Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

Background: Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupling in skeletal muscle has not extensively been studied in relation to adaptive thermogenesis in humans. Therefore we hypothesized that cold-induced adaptive thermogenesis in humans is accompanied by an increase in mitochondrial uncoupling in skeletal muscle. Methodology/Principal Findings: The metabolic response to mild cold exposure in 11 lean, male subjects was measured in a respiration chamber at baseline and mild cold exposure. Skeletal muscle mitochondrial uncoupling (state 4) was measured in muscle biopsies taken at the end of the respiration chamber stays. Mild cold exposure caused a significant increase in 24h energy expenditure of 2.8 % (0.32 MJ/day, range of 20.21 to 1.66 MJ/day, p,0.05). The individual increases in energy expenditure correlated to state 4 respiration (p,0.02, R 2 = 0.50). Conclusions/Significance: This study for the first time shows that in humans, skeletal muscle has the intrinsic capacity for cold induced adaptive thermogenesis via mitochondrial uncoupling under physiological conditions. This opens possibilitie

Pulsar polarisation below 200 MHz: Average profiles and propagation effects

Aims: We present the highest-quality polarisation profiles to date of 16 non-recycled pulsars and four millisecond pulsars, observed below 200 MHz with the LOFAR high-band antennas. Based on the observed profiles, we perform an initial investigation of expected observational effects resulting from the propagation of polarised emission in the pulsar magnetosphere and the interstellar medium. Methods: The polarisation data presented in this paper have been calibrated for the geometric-projection and beam-shape effects that distort the polarised information as detected with the LOFAR antennas. We have used RM Synthesis to determine the amount of Faraday rotation in the data at the time of the observations. The ionospheric contribution to the measured Faraday rotation was estimated using a model of the ionosphere. To study the propagation effects, we have compared our low-frequency polarisation observations with archival data at 240, 400, 600, and 1400 MHz. Results: The predictions of magnetospheric birefringence in pulsars have been tested using spectra of the pulse width and fractional polarisation from multifrequency data. The derived spectra offer only partial support for the expected effects of birefringence on the polarisation properties, with only about half of our sample being consistent with the model's predictions. It is noted that for some pulsars these measurements are contaminated by the effects of interstellar scattering. For a number of pulsars in our sample, we have observed significant variations in the amount of Faraday rotation as a function of pulse phase, which is possibly an artefact of scattering. These variations are typically two orders of magnitude smaller than that observed at 1400 MHz by Noutsos et al. (2009), for a different sample of southern pulsars. In this paper we present a possible explanation for the difference in magnitude of this effect between the two frequencies, based on scattering. Finally, we have estimated the magnetospheric emission heights of low-frequency radiation from four pulsars, based on the phase lags between the flux-density and the PA profiles, and the theoretical framework of Blaskiewicz et al. (1991, ApJ, 370, 643). These estimates yielded heights of a few hundred km; at least for PSR B1133+16, this is consistent with emission heights derived based on radius-to-frequency mapping, but is up to a few times larger than the recent upper limit based on pulsar timing. Conclusions: Our work has shown that models, like magnetospheric birefringence, cannot be the sole explanation for the complex polarisation behaviour of pulsars. On the other hand, we have reinforced the claim that interstellar scattering can introduce a rotation of the PA with frequency that is indistinguishable from Faraday rotation and also varies as a function of pulse phase. In one case, the derived emission heights appear to be consistent with the predictions of radius-to-frequency mapping at 150 MHz, although this interpretation is subject to a number of systematic uncertainties

The Pe of Perfectionism Concern Over Mistakes Predicts the Amplitude of a Late Frontal Error Positivity

<p>The present research investigates the association between concern over mistakes (CoM), a facet of the personality style of perfectionism, and the error positivity (Pe), a response-locked event-related brain potential that relates to error-awareness. Sixteen healthy right-handed female participants performed a flanker task, during which response-locked event-related potentials were measured. CoM was related to a larger Pe at frontal electrodes in a late (400-500 ms post-response) time interval. This frontal late Pe was not related to general trait anxiety. An earlier (150-350 ms) Pe with a more centroparietal maximum was positively associated with accuracy in the flanker task. CoM was not related to the amplitude of the error-related negativity. Exploratory analyses revealed correlations of CoM with reduced state arousal and late positive potential responses to emotional aspects of the feedback stimuli. The latter findings suggest the possibility that, instead of to an increased Pe, high CoM related to a decreased emotional arousal-sensitive stimulus-preceding negativity in anticipation of negative feedback. CoM may thus be associated with avoidant coping with the negative emotional impact of error feedback.</p>

Regression of increases in total daily energy expenditure (MJ/day) and state 4 respiration (pmol O₂/(s·mg muscle·CS activity)) (p<0.02, R² = 0.50).

<p>Regression of increases in total daily energy expenditure (MJ/day) and state 4 respiration (pmol O₂/(s·mg muscle·CS activity)) (p<0.02, R² = 0.50).</p

Baseline and mild cold values of a) total daily energy expenditure, b) activity, c) state 4 respiration, and d) state 3 respiration.

<p>The figures show mean (±SEM) in both situations. * p<0.05, ** p<0.01</p

High Prevalence of Physical Frailty Among Community-Dwelling Malnourished Older Adults-A Systematic Review and Meta-Analysis

Background: Malnutrition and frailty are two geriatric syndromes that significantly affect independent living and health in community-dwelling older adults. Although the pathophysiology of malnutrition and physical frailty share common pathways, it is unknown to what extent these syndromes overlap and how they relate to each other. Methods: A systematic review was performed resulting in a selection of 28 studies that assessed both malnutrition and frailty in community-dwelling older adults. Furthermore, a meta-analysis was performed on 10 studies that used Mini- Nutritional Assessment and the Fried frailty phenotype to estimate the prevalence of malnutrition within physical frailty and vice versa. Results: In the systematic review, 25 of the 28 studies used the Mini-Nutritional Assessment (long or short form) for malnutrition screening. For frailty assessment, 23 of the 28 studies focused on the physical frailty phenotype, of which 19 followed the original Fried phenotype. Fifteen studies analyzed the association between malnutrition and frailty, which was significant in 12 of these. The meta-analysis included 10 studies with a total of 5447 older adults. In this pooled population of community-dwelling older adults [mean (standard deviation) age: 77.2 (6.7) years], 2.3% was characterized as malnourished and 19.1% as physically frail. The prevalence of malnutrition was significantly associated with the prevalence of physical frailty (P < .0001). However, the syndromes were not interchangeable: 68% of the malnourished older adults was physically frail, whereas only 8.4% of the physical frail population was malnourished. Conclusions: The systematic review and meta-analysis revealed that malnutrition and physical frailty in community-dwelling older adults are related, but not interchangeable geriatric syndromes. Two out of 3 malnourished older adults were physically frail, whereas close to 10% of the physically frail older adults was identified as malnourished

Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults : the PROVIDE study

Background A chronic low-grade infammatory profle (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for efects of nutritional supplementation on CLIP is limited. Aim To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein afected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. Methods Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4–9) and a body mass index of 20–30 kg/m2 were randomly allocated to two daily servings of active (n=137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n=151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH) D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. Results IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p=0.006 and p&lt;0.001, respectively). For IL-6 a signifcant time × treatment interaction (p=0.046) was observed, with no signifcant change over time in the active group (p=0.155) compared to control (signifcant increase p=0.012). IL-8 showed an overall signifcant decrease (p=0.03). The change in pre-albumin was a signifcant predictor for changes in IL-6 after 13 weeks. Conclusions We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations

Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment