Elisabet Børsheim

Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneutral conditions and after prolonged (5–8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.

Effect of Exercise Intensity, Duration and Mode on Post-Exercise Oxygen Consumption

In the recovery period after exercise there is an increase in oxygen uptake termed the ‘excess post-exercise oxygen consumption’ (EPOC), consisting of a rapid and a prolonged component. While some studies have shown that EPOC may last for several hours after exercise, others have concluded that EPOC is transient and minimal. The conflicting results may be resolved if differences in exercise intensity and duration are considered, since this may affect the metabolic processes underlying EPOC. Accordingly, the absence of a sustained EPOC after exercise seems to be a consistent finding in studies with low exercise intensity and/or duration. The magnitude of EPOC after aerobic exercise clearly depends on both the duration and intensity of exercise. A curvilinear relationship between the magnitude of EPOC and the intensity of the exercise bout has been found, whereas the relationship between exercise duration and EPOC magnitude appears to be more linear, especially at higher intensities.Differences in exercise mode may potentially contribute to the discrepant findings of EPOC magnitude and duration. Studies with sufficient exercise challenges are needed to determine whether various aerobic exercise modes affect EPOC differently. The relationships between the intensity and duration of resistance exercise and the magnitude and duration of EPOC have not been determined, but a more prolonged and substantial EPOC has been found after hardversus moderate-resistance exercise. Thus, the intensity of resistance exercise seems to be of importance for EPOC.Lastly, training status and sex may also potentially influence EPOC magnitude, but this may be problematic to determine. Still, it appears that trained individuals have a more rapid return of post-exercise metabolism to resting levels after exercising at either the same relative or absolute work rate; however, studies after more strenuous exercise bouts are needed. It is not determined if there is a sex effect on EPOC.Finally, while some of the mechanisms underlying the more rapid EPOC are well known (replenishment of oxygen stores, adenosine triphosphate/creatine phosphate resynthesis, lactate removal, and increased body temperature, circulation and ventilation), less is known about the mechanisms underlying the prolonged EPOC component. A sustained increased circulation, ventilation and body temperature may contribute, but the cost of this is low. An increased rate of triglyceride/fatty acid cycling and a shift from carbohydrate to fat as substrate source are of importance for the prolonged EPOC component after exhaustive aerobic exercise. Little is known about the mechanisms underlying EPOC after resistance exercise.

Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress

Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT was determined by the presence of multilocular adipocytes, uncoupling protein 1 (UCP1), and increased mitochondrial density and respiratory capacity. Multilocular UCP1-positive adipocytes were found in sWAT samples from burn patients. UCP1 mRNA, mitochondrial density, and leak respiratory capacity in sWAT increased after burn trauma. Our data demonstrate that human sWAT can transform from an energy-storing to an energy-dissipating tissue, which opens new research avenues in our quest to prevent and treat obesity and its metabolic complications.

Health effects of protein intake in healthy adults: a systematic literature review

The purpose of this systematic review is to assess the evidence behind the dietary requirement of protein and to assess the health effects of varying protein intake in healthy adults. The literature search covered the years 2000–2011. Prospective cohort, case-control, and intervention studies were included. Out of a total of 5,718 abstracts, 412 full papers were identified as potentially relevant, and after careful scrutiny, 64 papers were quality graded as A (highest), B, or C. The grade of evidence was classified as convincing, probable, suggestive or inconclusive. The evidence is assessed as: probable for an estimated average requirement of 0.66 g good-quality protein/kg body weight (BW)/day based on nitrogen balance studies, suggestive for a relationship between increased all-cause mortality risk and long-term low-carbohydrate–high-protein (LCHP) diets; but inconclusive for a relationship between all-cause mortality risk and protein intake per se; suggestive for an inverse relationship between cardiovascular mortality and vegetable protein intake; inconclusive for relationships between cancer mortality and cancer diseases, respectively, and protein intake; inconclusive for a relationship between cardiovascular diseases and total protein intake; suggestive for an inverse relationship between blood pressure (BP) and vegetable protein; probable to convincing for an inverse relationship between soya protein intake and LDL cholesterol; inconclusive for a relationship between protein intake and bone health, energy intake, BW control, body composition, renal function, and risk of kidney stones, respectively; suggestive for a relationship between increased risk of type 2 diabetes (T2D) and long-term LCHP-high-fat diets; inconclusive for impact of physical training on protein requirement; and suggestive for effect of physical training on whole-body protein retention. In conclusion, the evidence is assessed as probable regarding the estimated requirement based on nitrogen balance studies, and suggestive to inconclusive for protein intake and mortality and morbidity. Vegetable protein intake was associated with decreased risk in many studies. Potentially adverse effects of a protein intake exceeding 20–23 E% remain to be investigated.

Short-term effects of exercise on plasma very low density lipoproteins (VLDL) and fatty acids.

PURPOSE In the fasted state the lipid fuels for muscle metabolism are free fatty acids (FFA) released either from intramuscular triglycerides (TG), plasma albumin, or TG in circulating very low density lipoproteins (VLDL). The purposes of this study were to determine the influence of acute exercise of moderate intensity on 1) plasma total concentration of TG and VLDL components, 2) the plasma concentration and distribution of individual albumin-bound long-chain FFA, and 3) lipid peroxidation as measured by thiobarbituric acid reactive substances (TBARS). METHODS Eight healthy male subjects each participated in one exercise (EX) and one rest (RE) experiment. In EX the subjects exercised for 90 min at 58+/-5% (mean +/- SD) of maximal O2 uptake on a cycle ergometer followed by 4.5 h bedrest. RE followed the same protocol, but without exercise. RESULTS In EX there was no immediate change in VLDL concentration during the exercise. After exercise there was a decrease in VLDL, VLDL-TG, -cholesterol, -protein and -phospholipids compared with those after RE. There was no change in percentage composition of VLDL as result of exercise. Total plasma FFA concentration increased appreciably during exercise and remained elevated for several hours postexercise. There was no correlation between the change in FFA concentration and VLDL-TG. There was a significant positive correlation between the exercise-related increments in the various long-chain FFA, but the effect varied so that the relative abundance of oleic acid increased and that of stearic and arachidonic acid decreased during exercise. Plasma TBARS concentration increased during the day in both experiments. CONCLUSION The results indicate that there is a delay in the effect of an exercise bout on plasma VLDL and confirm that exercise affects various FFA in plasma differentially.

Population Volume Kinetics Predicts Retention of 0.9% Saline Infused in Awake and Isoflurane-anesthetized Volunteers

Background:In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. Methods:Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. Results:Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration–derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. Conclusion:Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.

Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training

Although antioxidant supplements are generally believed to give health benefits, recent experiments show that they may adversely affect adaptations to endurance exercise. This study is the first to investigate the effects of high dosages of vitamins C and E on the cellular and physiological adaptations to strength training in humans. Here we report that vitamin C and E supplementation interfered with exercise‐induced signalling in muscle cells after a session of strength training, by reducing the phosphorylation of p70S6 kinase and mitogen‐activated protein kinases p38 and ERK1/2. The vitamin C and E supplement did not significantly blunt muscle hypertrophy during 10 weeks of training; however, some measurements of muscle strength revealed lower increases in the supplemented group than the placebo group. Even though the cellular events are not clearly reflected in physiological and performance measurements, this study implies that redox signalling is important for inducing skeletal muscle adaptations to strength training and that vitamin C and E supplements in high dosages should be avoided by healthy, young individuals engaged in strength training.

The Role of MicroRNAs in Diabetic Complications—Special Emphasis on Wound Healing

Overweight and obesity are major problems in today’s society, driving the prevalence of diabetes and its related complications. It is important to understand the molecular mechanisms underlying the chronic complications in diabetes in order to develop better therapeutic approaches for these conditions. Some of the most important complications include macrovascular abnormalities, e.g., heart disease and atherosclerosis, and microvascular abnormalities, e.g., retinopathy, nephropathy and neuropathy, in particular diabetic foot ulceration. The highly conserved endogenous small non-coding RNA molecules, the micro RNAs (miRNAs) have in recent years been found to be involved in a number of biological processes, including the pathogenesis of disease. Their main function is to regulate post-transcriptional gene expression by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation, suppression of translation or even gene activation. These molecules are promising therapeutic targets and demonstrate great potential as diagnostic biomarkers for disease. This review aims to describe the most recent findings regarding the important roles of miRNAs in diabetes and its complications, with special attention given to the different phases of diabetic wound healing.

The impact of severe burns on skeletal muscle mitochondrial function

Severe burns induce a pathophysiological response that affects almost every physiological system within the body. Inflammation, hypermetabolism, muscle wasting, and insulin resistance are all hallmarks of the pathophysiological response to severe burns, with perturbations in metabolism known to persist for several years post injury. Skeletal muscle is the principal depot of lean tissue within the body and as the primary site of peripheral glucose disposal, plays an important role in metabolic regulation. Following a large burn, skeletal muscle functions as and endogenous amino acid store, providing substrates for more pressing functions, such as the synthesis of acute phase proteins and the deposition of new skin. Subsequently, burn patients become cachectic, which is associated with poor outcomes in terms of metabolic health and functional capacity. While a loss of skeletal muscle contractile proteins per se will no doubt negatively impact functional capacity, detriments in skeletal muscle quality, i.e. a loss in mitochondrial number and/or function may be quantitatively just as important. The goal of this review article is to summarise the current understanding of the impact of thermal trauma on skeletal muscle mitochondrial content and function, to offer direction for future research concerning skeletal muscle mitochondrial function in patients with severe burns, and to renew interest in the role of these organelles in metabolic dysfunction following severe burns.

Early rehabilitative exercise training in the recovery from pediatric burn.

PURPOSE The purpose of this study was to determine the effects of early outpatient exercise on muscle mass, function, and fractional synthetic rate in severely burned children. METHODS Forty-seven children with ≥40% total body surface area burn performed a 12-wk standard of care rehabilitation (SOC, n = 23) or rehabilitative exercise training (RET, n = 24) immediately after hospital discharge. Dual-energy x-ray absorptiometry was used to assess lean body mass (LBM) at discharge, posttreatment, and 12 months post-burn. Muscle function was evaluated with a Biodex Isokinetic Dynamometer, and peak aerobic fitness (V˙O2peak) was measured using a modified Bruce treadmill protocol posttreatment. Stable isotope infusion studies were performed in a subset of patients (SOC, n = 13; RET, n = 11) at discharge and posttreatment to determine mixed-muscle fractional synthetic rate. RESULTS Relative peak torque (RET, 138 ± 9 N·m·kg, vs SOC, 106 ± 9 N·m·kg) and V˙O2peak (RET, 32 ± 1 mL·kg·min, vs SOC, 28 ± 1 mL·kg·min) were greater at posttreatment with RET compared with those with SOC. In addition, RET increased whole-body (9% ± 2%) and leg (17% ± 3%) LBM compared with SOC. Furthermore, the percentage change in whole-body (18% ± 3%) and leg (31% ± 4%) LBM from discharge to 12 months post-burn was greater with RET compared to SOC. Muscle fractional synthetic rate decreased from discharge to posttreatment in both groups (6.9% ± 1.1% per day vs 3.4 ± 0.4% per day); however, no differences were observed between treatment groups at each time point. CONCLUSIONS Early outpatient exercise training implemented at hospital discharge represents an effective intervention to improve muscle mass and function after severe burn injury.