Effects of genetic loci associated with central obesity on adipocyte lipolysis

Objectives: Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis. Subjects and Methods: Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7–62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score. Results: The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis. Significance: This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes

Essays on Inequality and Macroeconomic Stability

This dissertation consists of three chapters. . . Chapter 1: Aggregate Wealth and Its Distribution as Determinants of Financial Crises: Panel Evidence This essay investigates the relationship between wealth inequality and financial crises across a panel of nine advanced economies over the past 100 years. While substantiation of a role for income inequality is ambiguous in the literature, evidence is presented suggesting a unique capacity for the accumulation of assets to increase the likelihood of a future financial crisis episode. Testing long-run panel data with a reduced form, two-way fixed effects model, estimates suggest that increasing wealth inequality, in an economy with high levels of aggregate wealth as measured by the wealth-income ratio, has a significantly positive and increasing marginal effect on the likelihood of future financial crises, particularly stock market crashes. Predicted probabilities from country-specific fixed effect logit models closely track the incidence of financial crises in the United States and United Kingdom over the last century. It is argued that these results reveal an important role for the distribution of accumulated assets in the macro-financial stability of rich countries. The distribution of stocks may capture structural vulnerabilities that the distribution of flows cannot expose, and hence more unequal countries in wealth face greater financial instability. An economic network hypothesis, elaborated in Chapter 2, is proposed for interpreting these results. Chapter 2: Network Defect: Wealth Inequality, Network Topology, and Financial Crisis If two, otherwise identical, economies were distinguished only by their distributions of wealth, are they equally stable in response to a random shock? This essay proposes a theoretical financial network model to understand the relationship between wealth inequality and financial crises. In a financial network, financial assets link individual asset and liability holders to form a web of economic connections. The total connectivity of an individual is de- scribed by their degree, and the overall distribution of connections in the network is imposed through a degree distribution—equivalent to the wealth distribution as incoming connections represent assets and outgoing connections liabilities. A network’s topology varies with the level of wealth inequality and total wealth and together, simulations show, they determine network contagion in the event of a random negative income shock to some individual. Random network simulations, whereby each financial connection is randomly placed, reveal that increasing wealth inequality makes a wealthy network less stable—as measured by the share of individuals failing financially or the decline in financial asset values. These results introduce the idea for a unique topological role for accumulated assets and their distribution in macro-financial stability. Chapter 3: Instability, Credit, and Inequality in the Twentieth Century The final essay studies the long-run relationship between financial instability, wealth inequality and aggregate wealth, and household debt. Specifically, it examines whether wealth inequality and aggregate wealth are contributing forces to the level of financial instability in the United States over the 20th century, or whether debt is a more crucial lever. A more traditional role for income inequality is also investigated and compared, in which its long-run increases may add to household debt and, from there, to a financial crisis. Applying a vector autoregression model, which assumes the endogeneity of the variables, and studying any cointegrating relations provides statistical validity to these relationships through rigorous specification and hypothesis testing. Results show that wealth inequality, acting in concert with the large accumulation of aggregate financial wealth, contributes significantly and positively to financial instability. A second long-run relationship is found between household debt and wealth inequality, whereby increases in financial instability are the main adjusting force back to stationary levels. Less robust evidence is found strongly linking household debt to financial instability, though income inequality does significantly contribute to debt long-term. Together, these results emphasize the important role for the distribution of accumulated wealth in the stability of the US economy

Die Macht der Liebe: Stephan Leopold untersucht die Spannungen zwischen Polis und Eros im Ancien Régime

Stephan Leopold, Liebe im Ancien Régime: ‚eros‘ und ‚polis‘ von Corneille bis Sade (Paderborn: Fink, 2014)

Associations Between C-Reactive Protein, Insulin Sensitivity, and Resting Metabolic Rate in Adults: A Mediator Analysis

Objective: Long-term positive energy balance promotes the development of obesity, a main risk factor for type 2 diabetes mellitus (T2DM). While an association between increased resting metabolic rate (RMR) and insulin sensitivity (IS) was shown previously, the underlying mechanisms remain unclear. Aim of the mediator analysis was to investigate the role of inflammation within the association between RMR and IS.Methods: Anthropometric, clinical, and lifestyle data were collected according to standard operating procedures. RMR was measured using indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as an IS parameter and C-reactive protein (CRP) was measured to represent the inflammatory status. Statistical analyses were performed using SPSS.Results: The analysis included 782 adults (517 females) with a mean age of 32.4 ± 12.0 years and a mean body mass index (BMI) of 24.6 ± 5.2 kg/m2. Regression analysis indicated a significant evidence for associations between RMR and HOMA-IR (ß = 39.3 ± 7.3 kcal/d; p ≤ 0.001) and CRP and HOMA-IR (ß = 0.5 ± 0.1; p ≤ 0.001) after adjustment for fat-free mass, sex, age, and study site. Results of the mediator analysis did not support the hypothesis that CRP is a mediator for the association between RMR and HOMA-IR. These results did not change after participant stratification according to sex or BMI.Conclusion: A significant evidence for an association between RMR and IS was shown in a large cohort. However, the inflammatory status, determined via CRP levels, was not a mediator within this association

Kleinformen von Strukturböden in den Hochlagen des Bayerischen Waldes

Erstmals werden rezente Erdknospen und Texturböden aus den Hochlagen eines deutschen Mittelgebirges beschrieben. Untersuchungen der Form, des Substrats und der Frosteffekte belegen ihre Entstehung als Strukturböden. Im Vordergrund der Untersuchung stehen die heutigen Bedingungen für die Weiterentwicklung und Erhaltung der Form. Dem feuchtigkeitsbedingten Aufquellen des thixotropen Substrats im Sommerhalbjahr und der Bildung von Eiskörnchen an Eistagen kommt eine große morphogenetische Bedeutung für die Kleinformen zu.researc