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1.
Double transcranial direct current stimulation of the brain increases cerebral energy levels and systemic glucose tolerance in men.
Wardzinski, EK, Friedrichsen, L, Dannenberger, S, Kistenmacher, A, Melchert, UH, Jauch-Chara, K, Oltmanns, KM
Journal of neuroendocrinology. 2019;(4):e12688
Abstract
Transcranial direct current stimulation (tDCS) is a neuromodulatory method that has been tested experimentally and has already been used as an adjuvant therapeutic option to treat a number of neurological disorders and neuropsychiatric diseases. Beyond its well known local effects within the brain, tDCS also transiently promotes systemic glucose uptake and reduces the activity of the neurohormonal stress axes. We aimed to test whether the effects of a single tDCS application could be replicated upon double stimulation to persistently improve systemic glucose tolerance and stress axes activity in humans. In a single-blinded cross-over study, we examined 15 healthy male volunteers. Anodal tDCS vs sham was applied twice in series. Systemic glucose tolerance was investigated by the standard hyperinsulinaemic-euglycaemic glucose clamp procedure, and parameters of neurohormonal stress axes activity were measured. Because tDCS-induced brain energy consumption has been shown to be part of the mechanism underlying the assumed effects, we monitored the cerebral high-energy phosphates ATP and phosphocreatine by 31 phosphorus magnetic resonance spectroscopy. As hypothesised, analyses revealed that double anodal tDCS persistently increases glucose tolerance compared to sham. Moreover, we observed a significant rise in cerebral high-energy phosphate content upon double tDCS. Accordingly, the activity of the neurohormonal stress axes was reduced upon tDCS compared to sham. Our data demonstrate that double tDCS promotes systemic glucose uptake and reduces stress axes activity in healthy humans. These effects suggest that repetitive tDCS may be a future non-pharmacological option for combating glucose intolerance in type 2 diabetes patients.
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2.
Competition for nutrients and its role in controlling immune responses.
Kedia-Mehta, N, Finlay, DK
Nature communications. 2019;(1):2123
Abstract
Changes in cellular metabolism are associated with the activation of diverse immune subsets. These changes are fuelled by nutrients including glucose, amino acids and fatty acids, and are closely linked to immune cell fate and function. An emerging concept is that nutrients are not equally available to all immune cells, suggesting that the regulation of nutrient utility through competitive uptake and use is important for controlling immune responses. This review considers immune microenvironments where nutrients become limiting, the signalling alterations caused by insufficient nutrients, and the importance of nutrient availability in the regulation of immune responses.
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3.
The effect of foot orthoses and insoles on running economy and performance in distance runners: A systematic review and meta-analysis.
Crago, D, Bishop, C, Arnold, JB
Journal of sports sciences. 2019;(22):2613-2624
Abstract
Foot orthoses and insoles are prescribed to runners, however their impact on running economy and performance is uncertain. The aim of this systematic review and meta-analysis was to determine the effect of foot orthoses and insoles on running economy and performance in distance runners. Seven electronic databases were searched from inception until June 2018. Eligible studies investigated the effect of foot orthoses or insoles on running economy (using indirect calorimetry) or running performance. Standardised mean differences (SMDs) were computed and meta-analyses were conducted using random effects models. Methodological quality was assessed using the Quality Index. Nine studies met the criteria and were included: five studies investigated the effect of foot orthoses on running economy and four investigated insoles. Foot orthoses were associated with small negative effects on running economy compared to no orthoses (SMD 0.42 [95% CI 0.17,0.72] p = 0.007). Shock absorbing insoles were also associated with negative effects on running economy, but an imprecise estimate (SMD 0.26 [95% CI -0.33,0.84] p = 0.83). Quality Index scores ranged from 4 to 15 out of 17. Foot orthoses and shock absorbing insoles may adversely affect running economy in distance runners. Future research should consider their potential effects on running performance.
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4.
High-Fat Breakfast Meal Replacement in Overweight and Obesity: Implications on Body Composition, Metabolic Markers, and Satiety.
Smith-Ryan, AE, Hirsch, KR, Blue, MNM, Mock, MG, Trexler, ET
Nutrients. 2019;(4)
Abstract
The purpose of this paper was to determine the effect of replacing breakfast with a high-fat drink on fat mass (FM), lean mass (LM), percent body fat (%BF), visceral fat (VAT), resting metabolic rate (RMR), fuel utilization (RER), blood lipids and satiety in overweight and obese adults. Healthy adults (n = 42; 21 Females; body mass index (BMI): 32.8 ± 4.6 kg·m-2) were randomized to control (CON; n = 21) or meal replacement (MRP; n = 22) groups. Body composition was measured using a four-compartment model; RMR and RER were assessed from indirect calorimetry. The MRP (70% fat) was consumed once daily for eight weeks. For males, there was no change (p > 0.05) in FM (mean difference (MD) = 0.41 ± 1.19 kg], %BF MD = 0.50 ± 1.09%, LM MD = -0.64 ± 1.79 kg, or VAT MD = -0.31 ± 1.36 cm for MRP versus CON. Similarly, no differences for females for FM MD = -0.73 ± 1.37 kg, %BF MD = -0.57 ± 1.26%, LM MD = 0.31 ± 1.37 kg, or VAT MD -0.83 ± 1.2 cm. HDL was significantly reduced in the MRP group for females (adjusted mean change: -6.41 ± 4.44 units, p = 0.018). There was no effect on RMR or RER. Satiety increased in the afternoon for MRP (p = 0.021). Despite high fat, no negative impact on lipids resulted; increased satiety may be beneficial for controlling afternoon cravings, but does not affect body composition.
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5.
Differences in energy expenditure in human donor milk versus formula milk in preterm newborns: A crossover study.
Soares, FVM, Abranches, AD, Méio, MDBB, Gomes, SC, Villela, LD, Moreira, MEL
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:1-4
Abstract
OBJECTIVE The aim of this study was to compare the ratio between energy expenditure and caloric density in human donor milk versus formula milk in preterm newborn infants. METHODS This was a crossover, randomized clinical trial with 29 preterm newborn infants receiving full diet. The infants were randomly assigned to receive either human milk or formula milk alternating, after a 24-h period. Energy expenditure was evaluated by indirect calorimetry. Total calorie and macronutrient values in the human milk were calculated individually with infrared technique; energy expenditure/caloric density ratio was calculated. RESULTS Human donor milk energy expenditure/caloric density ratio was significantly greater than in formula milk at all time points. The total mean was 1.04 ± 0.27 for the human milk and 0.81 ± 0.11 for the formula. However, when we analyzed a subgroup of newborns that received human donor milk with >60 kcal/100 mL, there was no statistical difference (P = 0.36). The mean calorie values were 58.9 kcal/100 mL (human donor milk) and 81.4 kcal/100 mL (formula milk). CONCLUSION Formula milk produced a better metabolic response than human donor milk. Human donor milk with higher caloric content showed no difference from formula, so the use of human donor milk with more caloric density should be reinforced.
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6.
Wheat Albumin Increases the Ratio of Fat to Carbohydrate Oxidation during the Night in Healthy Participants: A Randomized Controlled Trial.
Saito, S, Sakuda, T, Shudo, A, Sugiura, Y, Osaki, N
Nutrients. 2019;(1)
Abstract
Not only are energy expenditure (EE) and the respiratory quotient (RQ) parameters of the energy nutrient utilization and energy balance, they are also related to the development of obesity. In this study, post-meal night-time energy metabolism was investigated following the oral ingestion of wheat albumin (WA) with a late evening meal. A randomly assigned, double-blind, placebo-controlled crossover trial for a single oral ingestion in healthy participants was completed. The participants ingested the placebo (PL) or WA (1.5 g) containing tablets 3 minutes before the late evening meal at 22:00 hour, and energy metabolism was measured using a whole-room indirect calorie meter until wake-up. The participants were in bed from 00:00 hour until 06:30 hour. Twenty healthy participants completed the trial and were included in the analyses. Night-time RQ and carbohydrate oxidation were significantly lower following the WA treatment as compared with the PL treatment. Although the total EE was not significantly different between treatments, postprandial fat oxidation was significantly higher following the WA treatment as compared with the PL treatment. In conclusion, WA has the potential to shift the energy balance to a higher ratio of fat to carbohydrate oxidation during the night.
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7.
Acute Ingestion of a Mixed Flavonoid and Caffeine Supplement Increases Energy Expenditure and Fat Oxidation in Adult Women: A Randomized, Crossover Clinical Trial.
Nieman, DC, Simonson, A, Sakaguchi, CA, Sha, W, Blevins, T, Hattabaugh, J, Kohlmeier, M
Nutrients. 2019;(11)
Abstract
This randomized, double-blinded, crossover study measured the acute effect of ingesting a mixed flavonoid-caffeine (MFC) supplement compared to placebo (PL) on energy expenditure (EE) and fat oxidation (FATox) in a metabolic chamber with premenopausal women (n = 19, mean ± SD, age 30.7 ± 8.0 year, BMI 25.7 ± 3.4 kg/m2). The MFC supplement (658 mg flavonoids, split dose 8:30, 13:00) contained quercetin, green tea catechins, and anthocyanins from bilberry extract, and 214 mg caffeine. Participants were measured twice in a metabolic chamber for a day, four weeks apart, with outcomes including 22 h EE (8:30-6:30), substrate utilization from the respiratory quotient (RQ), plasma caffeine levels (16:00), and genotyping for the single-nucleotide polymorphism (SNP) rs762551. Areas under the curve (AUC) for metabolic data from the MFC and PL trials were calculated using the trapezoid rule, with a mixed linear model (GLM) used to evaluate the overall treatment effect. The 22 h oxygen consumption and EE were significantly higher with MFC than PL (1582 ± 143, 1535 ± 154 kcal/day, respectively, p = 0.003, trial difference of 46.4 ± 57.8 kcal/day). FATox trended higher for MFC when evaluated using GLM (99.2 ± 14.0, 92.4 ± 14.4 g/22 h, p = 0.054). Plasma caffeine levels were significantly higher in the MFC versus PL trial (5031 ± 289, 276 ± 323 ng/mL, respectively, p < 0.001). Trial differences for 22 h EE and plasma caffeine were unrelated after controlling for age and body mass (r = -0.249, p = 0.139), and not different for participants with the homozygous allele 1, A/A, compared to C/A and C/C (p = 0.50 and 0.56, respectively). In conclusion, EE was higher for MFC compared to PL, and similar to effects estimated from previous trials using caffeine alone. A small effect of the MFC on FATox was measured, in contrast to inconsistent findings previously reported for this caffeine dose. The trial variance for 22 h EE was not significantly related to the variance in plasma caffeine levels or CYP1A2*1F allele carriers and non-carriers.
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8.
Identifying and targeting cancer-specific metabolism with network-based drug target prediction.
Pacheco, MP, Bintener, T, Ternes, D, Kulms, D, Haan, S, Letellier, E, Sauter, T
EBioMedicine. 2019;:98-106
Abstract
BACKGROUND Metabolic rewiring allows cancer cells to sustain high proliferation rates. Thus, targeting only the cancer-specific cellular metabolism will safeguard healthy tissues. METHODS We developed the very efficient FASTCORMICS RNA-seq workflow (rFASTCORMICS) to build 10,005 high-resolution metabolic models from the TCGA dataset to capture metabolic rewiring strategies in cancer cells. Colorectal cancer (CRC) was used as a test case for a repurposing workflow based on rFASTCORMICS. FINDINGS Alternative pathways that are not required for proliferation or survival tend to be shut down and, therefore, tumours display cancer-specific essential genes that are significantly enriched for known drug targets. We identified naftifine, ketoconazole, and mimosine as new potential CRC drugs, which were experimentally validated. INTERPRETATION The here presented rFASTCORMICS workflow successfully reconstructs a metabolic model based on RNA-seq data and successfully predicted drug targets and drugs not yet indicted for colorectal cancer. FUND This study was supported by the University of Luxembourg (IRP grant scheme; R-AGR-0755-12), the Luxembourg National Research Fund (FNR PRIDE PRIDE15/10675146/CANBIO), the Fondation Cancer (Luxembourg), the European Union's Horizon2020 research and innovation programme under the Marie Sklodowska- Curie grant agreement No 642295 (MEL-PLEX), and the German Federal Ministry of Education and Research (BMBF) within the project MelanomSensitivity (BMBF/BM/7643621).
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9.
The role of hormonal, metabolic and inflammatory biomarkers on sleep and appetite in drug free patients with major depression: A systematic review.
Caroleo, M, Carbone, EA, Primerano, A, Foti, D, Brunetti, A, Segura-Garcia, C
Journal of affective disorders. 2019;:249-259
Abstract
BACKGROUND Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e. decreased or increased appetite, changes in body weight and sleep disturbances, described as 'melancholic' or 'atypical' features of a depressive episode, are the most variable symptoms among patients with MDD. We hypothesized biomarkers differences underlying this neurovegetative variability in major depression. METHODS We systematically reviewed, according to the PRISMA guidelines, the role of specific metabolic, hormonal and inflammatory biomarkers in drug-free MDD patients, that could have neurobiological effects on appetite, weight regulation and circadian rhythms, influencing eating behaviour and sleep patterns. All studies regarding the co-occurrence of disturbed sleep and appetite were examined. RESULTS Besides the well-known leptin and ghrelin, other biomarkers such as BDNF, VEGF, NPY, orexin, and the recent discovered nesfatin-1 seem to be involved in neurovegetative changes in depressive disorders playing a role in the regulation of affective states, stress reactions and sleep patterns. Interestingly, based on the existing evidence, ghrelin, orexin and nesfatin-1 could be linked both to sleep and appetite regulation in depressed patients. LIMITATIONS Heterogeneous studies with low sample size. CONCLUSIONS Despite the wide heterogeneity of results, studies on biomarkers of appetite and sleep in MDD are an interesting field of research to explain the neurobiological substrates of depressive symptoms that deserve further investigation.
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10.
5'-Adenosine monophosphate-activated protein kinase: A potential target for disease prevention by curcumin.
Soltani, A, Salmaninejad, A, Jalili-Nik, M, Soleimani, A, Javid, H, Hashemy, SI, Sahebkar, A
Journal of cellular physiology. 2019;(3):2241-2251
Abstract
Curcumin (diferuloylmethane), a yellowish agent extracted from turmeric, is a bioactive compound known for its anti-inflammatory, antiproliferative, antidiabetic, and anticancer activities. Multiple lines of evidence have indicated that curcumin regulates several regulatory proteins in the cellular signal transduction pathway. AMP-activated protein kinase (AMPK) is one of the central regulators of cellular metabolism and energy homeostasis, which is activated in response to increasing cellular adenosine monophosphate/adenosine triphosphate ratio. AMPK plays a critical role in regulating growth and reprogramming metabolism and is linked to several cellular processes including apoptosis and inflammation. Recently, it has been demonstrated that AMPK is a new molecular target affected by curcumin and its derivatives. In this review, we discuss recent findings on the targeting of AMPK signaling by curcumin and the resulting impact on the pathogenesis of proinflammatory diseases. We also highlight the therapeutic value of targeting AMPK by curcumin in the prevention and treatment of proinflammatory diseases, including cancers, atherosclerosis, and diabetes.