Fatp4 exhibits acyl-CoA synthetase activity and is thereby able to catalyze the activation of fatty acids for further metabolism. However, its actual function in most tissues remains unresolved, and its role in cellular fatty acid uptake is still controversial. To characterize Fatp4 functions in adipocytes in vivo, we generated a mouse line with adipocyte-specific inactivation of the Fatp4 gene (Fatp4 A؊/؊ ). Under standard conditions mutant mice showed no phenotypical aberrance. Uptake of radiolabeled palmitic and lignoceric acid into adipose tissue of Fatp4 A؊/؊ mice was unchanged. When exposed to a diet enriched in long chain fatty acids, Fatp4 A؊/؊ mice gained more body weight compared with control mice, although they were not consuming more food. Pronounced obesity was accompanied by a thicker layer of subcutaneous fat and greater adipocyte circumference, although expression of genes involved in de novo lipogenesis was not changed. However, the increase in total fat mass was contrasted by a significant decrease in various phospholipids, sphingomyelin, and cholesteryl esters in adipocytes. Livers of Fatp4-deficient animals under a high fat diet exhibited a higher degree of fatty degeneration. Nonetheless, no evidence for changes in insulin sensitivity and adipose inflammation was found. In summary, the results of this study confirm that Fatp4 is not crucial for fatty acid uptake into adipocytes. Instead, under the condition of a diet enriched in long chain fatty acids, adipocyte-specific Fatp4 deficiency results in adipose hypertrophy and profound alterations in the metabolism of complex lipids.The mechanism of fatty acid uptake into the cell is still under debate. In recent years there has been growing evidence for fatty acid uptake across the plasma membrane by specific protein transport systems rather than by mere diffusion processes (1). In line with this perception, there has been increasing interest in an evolutionarily conserved group of genes encoding fatty acid transport proteins (Fatps). 4 The Fatp family consists of six members (Fatp1-6) of which Fatp1 was first described and is the best characterized (2). A 60% homologue to that founding member of the Fatp family is Fatp4. Like other members of this gene family, it shows a tissue-specific expression pattern. It can be detected in skin, liver, adipose tissue, brain, skeletal muscle, and heart and is the only Fatp found in small intestine (3). For most of these tissues, the physiological function of Fatp4 is unknown. In several experiments, overexpression of Fatp4 in different cultured cell lines resulted in an increased cellular influx of fatty acids (4 -7). In line with these observations, Fatp4 was initially presumed to be a typical transmembrane transport protein (4). Meanwhile, there is emerging evidence that Fatp4 is not plasma membrane-associated but is localized to the endoplasmic reticulum (8) or other intracellular compartments (5, 9). Furthermore, like other members of the gene family, Fatp4 exhibits acyl-CoA synthetase activity and is t...

A new version release (4.0) of the molecular simulation tool ms2 (Deublein et al., 2011; is presented. Version 4.0 of ms2 features two additional potential functions to address the repulsive and dispersive interactions in a more versatile way, i.e. the Mie potential and the Tang-Toennies potential. This version further introduces Kirkwood-Buff integrals based on radial distribution functions, which allow the sampling of the thermodynamic factor of mixtures with up to four components, orientational distribution functions to elucidate mutual configurations of neighboring molecules, thermal diffusion coefficients of binary mixtures for heat, mass as well as coupled heat and mass transport, Einstein relations to sample transport properties with an alternative to the Green-Kubo formalism, dielectric constant of non-polarizable fluid models, vapor-liquid equilibria relying on the second virial coefficient and cluster criteria to identify nucleation.

The relative permittivity is a property that depends on the orientation structure of a fluid. Thus, using state-of-the-art equations of state it can be modeled only when using high level techniques, such as nonprimitive models. This is a drawback, especially when electrolytes are present: when using a primitive model, an auxiliary model for the relative permittivity must be introduced. Here, we pursue a different approach to predict the relative permittivity. The recently developed 'Co-Oriented Fluid Functional Equation for Electrostatic Interactions' (COFFEE) framework considers the mutual orientation of molecular dipole moments. It thereby enables a prediction of the relative permittivity when combined with Kirkwood's theory. To assess these predictions obtained from COFFEE, we present a comprehensive set of molecular simulation data for the relative permittivity of Stockmayer-type model fluids at wide ranges of temperature and density. Continuing a previous work, we extend the range of states considered to the homogeneous vapor, liquid, and supercritical regions. We find that when plotting the relative permittivity as a function of the ratio of density and temperature, all data points for a certain fluid collapse onto a single master curve. To a good approximation, the same holds for experimental data of the relative permittivity of water. By comparing the molecular simulation results with COFFEE, a good overall agreement is observed. Both data sets follow the same qualitative trends. Also reasonable quantitative agreement is found for many state points, the only exception being dense states at low temperatures.

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Objective: The effect of enoxaparin and fibroblast growth factor-1 (FGF-1) on post-infarction capillary density and regional myocardial blood flow (RMBF) was examined. Methods: New Zealand White rabbits received an intramyocardial injection of either physiological saline, FGF-1 + enoxaparin, FGF-1 or enoxaparin directly after ligation of the left anterior descending artery. RMBF and capillary density were investigated using fluorescent microspheres and histological examination. Results: One week after infarction a significant difference in the number of capillaries could be demonstrated within the FGF-1 + enoxaparin group (p < 0.001 versus the control group), the FGF-1 group (p < 0.01) and the enoxaparin group (p < 0.05). Treatment with FGF-1 + enoxaparin resulted in a significantly increased number of capillaries compared to treatment with FGF-1 (p < 0.05) and enoxaparin (p < 0.05) alone. Additionally, all groups treated with FGF-1 and/or enoxaparin showed a significant increase of microvessel density in the treated ischemic border zone compared to the non-treated ischemic border zone (p < 0.001 for FGF-1 + enoxaparin, p < 0.01 for FGF-1, p < 0.05 for enoxaparin). RMBF was significantly increased within the FGF-1 + enoxaparin group compared to the control group (p < 0.05). Moreover, perfusion rates within the FGF-1 + enoxaparin-treated area did not significantly differ from the pre-infarction values. Conclusion: Treatment with either enoxaparin or FGF-1 or FGF-1 + enoxaparin resulted in increased microvessel growth. However, only the combination of enoxaparin with FGF-1 promotes capillary growth and RMBF. Thus, we conclude that enoxaparin enhances the angiogenic potential of intramyocardially injected FGF-1 in the acutely infarcted rabbit heart.