Andreas M. Niess

High Cardiorespiratory Fitness is an independent Predictor of the Reduction in Liver Fat during a Lifestyle Intervention in Non-Alcoholic Fatty Liver Disease

Objective: Lifestyle intervention with diet modification and increase in physical activity is effective for reducing hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). However, for a similar weight loss, there is a large variability in the change in liver fat. We hypothesised that cardiorespiratory fitness may predict the response to the intervention. Design: Longitudinal study with increase in physical activity and diet modification. Setting: University teaching hospital. Patients: 50 adults with NAFLD and 120 controls at risk for metabolic diseases. Main outcome measures: Total-, subcutaneous abdominal- and visceral adipose tissue by magnetic resonance tomography, liver fat by 1HMR spectroscopy and cardiorespiratory fitness (VO2,max) by a maximal cycle exercise test at baseline and after 9 months of follow-up. Results: In all subjects total-, subcutaneous abdominal- and visceral adipose tissue decreased and fitness increased (all p<0.0001) during the intervention. The most pronounced changes were found for liver fat (−31%, p<0.0001). Among the parameters predicting the change in liver fat, fitness at baseline emerged as the strongest factor, independently of total- and visceral adipose tissue as well as exercise intensity (p = 0.005). In the group of subjects with NAFLD at baseline, a resolution of NAFLD was found in 20 individuals. For 1 standard deviation increase in VO2,max at baseline the odds ratio for resolution of NAFLD was 2.79 (95% confidence interval, 1.43–6.33). Conclusions: Cardiorespiratory fitness, independently of total adiposity, body fat distribution and exercise intensity, determines liver fat content in humans, suggesting that fitness and liver fat are causally related to each other. Moreover, measurement of fitness at baseline predicts the effectiveness of a lifestyle intervention in reducing hepatic steatosis in patients with NAFLD.

Predicting competition performance in long-distance running by means of a treadmill test.

PURPOSE The purpose of this study was to examine the power of 16 parameters beside the individual anaerobic threshold (IAT) in predicting performance in various competition distances. METHODS This study examined 427 competitive runners to test the prediction probability of the IAT and other parameters for various running distances. All runners (339 men, 88 women; ages, 32.5 +/- 10.14 yr; training, 7.1 +/- 5.53 yr; training distance, 77.9 +/- 35.63 km.wk-1) performed an increment test on the treadmill (starting speed, 6 or 8 km.h-1; increments, 2 km.h-1; increment duration, 3 min to exhaustion). The heart rate (HR) and the lactate concentrations in hemolyzed whole blood were measured at rest and at the end of each exercise level. The IAT was defined as the running speed at a net increase in lactate concentration 1.5 mmol.L-1 above the lactate concentration at LT. RESULTS Significant correlations (r = 0.88-0.93) with the mean competition speed were found for the competition distances and could be increased using stepwise multiple regression (r = 0.953-0.968) with a set of additional parameters from the training history, anthropometric data, or the performance diagnostics. CONCLUSIONS The running speed at a defined net lactate increase thus produces an increasing prediction accuracy with increasing distance. A parallel curve of the identity straight lines with the straight lines of regression indicates the independence of at least a second independent performance determining factor.

HSP expression in human leukocytes is modulated by endurance exercise.

PURPOSE Temperature increase, oxidative stress, and inflammatory reactions after endurance exercise were expected to stimulate the synthesis of heat shock proteins (HSP) in peripheral blood leukocytes. Furthermore, it was of interest whether regular endurance training influences HSP expression. METHODS The expression of HSP27, HSP60, HSP70, constitutive HSC70, and HSP90 in the cytoplasma and surface of lymphocytes, monocytes, and granulocytes of 12 trained athletes was analyzed by flow cytometry before and after (0, 3, and 24 h) a half marathon. Twelve untrained persons at rest were included as control. RESULTS After the race, there was a significantly greater percentage of leukocytes expressing cytoplasmic HSP27, HSP60, and HSP70 (P < 0.01), whereas HSC70 and HSP90 remained unchanged. The fluorescence intensity increased significantly in monocytes for HSP27 (0 and 3 h) and HSP70 (0, 3, and 24 h) and in granulocytes, only 24 h postexercise for HSP70. The percent values of trained athletes at rest were significantly lower compared with untrained persons (P < 0,01). CONCLUSIONS Strenuous exercise increased HSP expression in blood immediately after the run, indicating a protective function of HSP in leukocytes of athletes to maintain function after heavy exercise. The downregulation of HSP-positive cells in trained athletes at rest seems to be a result of adaptation mechanisms to regular endurance training.

Exercise-induced normalization of decreased BDNF serum concentration in elderly women with remitted major depression

Major depression (MD) has been associated with decreased brain-derived neurotrophic factor (BDNF) serum levels, while antidepressant drugs were found to increase these decreased BDNF levels. We investigated if this is also caused by a single exercise session in elderly women with remitted MD. In our study 35 elderly women with a (partially) remitted depressive episode of unipolar depression according to DSM-IV criteria within the last year and 20 age-matched healthy female controls were included. Depression severity was assessed by HAMD. Serum levels of BDNF were measured by ELISA. Blood samples were taken during the rest period before beginning the exercise including spiroergometry, at the end of the exercise and after a 30-min recovery period. At baseline MD patients showed significantly decreased BDNF serum levels compared to healthy female controls. After a single 30-min exercise period, we found a significant increase of BDNF serum levels in MD patients towards values comparable with the baseline levels of the healthy controls, followed by a significant decrease after 30 min rest, while the healthy controls showed only a mild but non-significant increase. In conclusion, a single exercise session leads to a significant up-regulation and transient normalization of BDNF serum levels in elderly women with remitted MD. This mechanism may contribute to the beneficial therapeutic and relapse-preventing effects of physical activity on MD.

Lifestyle intervention in individuals with normal versus impaired glucose tolerance

Background  Lifestyle intervention is effective in the prevention of type 2 diabetes in individuals with impaired glucose tolerance (IGT). It is currently unknown whether it has beneficial effects on metabolism to a similar extent, in individuals with normal glucose tolerance (NGT) compared to individuals with IGT.

Expression of the antioxidant stress protein heme oxygenase-1 (HO-1) in human leukocytes: Acute and adaptational responses to endurance exercise

Inducible heme oxygenase (HO-1) is an antioxidant stress protein, that is mainly induced by reactive oxygen species (ROS), cytokines and hyperthermia. By using flow cytometry the present investigation demonstrated a rise in the cytoplasmic expression of HO-1 in lympho- (L), mono- (M) and granulocytes (G) of 9 endurance-trained male subjects after a half marathon run. The expression was more pronounced in M (median: 98.3% HO-1 positive cells/4.31 mfc) and G (94.8%/1.93 mfc) than in L (80.1%/1.51 mfc) when measured 3 h post-exercise. Additionally the exercise protocol caused a rise in the plasma levels of myeloperoxidase, TNF alpha and interleukin-8 (IL-8), indicating an inflammatory response. We could detect a correlation between IL-8 and HO-1, directly after exercise, that was apparent in G (r = 0.67, p < .05) and L (r = 0.80, p < .05), but did not reach significance in M (r = 0.65, p = 0.06). An additional detection of HO-1 at rest in 12 untrained subjects showed a higher baseline expression of HO-1 compared to the athletes. The regulatory pathways leading to an increased expression of HO-1 after endurance exercise are not completely clear, but a causal involvement of a cytokine-mediated generation of ROS must be discussed. We supposed that the down-regulation of the baseline expression of HO-1 in athletes reflects an adaptional mechanism to regular exercise training.

Medium Chain Acylcarnitines Dominate the Metabolite Pattern in Humans under Moderate Intensity Exercise and Support Lipid Oxidation

Background Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise. Methodology and Principal Findings First, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT-) metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under these conditions medium and long chain acylcarnitines were found to be the most discriminant plasma biomarkers of moderately intense exercise. Immediately after a 60 min (at 93% VIAT) or a 120 min run (at 70% VIAT) a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial β-oxidation was verified in skeletal muscle cell culture experiments by probing 13C-palmitate metabolism. Further investigations in primary human myotubes and mouse muscle tissue revealed that octanoyl-, decanoyl-, and dodecanoyl-carnitine were able to support the oxidation of palmitate, proving more effective than L-carnitine. Conclusions Medium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.

Changes of HSP72-expression in leukocytes are associated with adaptation to exercise under conditions of high environmental temperature

Overexpression of the heat shock protein HSP72 providesthermotolerance. We asked if two consecutive endurance runs 1 weekapart (CR1, CR2) and additional environmental heat stress affectHSP72‐expression in leukocytes of nonheat‐acclimated enduranceathletes. Twelve subjects were allocated randomly into two groups. Group HH completed both runs at 28°C ambient temperature, and groupNH performed CR1 at 18°C and CR2 at 28°C. HSP72‐expression wasdetermined by flow cytometry and RT‐PCR before and 0, 24, and 48 hafter exercise. Additionally, post‐exercise cells were exposed toin vitro heat shock (HS; 2 h, 42°C). The prolonged, high HSP72 protein level after CR1 in HH compared with NH may reflectthermotolerance induced by endurance exercise at high ambienttemperature. Adaptation of cardiocirculatory/thermoregulatory capacityafter CR2 in HH went along with a more rapid down‐regulation of HSP72compared with CR1. HSP72 mRNA demonstrated temperature‐related changesafter exercise. The reduced HS response in vitro after CR2may represent exercise‐related adaptation mechanisms. HSP72concentrations in leukocytes may indicate previous exercise‐ andtemperature‐related stress conditions and adaptation in immunocompetentcells.

Differential regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) splice variants based on alternative initiation of transcription.

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a key-regulator of transport, cell volume and cell survival. SGK1 transcription is under genomic control of a wide variety of hormones and cell stressors. Little is known, however, about sequence variation in SGK1 transcripts. Thus, we took an in silico approach to determine sequence variations in the N-terminal region of SGK1, which is considered particularly important for subcellular SGK1 localization. Expressed Sequence Tag analysis revealed two novel phylogenetically highly conserved SGK1 mRNAs with different promoter sites based on alternative initiation of transcription at -2981, -850 upstream of the transcription initiation site (+1) of the reference mRNA. RT-PCR in various human cell lines and tissues confirmed the expression of the 3 alternative splice variants, which differed exclusively in their first exons. The two novel variants were devoid of the localization and degradation signal with otherwise unchanged and intact open reading frames. Spatial distribution of transcription factor binding sites among the three promoter sites indicated common responsiveness to glucocorticoids but different responsiveness to hypoxia and cellular differentiation. Differential expression under those conditions was confirmed for all variants in cultured myoblasts and myotubes. p53 and ETF-1 binding sites were overrepresented at the promoter site of the reference sequence variant SGK1(+1). Transcript levels were 4.1-fold [SGK1(+1)] and 3.1-fold [SGK1(-850)] higher in renal clear cell carcinoma than in remote tissue. The transcript levels were 42-fold [SGK1(+1)], 26-fold [SGK1(-850)] and 17-fold [SGK1(-2981)] higher in highly malignant human glioma cells than in non-neoplastic brain tissue. SGK1 transcript levels were differentially increased by differentiation or hypoxia (treatment with CoCl2). In conclusion, the present observations disclose the transcription of three distinct SGK1 splice variants, which are all markedly upregulated in tumor tissue but differentially upregulated following differentiation or hypoxia.

Evaluation of stress responses to interval training at low and moderate altitudes

PURPOSE The purpose of the present field study was to explore whether extensive interval training (IT) performed with a similar behavior of blood lactate (LA) at an altitude of 1800 m (ALT) and near sea level (SL) goes along with a comparable hormonal, metabolic, and acute phase response in highly trained endurance athletes. METHODS Twelve distance runners (VO2 64.6 +/- 6.9 mL.kg(-1) ) performed IT (10 x 1000 m, 2-min rest) at SL with a running velocity (V) corresponding to 112% of the individual anaerobic threshold (IAT). After an acclimatization period of 7 d, IT was repeated with a lower V (107% IAT) at ALT. Blood samples were drawn at rest, 0, 0.3, 3, and 24 h after IT. LA during IT was similar at SL and ALT (5.4 +/- 1.3/5.3 +/- 1.2 mmol.L(-1)), whereas HR tended to be higher at SL. RESULTS Postexercise rises in plasma noradrenaline (NA), NA sulfate, adrenaline, glucose, interleukin-6 (IL-6), and neutrophils were significantly more pronounced at ALT. The increase of cortisol and human growth hormone showed an insignificant trend toward higher values at ALT. A slight but significant increase of plasma erythropoietin was only apparent after IT at ALT. No differences between either condition were observed for exercise-related changes in free fatty acids, IL-8, lympho-, or monocyte counts. CONCLUSIONS In spite of a matched accumulation pattern of LA between ALT and N, stress responses, such as sympathetic activation and hepatic glucose release, still appear to be greater at ALT. This additional impact of moderate ALT on the stress response to IT should be taken into account if repeated training sessions are performed within a short period of time.