Suppressed bone turnover in obesity: a link to energy metabolism? A case-control study

CONTEXT\nObservations in rodents suggest that osteocalcin (OC) participates in glucose metabolism. Based on human studies, it remains unclear whether circulating OC is simply a bone turnover marker (BTM) or also a mediator in interactions between the skeleton and glucose homeostasis.\nOBJECTIVE\nThe objective of the study was to determine the responses of BTMs, including OC, to oral glucose tolerance test (OGTT) in a case-control setting.\nDESIGN AND PATIENTS\nThirty-four normoglycemic young adults [mean age 19 y (SD 2.3)] with severe childhood-onset obesity and their gender- and age-matched nonobese controls underwent a standard 2-hour OGTT.\nMAIN OUTCOME MEASURES\nGlucose, insulin, and six BTMs including total and carboxylated OC (cOC) were determined at baseline and at 30, 60, 90, and 120 minutes during OGTT.\nRESULTS\nThe obese and control subjects were similar in height; the mean body mass indices were 40.4 and 21.9 kg/m(2), respectively. The homeostasis model assessment index was 2.7 times greater in the obese subjects. All BTMs, except bone-specific alkaline phophatase, were lower in the obese subjects compared with the controls: the differences at baseline were 40%, 35%, 17%, 31%, and 32% for N-terminal propeptides of type I collagen, cross-linked telopeptides of type I collagen, tartrate-resistant acid phosphatase, total OC, and carboxylated OC (P &lt; .05 for all) after adjusting for whole-body bone area. All BTMs decreased during OGTT. The relative values for the OGTT responses for total, but not for cOC (measured as area under the curve) differed between the two groups (P = .029 and P = .139, respectively): the decrease in total OC during the OGTT was less pronounced in the obese subjects. Responses in other BTMs were similar between the groups. No associations were observed between glucose metabolism and OCs during OGTT with linear regression.\nCONCLUSIONS\nBone turnover markers were substantially lower in obese subjects compared with controls. Total OC and cOC showed less pronounced decrease during the OGTT in obese subjects compared with controls, whereas other BTMs responded similarly in the two groups. The role of OC, if anything, in glucose homeostasis is indirect and may be mediated via other factors than glucose or insulin.</p

Theory of the Half-Polarized Quantum Hall States

We report a theoretical analysis of the half-polarized quantum Hall states observed in a recent experiment. Our numerical results indicate that the ground state energy of the quantum Hall $\nu= 2/3$ and $\nu= 2/5$ states versus spin polarization has a downward cusp at half the maximal spin polarization. We map the two-component fermion system onto a system of excitons and describe the ground state as a liquid state of excitons with non-zero values of exciton angular momentum.Comment: 4 pages (RevTeX), 3 figures (PostScript), added reference

Weight Loss Trajectories in Healthy Weight Coaching : Cohort Study

Background: As global obesity prevalence continues to increase, there is a need for accessible and affordable weight management interventions, such as web-based programs. Objective: This paper aims to assess the outcomes of healthy weight coaching (HWC), a web-based obesity management program integrated into standard Finnish clinical care. Methods: HWC is an ongoing, structured digital 12-month program based on acceptance and commitment therapy. It includes weekly training sessions focused on lifestyle, general health, and psychological factors. Participants received remote one-on-one support from a personal coach. In this real-life, single-arm, prospective cohort study, we examined the total weight loss, weight loss profiles, and variables associated with weight loss success and program retention in 1189 adults (963 women) with a BMI >25 kg/m(2) among participants of the program between October 2016 and March 2019. Absolute (kg) and relative (%) weight loss from the baseline were the primary outcomes. We also examined the weight loss profiles, clustered based on the dynamic time-warping distance, and the possible variables associated with greater weight loss success and program retention. We compared different groups using the Mann-Whitney test or Kruskal-Wallis test for continuous variables and the chi-squared test for categorical variables. We analyzed changes in medication using the McNemar test. Results: Among those having reached the 12-month time point (n=173), the mean weight loss was 4.6% (SE 0.5%), with 43% (n=75) achieving clinically relevant weight loss (>= 5%). Baseline BMI >= 40 kg/m(2) was associated with a greater weight loss than a lower BMI (mean 6.6%, SE 0.9%, vs mean 3.2%, SE 0.6%; P=.02). In addition, more frequent weight reporting was associated with greater weight loss. No significant differences in weight loss were observed according to sex, age, baseline disease, or medication use. The total dropout rate was 29.1%. Dropouts were slightly younger than continuers (47.2, SE 0.6 years vs 49.2, SE 0.4 years; P=.01) and reported their weight less frequently (3.0, SE 0.1 entries per month vs 3.3, SE 0.1 entries per month; P Conclusions: A comprehensive web-based program such as HWC is a potential addition to the repertoire of obesity management in a clinical setting. Heavier patients lost more weight, but weight loss success was otherwise independent of baseline characteristics.Peer reviewe

Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

The authors describe a new approach to studying cellular lipid profiles and propose a compensatory mechanism that may help maintain the normal membrane function of adipocytes in the context of obesity

A southern bottlenose whale examined in the Antarctic

This paper mainly concerns the dissection of a lactating female southern bottlenose whale Hyperoodon planifrons especially shot and worked up for the author in the Antarctic 61°09'S, 86°44'E on 10 March 1948. The skeleton is in the British Museum (Natural History). A comparison with what is known of the female northern bottlenose whale H. ampullatus shows no differences in morphometry, body colour, external characters, digestive system and reproductive system, parasites and the vertebral formula and the digital formula of the flipper. There remain acknowledged differences in the skull which may be reduced or perhaps even disappear when further comparisons are attempted between skulls from males and females of similar ages. There is also the confusion when identifying ziphiid whales at sea. These observations have suggested to the author that there may be only one Hyperoodon species with a continuous distribution north and south. But Dalebout et al. (2004), applying DNA sequencies in molecular taxonomy, have now shown that all 21 species of ziphiid whales are valid

Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.Peer reviewe

Theory of Incompressible States in a Narrow Channel

We report on the properties of a system of interacting electrons in a narrow channel in the quantum Hall effect regime. It is shown that an increase in the strength of the Coulomb interaction causes abrupt changes in the width of the charge-density profile of translationally invariant states. We derive a phase diagram which includes many of the stable odd-denominator states as well as a novel fractional quantum Hall state at lowest half-filled Landau level. The collective mode evaluated at the half-filled case is strikingly similar to that for an odd-denominator fractional quantum Hall state.Comment: 4 pages, REVTEX, and 4 .ps file

Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men

Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.Peer reviewe

Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating&nbsp;levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health