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OBJECTIVE The aim of this study was to compare three different reconstruction algorithms for the volumetry of the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) on ultra-low-dose computed tomography (CT) images. METHODS Thirty-seven male patients underwent ultra-low-dose CT at the level of the fourth lumbar vertebra (22.5 mm in z-axis). The acquisitions were reconstructed in 5-mm slices with 50% overlap using filtered back projection (FBP), hybrid iterative reconstruction (HIR), and iterative model-based reconstruction (IMR) techniques. The volume of VAT and SAT was measured using an interactive seed-growing segmentation and by thresholding (-30 to -190 HU). RESULTS The volume of SAT measured by the interactive method was smaller in FBP compared with both HIR (P = 0.0011) and IMR (P = 0.0034), and the volume of VAT was greater in IMR compared with HIR (P = 0.0253) or FBP (P = 0.0065). Using the thresholding method, IMR volumes of VAT were greater compared with HIR (P

Context Metabolic disturbances and a pro-inflammatory state associated with aging and obesity may be mitigated by physical activity or nutrition interventions. Objective The aim of this study is to assess whether physical fitness/exercise training (ET) alleviates inflammation in adipose tissue (AT), particularly in combination with omega-3 supplementation, and whether changes in AT induced by ET can contribute to an improvement of insulin sensitivity and metabolic health in the elderly. Design, Participants, Main Outcome Measures The effect of physical fitness was determined in cross-sectional comparison of physically active/physically fit (trained) and sedentary/less physically fit (untrained) older women (71 ± 4 years, n = 48); and in double-blind randomized intervention by 4 months of ET with or without omega-3 (Calanus oil) supplementation (n = 55). Physical fitness was evaluated by spiroergometry (maximum graded exercise test) and senior fitness tests. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Samples of subcutaneous AT were used to analyze mRNA gene expression, cytokine secretion, and immune cell populations. Results Trained women had lower mRNA levels of inflammation and oxidative stress markers, lower relative content of CD36+ macrophages, and higher relative content of γδT-cells in AT when compared with untrained women. Similar effects were recapitulated in response to a 4-month ET intervention. Content of CD36+ cells, γδT-cells, and mRNA expression of several inflammatory and oxidative stress markers correlated to insulin sensitivity and cardiorespiratory fitness. Conclusions In older women, physical fitness is associated with less inflammation in AT. This may contribute to beneficial metabolic outcomes achieved by ET. When combined with ET, omega-3 supplementation had no additional beneficial effects on AT inflammatory characteristics.

Klára Daďová,1 Miroslav Petr,2 James J Tufano,2 Lenka Sontáková,2 Eva Krauzová,3,4 Marek Å těpán,3 Michaela Å iklová,3 Michal Å teffl2 1Department of Adapted Physical Education and Sports Medicine, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic; 2Department of Physiology, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic; 3Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; 4Department of Internal Medicine, Královské Vinohrady University Hospital and Third Faculty of Medicine, Prague, Czech RepublicCorrespondence: Michal Å teffl, Department of Physiology, Faculty of Physical Education and Sport, Charles University, J. Martího 31, 162 52 Praha 6, Prague, Czech Republic, Tel +420 778701882, Email steffl@ftvs.cuni.czPurpose: In our study, we examined changes in short-term episodic memory and brain-derived neurotrophic factor (BDNF) in women after an exercise program alone or in combination with omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation.Patients and Methods: Fifty-five healthy elderly women (65– 80 years) were randomly split into two groups: in the first group were women attending an exercise program while taking wax esters-rich oil (Calanus) supplementation (n = 28) and in the other group were women undergoing the same exercise program while taking placebo (n = 27). The 16-week exercise program consisted of functional circuit training (twice a week) and Nordic walking lessons (once a week). Short-term episodic memory was evaluated by the Czech screening Test “Pojmenování OBrázků A jejich Vybavení” (POBAV) baseline and after the program lasting 16 weeks.Results: Our results show that short-term memory significantly improved following the exercise program, but there was no added value in using n-3 PUFA supplements. BDNF values did not differ between baseline and follow-up in either group. However, there was a statistically significant positive relationship between relative change (%) in the POBAV test and VO2peak in the placebo group (r = 0.49).Conclusion: Despite the added value of n-3 PUFA supplementation not being proven, our results may strengthen the importance of physical activity in averting age-related memory decline and dementia.Keywords: cognitive function, n-3 PUFA, physical activity, aging, circuit training, Nordic walking

Sensitive electrophoretic determination of 3-hydroxybutyrate (3HB) as an indicator of human ketogenesis is performed in fused silica capillary covalently coated by an anionic copolymer of poly(acrylamide-co-sodium-2-acrylamido-2-methylpropanesulphonate) (PAMAMPS). Baseline separation of 3HB from other components of human serum is achieved in a 20 μm capillary with an effective length of 17 cm covered by 4% PAMAMPS, which generates a cathodic EOF with a mobility of 8.30 ± 0.00 · 10

Since the 1950s, one of the goals of adipose tissue research has been to determine lipolytic and lipogenic activity as the primary metabolic pathways affecting adipocyte health and size and thus representing potential therapeutic targets for the treatment of obesity and associated diseases. Nowadays, there is a relatively large number of methods to measure the activity of these pathways and involved enzymes, but their applicability to different biological samples is variable. Here, we review the characteristics of mean lipogenic and lipolytic enzymes, their inhibitors, and available methodologies for assessing their activity, and comment on the advantages and disadvantages of these methodologies and their applicability in vivo, ex vivo, and in vitro, i.e., in cells, organs and their respective extracts, with the emphasis on adipocytes and adipose tissue.

The aim of this study was to investigate the possible beneficial effects of exercise training (ET) with omega-3/Calanus oil supplementation on cardiorespiratory and adiposity parameters in elderly women. Fifty-five women (BMI: 19–37 kg/m2 , 62–80 years old) were recruited and randomly assigned to the 4 month intervention with ET and omega-3 supplementation (Calanus oil, ET-Calanus) or ET and the placebo (sunflower oil; ET-Placebo). The body composition was determined by dual-energy X-ray absorptiometry (DXA), and cardiorespiratory parameters were measured using spiroergometry and PhysioFlow hemodynamic testing. Both interventions resulted in an increased lean mass whereas the fat mass was reduced in the leg and trunk as well as the android and gynoid regions. The content of trunk fat (in percent of the total fat) was lower and the content of the leg fat was higher in the ET-Calanus group compared with the ET-Placebo. Although both interventions resulted in similar improvements in cardiorespiratory fitness (VO2max), it was explained by an increased peripheral oxygen extraction (a-vO2diff) alone in the ET-Placebo group whereas increased values of both a-vO2diff and maximal cardiac output (COmax) were observed in the ET-Calanus group. Changes in COmax were associated with changes in systemic vascular resistance, circulating free fatty acids, and the omega-3 index. In conclusion, Calanus oil supplementation during a 4 month ET intervention in elderly women improved the cardiorespiratory function, which was due to combined central and peripheral cardiodynamic mechanisms.

Neuroblastoma survivors show signs of immunosenescence early after therapy in CD8+ T cell compartment and elevated plasma TNF‐α but in later follow‐up immune recovery comes into play. Whether the recovery phenotype is long lasting or transient remains to be elucidated, however, late adverse effects often occur in childhood cancer survivors.

Background: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders.Objectives: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss.Methods: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting.Results: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor a, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion.Conclusions: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.

Metabolism of human adipose tissue during acute exercise is monitored by microdialysis. The metabolites are analysed in the microdialysate using capillary electrophoresis (CE) on a short separation path in combination with a contactless conductivity detector (C4D). Four completely new CE/C4D methods were developed for determination of nutrients and metabolites in 10 µL of microdialysate. All methods are characterised by a short separation time and simple sample preparation based primarily on 4-fold dilution of microdialysate. The intra-day repeatability for the migration time varied in the range 0.4 – 0.9% and that for the peak area equalled 0.7 – 2.4%; the inter-day repeatability of the migration time was in the range 1.2 – 2.3% and the range for the peak area was 2.5 – 5.0%; all the values were measured as RSD. The developed determination was employed for sequenced monitoring of the levels of lactate, glycerol and branched chain amino acids in microdialysates taken from the abdominal adipose tissue during acute physical exercise. The stress test lasted 3 h and the metabolites were monitored at 15 min intervals.

It has been shown that many molecules released by adipose tissue (AT) into interstitial fluid can reach the bloodstream preferentially via lymphatic system. Worsened lymphatic drainage may alter interstitial fluid (ISF) composition and thus affect microenvironment of adipocytes. Nevertheless, the effect of lymphatic drainage on AT functions remains unknown. Therefore, we analyzed the lipolytic activity of femoral AT in two groups of premenopausal women similar in adiposity but differing in the efficiency of lymphatic drainage of lower body as assessed by lymphoscintigraphy. Levels of lipolytic markers were assessed in plasma and ISF collected by skin blister technique in femoral area. In addition, microdialysis was used to monitor lipolysis of AT in vivo. Our results indicate that worsened lymphatic drainage is associated with lower in vivo lipolytic index and reduced lipolytic responsiveness of femoral AT to adrenergic stimuli. Thus, efficiency of lymphatic drainage appears to play a role in the regulation of AT metabolism. Accordingly, worsened lymphatic drainage could contribute to the resistance of lower body AT to intentional weigh loss.

Beneficial metabolic effects of calorie restriction found in the early stage of hypocalorie diets may be caused by the modulation of metabolic and endocrine function of adipose tissue.The objective of the study was to compare metabolic and inflammation-related characteristics of sc adipose tissue (SAAT) in the early (2 d) and later (28 d) phase of a very low calorie diet (VLCD). Design, Setting, Intervention, and Patients: Seventeen moderately obese premenopausal women followed an 800 kcal/d VLCD for 28 days. Anthropometric measurements, blood sampling, and a biopsy of SAAT were performed before the diet and after 2 and 28 days of the VLCD.mRNA expression of 50 genes related to lipid metabolism, inflammation, and fibrosis were analyzed in SAAT. Secretion of adipokines was determined in SAAT explants and adipokines, fibroblast growth factor 21 (FGF21) and C-reactive protein were measured in plasma.In the early phase of the VLCD, the expression of lipolytic genes was increased, whereas the expression of lipogenic genes was significantly suppressed. The inflammatory markers in SAAT remained unchanged. At the later phase, expression of genes involved in lipogenesis and β-oxidation was markedly suppressed, whereas the expression of inflammatory markers was increased. The changes of lipogenic genes after 28 days of the VLCD correlated with FGF21 changes.The early and later phases of a VLCD differ with respect to metabolic and inflammatory responses in SAAT. The expression changes in SAAT in the early phase of the VLCD could not explain the effect of short calorie restriction on the improvement of insulin sensitivity. An interplay of SAAT with liver function during VLCD mediated by FGF21 might be suggested.

In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers. Samples of SAT and corresponding SAT-derived primary preadipocytes were obtained from two groups of women differing in age (36 vs. 72 years, n = 15 each) but matched for fat mass. mRNA levels of selected genes (lipogenesis: ACACA, FASN, SCD1, DGAT2, ELOVL6; senescence: p16, p21, NOX4, GDF15; ER stress-ATF4, XBP1s, PERK, HSPA5, GADD34, HYOU1, CHOP, EDEM1, DNAJC3) were assessed by qPCR, protein levels of GDF15 by ELISA, and mitochondrial function by the Seahorse Analyzer. Compared to the young, SAT and in vitro differentiated adipocytes from older women exhibited reduced mRNA expression of lipogenic enzymes. Out of analyzed senescence and ER stress markers, the only gene, whose expression correlated negatively with the expression of lipogenic enzymes in both SAT and adipocytes, was GDF15, a marker of not only senescence but also mitochondrial dysfunction. In line with this, inhibition of mitochondrial ATP synthase in adipocytes strongly upregulated GDF15 while reduced expression of lipogenic enzymes. Moreover, adipocytes from older women had a tendency for diminished mitochondrial capacity. Thus, a reduced lipogenic capacity of adipocytes in aged SAT appears to be linked to mitochondrial dysfunction rather than to ER stress or accumulation of senescent cells.

Hyperglycemia is suggested to be one of the drivers of the proinflammatory state observed in obese and diabetic patients.The objectives of the study was to investigate whether sc abdominal adipose tissue (scAT) could be one of the important sources of proinflammatory cytokines released in response to short-term hyperglycemia and whether this secretion capacity could be influenced by weight loss.Output of cytokines and proteins of acute phase from scAT in response to a 3-hours hyperglycemic clamp was evaluated in nine obese women in vivo using Fick's principle. Moreover, the output of cytokines was analyzed during a multiphase dietary intervention consisting of 1 month on a very low-calorie diet and subsequent 5-month weight-stabilization phase.The levels of cytokines and proteins of acute phase [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra), TNF-α, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A, and C-reactive protein] in arterial and venous plasma were measured during each dietary phase. The insulin sensitivity of scAT in respect to the antilipolytic effect of insulin during the clamp was assessed.Hyperglycemia increased the output of cytokines IL-6, MCP-1, and IL-1Ra from scAT. This effect had a tendency to be reduced after weight loss. The output of other proinflammatory substances from scAT into circulation was not detected. The diet-induced weight loss was associated with the improvement of antilipolytic insulin sensitivity in scAT.The results suggest that short-term hyperglycemia induces an increase of the output of cytokines IL-6, IL-1Ra, and MCP-1 from adipose tissue, and this deleterious hyperglycemia effect may be attenuated by the diet-induced weight reduction. This lowered responsiveness of the inflammation-related system may be an important feature of the weight reduction-induced improvement of the metabolic status of obese prediabetic individuals.

Adverse effects of aging can be delayed with life-style interventions. We examined how exercise training (ET) alone or combined with omega-3 polyunsaturated fatty acid (PUFA) affects serum and adipose tissue (AT) lipidome in older women. Fifty-five sedentary older women were included in the physical activity program and given either sunflower (Placebo) or wax esters-rich (Calanus) oil capsules for 4 months. Serum and subcutaneous abdominal AT samples were acquired while maximum rates of oxygen consumption (VO2 max), insulin sensitivity (hyperinsulinemic-euglycemic clamps) and comprehensive lipidome profiles were determined before and after the study. ET increased VO2 max in both groups. Lipidomics profiling revealed unusual serum triacylglycerols and phospholipids with ether-bound alkyls in the Calanus group, while ET generally induced shorter-chain triacylglycerols in AT, suggesting increased de novo lipogenesis. The latter was positively associated with whole-body insulin sensitivity. Unexpectedly, insulin-sensitizing lipokines from the family of branched palmitic acid esters of hydroxy stearic acid (PAHSAs) were elevated in both serum and AT after ET, while PAHSAs-containing triacylglycerols were detected in AT. ET stimulated beneficial changes in AT, including PAHSAs synthesis. Although the added value of omega-3 PUFA supplementation was not proven, our discovery can help understand the nature of the metabolic benefits of exercise.

The consumption of lipids and simple sugars induces an inflammatory response whose exact molecular trigger remains elusive. The aims of the present study were to investigate (1) whether inflammation induced by a single high-energy, high-fat meal (HFM) is associated with endoplasmic reticulum stress (ERS) in peripheral blood mononuclear cells (PBMC) and (2) whether these inflammatory and ERS responses could be prevented by the chemical chaperone ursodeoxycholic acid (UDCA). A total of ten healthy lean men were recruited to a randomised, blind, cross-over trial. Subjects were given two doses of placebo (lactose) or UDCA before the consumption of a HFM (6151 kJ; 47·4 % lipids). Blood was collected at baseline and 4 h after the HFM challenge. Cell populations and their activation were analysed using flow cytometry, and plasma levels of inflammatory cytokines were assessed by ELISA and Luminex technology. Gene expression levels of inflammatory and ERS markers were analysed in CD14+ and CD14− PBMC using quantitative RT-PCR. The HFM induced an increase in the mRNA expression levels of pro-inflammatory cytokines (IL-1β, 2·1-fold; IL-8, 2·4-fold; TNF-α, 1·4-fold; monocyte chemoattractant protein 1, 2·1-fold) and a decrease in the expression levels of miR181 (0·8-fold) in CD14+ monocytes. The HFM challenge did not up-regulate the expression of ERS markers (XBP1, HSPA5, EDEM1, DNAJC3 and ATF4) in either CD14+ or CD14− cell populations, except for ATF3 (2·3-fold). The administration of UDCA before the consumption of the HFM did not alter the HFM-induced change in the expression levels of ERS or inflammatory markers. In conclusion, HFM-induced inflammation detectable on the level of gene expression in PBMC was not associated with the concomitant increase in the expression levels of ERS markers and could not be prevented by UDCA.

Background Obesity represents a high risk factor for the development of atherosclerosis and is associated with a low-grade inflammation and activation of immune cells. Aims The aim of our study was to investigate the effect of a short-term lipid infusion on immune cells in blood and subcutaneous abdominal adipose tissue (SAAT) in obese women. Methods Seven-hour intravenous lipid/control infusions were performed in two groups of women (n = 15, n = 10, respectively). Before and at the end of the infusion, SAAT and blood samples were obtained and relative content and phenotype of immune cells were analyzed using flow cytometry. Analysis of immune cell markers, inflammation and angiogenesis markers was performed in SAAT by RT-PCR and in plasma by immunoassays. Results Relative content of CD45+/14+ and CD45+/14+/16+ populations of monocytes was reduced in circulation by 21% (p = 0.004) and by 46% (p = 0.0002), respectively, in response to hyperlipidemia, which suggested the increased adhesion of these cells to endothelium. In line with this, the levels of sICAM and sVCAM in plasma were increased by 9.4% (p = 0.016), 11.8% (p = 0.008), respectively. In SAAT, the relative content of M2 monocyte/macrophages subpopulation CD45+/14+/206+/16+ decreased by 27% (p = 0.012) and subpopulations CD14+/CD206− and CD14/+TLR4+ cells increased (p = 0.026; p = 0.049, respectively). Intralipid infusion promoted an increase of mRNA levels in SAAT: RORC (marker of proinflammatory Th17 lymphocytes) by 43% (p = 0.048), MCP-1 (78%, p = 0.028) and VEGF (68.5%, p = 0.0001). Conclusions Acute hyperlipidemia induces a proinflammatory and proatherogenic response associated with altered relative content of immune cells in blood and SAAT in obese women.

Context: Soluble CD163 (sCD163) was suggested as a biomarker of insulin sensitivity and CD163 mRNA expression representing macrophage content in adipose tissue (AT). Objective: The aim of this study was to investigate, in cross-sectional and prospective design, the relationship between sCD163 circulating levels and CD163 mRNA expression in adipose tissue and insulin sensitivity assessed by euglycemic-hyperinsulinemic clamp. Design, Setting, Participants, and Interventions: Two cohorts of subjects were examined in the study. Cohort 1 included 42 women with a wide range of body mass index (17–48 kg/m2); cohort 2 included 27 obese women who followed a dietary intervention consisting of 1 month of a very low-calorie diet and 5 months of a weight-stabilization period. Main Outcome Measures: Serum levels of CD163 and mRNA expression of CD163 and CD68 in sc and visceral (visc) AT were determined, and insulin sensitivity [expressed as glucose disposal rate (GDR)] was measured in cohort 1. In cohort 2, serum levels of CD163, mRNA expressions of CD163, CD68, and CD163-shedding factors [TNF-α-converting enzyme (TACE) and tissue inhibitor of metalloproteinase (TIMP3)] in sc AT were examined and GDR was measured before and during dietary intervention. Results: In cohort 1, circulating sCD163 correlated with CD163 mRNA levels in both sc and visc AT. sCD163 and CD163 mRNA expression in both fat depots correlated with GDR. In cohort 2, the diet-induced changes of sCD163 levels did not correlate with those of CD163, CD68, TACE, and TIMP3 mRNA levels. Although the pattern of the diet-induced change of sCD163 paralleled that of GDR, there was no correlation between the changes of these two variables. Conclusion: sCD163 correlates with CD163 mRNA expression in sc and visc AT and with whole-body insulin sensitivity in the steady-state condition. These associations are not observed with respect to the diet-induced changes during a weight-reducing hypocaloric diet.