQ content within skeletal muscle mitochondria, muscle tissue, or circulating platelets. In summary, we report subtle changes in whole body energetics, mitochondrial citrate synthase activity, and microarray data consistent with subclinical myopathy. Although the benefits of statin therapy are clear, further understanding of muscular perturbations should help guide safety and tolerability.

Advances in the understanding of specific metabolic rates of major organs and tissues in humans

To present recent evidence on organ and tissue metabolic rates in humans to explain the variance in resting energy expenditure (REE). In humans, present knowledge on specific metabolic activities (i.e. ki-values) refers to seven organs and tissues - brain, heart, liver, kidneys, skeletal muscle, adipose tissue and residual mass - with ki-values of 240, 440, 200, 440, 13, 4.5 and 12 kcal/kg/day, provided by Elia in 1992. Detailed body composition data, as derived from whole body MRI together with measurements of whole body REE, were used to validate ki-values in nonobese, healthy and middle-aged adults. There is no sex difference, but minor, that is 2 and 3% deviations are found for age above 55 years and obesity, respectively. By contrast, in adolescents, differences of about 100 kcal/day or 7.3% of measured REE were observed. There is first evidence for changes in ki-values with either weight loss or weight regain after weight loss. Altogether these data suggest that in adolescence and at age above 55 years, in the obese and with weight change, organ and tissue masses differ in cellularity and/or their specific metabolic rates. Presently, direct assessment of specific organ and tissue metabolic rates in humans by either NMR spectroscopy or PET, together with detailed body composition analysis, has not been performed systematically. We need to become more skilled in methods and models used for detailed body composition analysis together with detailed assessment of energy expenditure in humans.

Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure

ObjectiveTrimetazidine may have beneficial effects on left ventricular (LV) function in patients with systolic heart failure. The authors assessed whether long-term addition of trimetazidine to conventional treatment could improve, along...

Genes and biochemical pathways in human skeletal muscle affecting resting energy expenditure and fuel partitioning

Genes influencing resting energy expenditure (REE) and respiratory quotient (RQ) represent candidate genes for obesity and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. We aim to explore the molecular basis for individual variation in REE and fuel partitioning as reflected by RQ. We performed microarray studies in human vastus lateralis muscle biopsies from 40 healthy subjects with measured REE and RQ values. We identified 2,392 and 1,115 genes significantly correlated with REE and RQ, respectively. Genes correlated with REE and RQ encompass a broad array of functions, including carbohydrate and lipid metabolism, gene expression, mitochondrial processes, and membrane transport. Microarray pathway analysis revealed that REE was positively correlated with upregulation of G protein-coupled receptor signaling (meet criteria/total genes: 65 of 283) involved in autonomic nervous system functions, including those receptors mediating adrenergic, dopamine, γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total genes: 46 of 176). Reduced REE was associated with an increase in genes participating in ubiquitin-proteasome-dependent proteolytic pathways (58 of 232). Serine-type peptidase activity (9 of 76) was positively correlated with RQ, while genes involved in the protein phosphatase type 2A complex (4 of 9), mitochondrial function and cellular respiration (38 of 315), and unfolded protein binding (19 of 97) were associated with reduced RQ values and a preference for lipid fuel metabolism. Individual variations in whole body REE and RQ are regulated by differential expressions of specific genes and pathways intrinsic to skeletal muscle.

Metabolically active portion of fat-free mass: a cellular body composition level modeling analysis.

The proportion of fat-free mass (FFM) as body cell mass (BCM) is highly related to whole body resting energy expenditure. However, the magnitude of BCM/FFM may have been underestimated in previous studies. This is because Moore's equation [BCM (kg) = 0.00833 x total body potassium (in mmol)], which was used to predict BCM, underestimates BCM by approximately 11%. The aims of the present study were to develop a theoretical BCM/FFM model at the cellular level and to explore the influences of sex, age, and adiposity on the BCM/FFM. Subjects were 112 adults who had the following measurements: total body water by (2)H(2)O or (3)H(2)O dilution; extracellular water by NaBr dilution; total body nitrogen by in vivo neutron activation analysis; and bone mineral by dual-energy X-ray absorptiometry. FFM was calculated using a multicomponent model and BCM as the difference between FFM and the sum of extracellular fluid and solids. The developed theoretical model revealed that the proportion of BCM to FFM is mainly determined by water distribution (i.e., E/I, the ratio of extracellular to intracellular water). A significant correlation (r = 0.90, P < 0.001) was present between measured and model-predicted BCM/FFM for all subjects pooled. Measured BCM/FFM [mean (SD)] was 0.584 +/- 0.041 and 0.529 +/- 0.041 for adult men and women (P < 0.001), respectively. A multiple linear regression model showed that there are independent significant associations of sex, age, and fat mass with BCM/FFM.

In vivo rabbit hindquarter model for assessment of regional burn hypermetabolism.

Severe burn injury evokes hypermetabolism and muscle wasting, despite nominally adequate nutrition. Although there is much information on whole organism and isolated tissue metabolism after burn injury, data examining regional burn hypermetabolism in vivo are lacking. Using surgically implanted (general anesthesia) regional vascular catheters and primed constant infusion of l-[1-(13)C]phenylalanine tracer, we have determined in vivo burn-induced alterations in rabbit hindquarter protein and energy metabolism. Burn injury evokes increased whole body resting energy expenditure and phenylalanine turnover, accompanied by significantly increased hindquarter proteolysis, creating a negative protein balance in burned rabbit hindquarter. Hindquarter oxygen consumption showed an increase after burn injury, but it did not reach statistical significance. Burn-induced changes in hindquarter protein turnover account for approximately one-third of the whole animal hypermetabolism. This model offers a system for regional manipulation of postburn hypermetabolism.

Smaller organ tissue mass in the elderly fails to explain lower resting metabolic rate.

We previously reported our in vivo prediction of whole body resting energy expenditure (REE) using magnetic resonance imaging and echocardiography-derived organ volumes combined with published organ tissue metabolic rates. The models, developed in young healthy persons from predicted and measured variables, were highly correlated (e.g., calculated vs. measured REE, r = 0.92, p < 0.001), with no significant differences (p = NS) between them. This study employed the same approach to determine whether possible age-related decreases in organ tissue mass may account for the lower REE commonly reported in elderly persons. Measurements of REE (REEm) were acquired by indirect calorimetry. Calculated REE (REEc) models were developed from measured tissues and organs, and energy flux rates were assigned for each of the seven tissue/organ components, as reported by Elia. Older men (n = 6) and women (n = 7) had significantly lower REEm compared to REEc (p = 0.001). The magnitude of the differences were 13% and 9.5%, respectively, for men and women. These preliminary data suggest that factors other than organ atrophy may contribute to the lower metabolic rate of older persons. Further studies are required to investigate whether there is a reduction in the oxidative capacity of individual organs and tissues.

Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass.

Investigators have expressed interest in the associations between resting energy expenditure (REE) and body mass for over a century. Traditionally, descriptive models using regression analysis are applied, linking REE with metabolically active compartments such as body cell mass (BCM) and fat-free body mass (FFM). Recently developed whole body magnetic resonance imaging (MRI) and echocardiography methods now allow estimation of all major organs and tissue volumes in vivo. Because measured values are available for REE, BCM, and FFM content of individual organs and tissues, it should now be possible to develop energy expenditure-body composition estimation models based on MRI-measured organ-tissue volumes. Specifically, the present investigation tested the hypothesis that in vivo estimation of whole body REE, BCM, and FFM is possible using MRI- and echocardiography-derived organ volumes combined with previously reported organ-tissue metabolic rates and chemical composition. Thirteen subjects (5 females, 8 males) had REE, BCM, and FFM measured by indirect calorimetry, whole body 40K counting, and dual-energy X-ray absorptiometry, respectively. Models developed from estimated and measured variables were highly correlated, with no significant differences between those estimated and measured [e.g., calculated vs. measured REE: r = 0.92, P < 0. 001; (mean +/- SD) 6,962 +/- 1,455 and 7,045 +/- 1,450 kJ/day, respectively (P = not significant)]. Strong associations were observed between REE, individual or combined organ weights, BCM, and FFM that provide new insights into earlier observed metabolic phenomona. The present approach, the first to establish an energy expenditure-body composition link with a mechanistic model in vivo, has the potential to greatly expand our knowledge of energy expenditure-body size relationships in humans.

Glucose‐induced thermogenesis in patients with small cell lung carcinoma. Before and after inhibition of tumour growth by chemotherapy

Seven weight-losing patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g before and at least 3 weeks after the end of chemotherapy to examine the effect of glucose on whole body and skeletal muscle thermogenesis before and after reduction of tumour. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous-occlusion strain-gauge plethysmography. The uptake of oxygen in skeletal muscle was calculated as the product of the forearm blood flow and the difference in a-v oxygen concentration. Whole body resting energy expenditure (REE) did not increase, it was 4.4 +/- 0.3 kJ min-1 (mean +/- SE) before chemotherapy and 4.4 +/- 0.2 kJ min-1 after chemotherapy. The glucose-induced thermogenesis in the 180 min following the glucose load was 93.6 +/- 9.9 kJ 180 min-1 before chemotherapy. This is significantly increased compared to that found in a healthy control group (74.7 +/- 4.8 kJ 180 min-1, P < 0.02). The glucose-induced thermogenesis was significantly reduced to 47.7 +/- 10.2 kJ 180 min-1 (P < 0.05) after chemotherapy. The oxygen uptake in resting skeletal muscles was 6.9 +/- 0.3 mumol 100 g-1 min-1 before chemotherapy and 7.0 +/- 0.7 mumol 100 g-1 min-1 after chemotherapy. This did not increase during the first 90 min following the glucose load in either investigations. In the period 90-180 min following the glucose load, the oxygen uptake was significantly increased before chemotherapy as compared to after chemotherapy, which suggests that the reduced whole body thermogenesis after chemotherapy in part was due to reduced skeletal muscle thermogenesis.

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue.

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.