Significance of adipose tissue characteristics for development of metabolic complications in obesity

Background: Obesity is closely related to development of insulin resistance and dyslipidemia. Intrinsic properties of adipose tissue are also of great importance for obesity related comorbidity. The aim of this thesis was to gain further knowledge of adipose depot specific effects of how fat cell size and lipolysis, as well as removal of a large portion of the visceral fat depot, affect metabolic risk. Methods: All subjects were from a cohort of 81 obese women undergoing gastric bypass operation. Study I and study III were cross-sectional studies using baseline data, whereas study II and IV were longitudinal studies which also included an examination two years post- surgery. Insulin sensitivity was evaluated with hyperinsulinemic euglycemic clamp. Subcutaneous and visceral fat biopsies were obtained to determine mean fat cell size and lipolysis. Results: Study I showed that subcutaneous fat cell size correlated with insulin sensitivity (r= -0.40 p= 0.004) and visceral fat cell size correlated with dyslipidemia (r=0.32-0.38 p= 0.0006-0.003). Subjects with combined hyperplasia (many small fat cells) in both subcutaneous and visceral fat depots had a favorable metabolic profile compared to subjects with combined hypertrophy (few but large fat cells) (p= 0.0001-0.02). Study II focused on changes in fat cell size and insulin sensitivity following weight reduction induced by bariatric surgery in obese women. Changes in subcutaneous fat cell size correlated with improved insulin sensitivity independently of changes in subcutaneous fat mass (r=0.32 p= 0.04). Study III investigated depot specific relations between lipolysis and cardiovascular risk factors. Visceral but not subcutaneous fat cell lipolysis correlated with several cardiovascular risk factors including insulin resistance, high plasma triglycerides and blood pressure (r= 0.28-0.44 p= 0.0001-0.02). Visceral fat cell lipolysis was also increased in subjects with metabolic syndrome (F= 8.3 p= 0.005). Study IV, designed as a randomized double blind controlled trial, investigated the 2-year effects of omentectomy in conjunction with gastric bypass operation on insulin sensitivity and the lipid profile. Eighty-one subjects were included in the study and 62 were re-examined two years post-surgery. Omentectomy did not give any additional positive metabolic effects, neither in the primary outcome measure insulin sensitivity (p= 0.54), nor the secondary outcome measures such as lipid status or weight reduction (p= 0.17-0.98). Conclusion: The studies in this thesis highlight that intrinsic factors of adipose tissue, such as fat cell size and lipolysis, independently of fat mass, are important for metabolic complications in obesity. A mere removal of a substantial part of the visceral fat depot does not enhance improved metabolic outcome after gastric bypass operation, suggesting that a metabolic change in adipose tissue and changes in fat cell size are important to achieve positive effects of fat mass reduction

Phylogenetic Signals of Salinity and Season in Bacterial Community Composition Across the Salinity Gradient of the Baltic Sea

Understanding the key processes that control bacterial community composition has enabled predictions of bacterial distribution and function within ecosystems. In this study, we used the Baltic Sea as a model system to quantify the phylogenetic signal of salinity and season with respect to bacterioplankton community composition. The abundances of 16S rRNA gene amplicon sequencing reads were analyzed from samples obtained from similar geographic locations in July and February along a brackish to marine salinity gradient in the Baltic Sea. While there was no distinct pattern of bacterial richness at different salinities, the number of bacterial phylotypes in winter was significantly higher than in summer. Bacterial community composition in brackish vs. marine conditions, and in July vs. February was significantly different. Non-metric multidimensional scaling showed that bacterial community composition was primarily separated according to salinity and secondly according to seasonal differences at all taxonomic ranks tested. Similarly, quantitative phylogenetic clustering implicated a phylogenetic signal for both salinity and seasonality. Our results support that global patterns of bacterial community composition with respect to salinity and season are the result of phylogenetically clustered ecological preferences with stronger imprints from salinity

Association of Phosphodiesterase-5 Inhibitors Versus Alprostadil With Survival in Men With Coronary Artery Disease

Abstract Background Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI). Objectives This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease. Methods All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil. Results This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1. Conclusions In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design

Ghrelin increases intake of rewarding food in rodents

We investigated whether ghrelin action at the level of the ventral tegmental area (VTA), a key node in the mesolimbic reward system, is important for the rewarding and motivational aspects of the consumption of rewarding/palatable food. Mice with a disrupted gene encoding the ghrelin receptor (GHS-R1A) and rats treated peripherally with a GHS-R1A antagonist both show suppressed intake of rewarding food in a free choice (chow/rewarding food) paradigm. Moreover, accumbal dopamine release induced by rewarding food was absent in GHS-R1A knockout mice. Acute bilateral intra-VTA administration of ghrelin increased 1-hour consumption of rewarding food but not standard chow. In comparison with sham rats, VTA-lesioned rats had normal intracerebroventricular ghrelin-induced chow intake, although both intake of and time spent exploring rewarding food was decreased. Finally, the ability of rewarding food to condition a place preference was suppressed by the GHS-R1A antagonist in rats. Our data support the hypothesis that central ghrelin signaling at the level of the VTA is important for the incentive value of rewarding food

Multi-Decadal Decline of Mercury in the North Atlantic Atmosphere Explained by Changing Subsurface Seawater Concentrations

[1] We analyze 1977–2010 trends in atmospheric mercury (Hg) from 21 ship cruises over the North Atlantic (NA) and 15 over the South Atlantic (SA). We find a steep 1990–2009 decline of −0.046 ± 0.010 ng m−3 a−1 (−2.5% a−1) over the NA (steeper than at Northern Hemispheric land sites) but no significant decline over the SA. Surface water Hg0 measurements in the NA show a decline of −5.7% a−1since 1999, and limited subsurface ocean data show an ∼80% decline from 1980 to present. We use a coupled global atmosphere-ocean model to show that the decline in NA atmospheric concentrations can be explained by decreasing oceanic evasion from the NA driven by declining subsurface water Hg concentrations. We speculate that this large historical decline of Hg in the NA Ocean could have been caused by decreasing Hg inputs from rivers and wastewater and by changes in the oxidant chemistry of the atmospheric marine boundary layer.Engineering and Applied Science

The constraint equations for the Einstein-scalar field system on compact manifolds

We study the constraint equations for the Einstein-scalar field system on compact manifolds. Using the conformal method we reformulate these equations as a determined system of nonlinear partial differential equations. By introducing a new conformal invariant, which is sensitive to the presence of the initial data for the scalar field, we are able to divide the set of free conformal data into subclasses depending on the possible signs for the coefficients of terms in the resulting Einstein-scalar field Lichnerowicz equation. For many of these subclasses we determine whether or not a solution exists. In contrast to other well studied field theories, there are certain cases, depending on the mean curvature and the potential of the scalar field, for which we are unable to resolve the question of existence of a solution. We consider this system in such generality so as to include the vacuum constraint equations with an arbitrary cosmological constant, the Yamabe equation and even (all cases of) the prescribed scalar curvature problem as special cases.Comment: Minor changes, final version. To appear: Classical and Quantum Gravit

Thermodynamic and Kinetic Parameters for Calcite Nucleation on Peptoid and Model Scaffolds:A Step toward Nacre Mimicry

The production of novel composite materials, assembled using biomimetic polymers known as peptoids (N-substituted glycines) to nucleate CaCO3, can open new pathways for advanced material design. However, a better understanding of the heterogeneous CaCO3 nucleation process is a necessary first step. We determined the thermodynamic and kinetic parameters for calcite nucleation on self-assembled monolayers (SAMs) of nanosheet-forming peptoid polymers and simpler, alkanethiol analogues. We used nucleation rate studies to determine the net interfacial free energy (γ net) for the peptoid-calcite interface and for SAMs terminated with carboxyl headgroups, amine headgroups, or a mix of the two. We compared the results with γ net determined from dynamic force spectroscopy (DFS) and from density functional theory (DFT), using COSMO-RS simulations. Calcite nucleation has a lower thermodynamic barrier on the peptoid surface than on carboxyl and amine SAMs. From the relationship between nucleation rate (J 0) and saturation state, we found that under low-saturation conditions, i.e. <3.3 (pH 9.0), nucleation on the peptoid substrate was faster than that on all of the model surfaces, indicating a thermodynamic drive toward heterogeneous nucleation. When they are taken together, our results indicate that nanosheet-forming peptoid monolayers can serve as an organic template for CaCO3 polymorph growth