Obesity resistant mechanisms in the Lean polygenic mouse model as indicated by liver transcriptome and expression of selected genes in skeletal muscle

<p>Abstract</p> <p>Background</p> <p>Divergently selected Lean and Fat mouse lines represent unique models for a polygenic form of resistance and susceptibility to obesity development. Previous research on these lines focused mainly on obesity-susceptible factors in the Fat line. This study aimed to examine the molecular basis of obesity-resistant mechanisms in the Lean line by analyzing various fat depots and organs, the liver transcriptome of selected metabolic pathways, plasma and lipid homeostasis and expression of selected skeletal muscle genes.</p> <p>Results</p> <p>Expression profiling using our custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol biosynthesis genes compared to the Fat line, although this was not reflected in elevation of total plasma or liver cholesterol. However, FPLC analysis showed that protective HDL cholesterol was elevated in Lean mice. A significant difference between the strains was also found in bile acid metabolism. Lean mice had a higher expression of <it>Cyp8b1</it>, a regulatory enzyme of bile acid synthesis, and the <it>Abcb11 </it>bile acid transporter gene responsible for export of acids to the bile. Additionally, a higher content of blood circulating bile acids was observed in Lean mice. Elevated HDL and upregulation of some bile acids synthesis and transport genes suggests enhanced reverse cholesterol transport in the Lean line - the flux of cholesterol out of the body is higher which is compensated by upregulation of endogenous cholesterol biosynthesis. Increased skeletal muscle <it>Il6 </it>and <it>Dio2 </it>mRNA levels as well as increased activity of muscle succinic acid dehydrogenase (SDH) in the Lean mice demonstrates for the first time that changes in muscle energy metabolism play important role in the Lean line phenotype determination and corroborate our previous findings of increased physical activity and thermogenesis in this line. Finally, differential expression of <it>Abcb11 </it>and <it>Dio2 </it>identifies novel strong positional candidate genes as they map within the quantitative trait loci (QTL) regions detected previously in crosses between the Lean and Fat mice.</p> <p>Conclusion</p> <p>We identified novel candidate molecular targets and metabolic changes which can at least in part explain resistance to obesity development in the Lean line. The major difference between the Lean and Fat mice was in increased liver cholesterol biosynthesis gene mRNA expression, bile acid metabolism and changes in selected muscle genes' expression in the Lean line. The liver <it>Abcb11 </it>and muscle <it>Dio2 </it>were identified as novel positional candidate genes to explain part of the phenotypic difference between the Lean and Fat lines.</p

Melt Spinning of Fibers: Effect of Air Drag

Experimental measurements of the magnitude of air drag on the filament and the air velocity profile around the filament in the spinning and drawing down of a fiber filament in the surrounding of stagnant air are reported. The results are examined in comparison with the existing theoretical correlations which have been used in the studies of the spinning processes. The experimental values of the air drag are found to be larger than the values based on the existing correlations to such an extent that, in some cases of past studies, the air drag effect on the filament tension may have been underestimated.</jats:p

Endurance of Polymeric Fibers in Cyclic Tension

Abstract The performance characteristics of simple filaments in fatigue in cyclic longitudinal tension are reviewed and discussed in terms of a theory which assumes that the fracture is a result of the formation of an unstable crack. It is shown that the derived relationships are in qualitative agreement with observed effects of temperature, frequency, stroke, etc. In quantitative studies however, and especially with those intended to extract values of unknown parameters, it must be observed that the derived expressions apply only for the conditions where the effects of structural reorganization in front of the propagating crack are negligible in comparison with the effects associated in the formation of new crack surfaces. Thus, the theory is applicable primarily to highly oriented fibers which are ruptured at temperatures below Tg. In the analysis of the results of the fatigue experiments, it is also necessary to take into account the structural changes which take place during the initial period of loading (mechanical conditioning). In this period the fibers change considerably in their properties (modulus, elongation at break, etc.) which in turn affects the fatiguing conditions. In the interpretation of data obtained in fatiguing at constant stress or strain amplitude, it must be observed that the theory also indicates that the severity of fatiguing conditions should be expressed in terms of strain-energy amplitude instead of the commonly used stress- or strain-amplitude arguments. This analysis is based on the appearance of the term σ2/E=σε in the expressions for lifetime. It is conceivable that our experimental data discussed in Experimental (fourth subsection) would not show the large difference between fatiguing at constant stroke and constant force-amplitude, if the results of both experiments were plotted as a function of σ∈. The most important goal of our study was to establish a method for predicting the potential endurance of fibers from their molecular structure. The derived equations include the three primary parameters which are affected by the molecular structure of the polymers: fracture surface energy, modulus, and activation energy associated with the processes involved in crack growth. The physical significance of these factors is discussed and methods to estimate their numerical values from known molecular parameters are reviewed. In correlating or predicting the fatigue behavior from molecular structure of the polymer, it must be remembered that the derived expressions hold for a perfectly oriented, flawless ensemble of molecules. The studies of fiber morphology on the other hand, show that the fibers consist of at least two phases differing primarily in the degree of order. Since the studies of mechanical coupling between phases indicate a poor load transfer between phases it is obvious that the morphological characteristics (e.g., chain folding) play a very important role in the overall mechanical behavior of the fibers and, therefore, must be considered. The studies of the effects of morphology on mechanical properties of fibers are still in an early stage of development. Further work is required to elucidate the fiber morphology and especially the structure of the phase boundary (crystal surfaces, concentration of tie-molecules, etc.). Developments are also necessary in a theory which would adequately describe the mechanical responses of such complex systems. If one considers that the strength of present “high tenacity” fibers is about 5–10 times lower than calculated values, assuming a flawless structure, then it is expected that functional modifications of fiber morphology should lead to significant increases in their strength, endurance, and modulus.</jats:p

Role of Adhesion in Viscoelastic Properties of Rubber-Tire Cord Composites

Abstract Dynamic mechanical measurements have been carried out on samples of rubber and PET cord-rubber composites, with and without adhesive, as a function of strain amplitude, temperature, pretension, angle of strain application and time of cycling. The results show that mechanical loss and dynamic modulus depend on these variables as well as the presence and type of adhesive at the cord-rubber interface. Based on these results, we conclude that adhesion plays a significant role in the viscoelastic properties of a composite and it is an important factor along with the properties of components in the analysis of tire performance in terms of composite properties. This study clearly shows that the maximum adhesion may not be the optimum adhesion in tire technology. The most relevant question, i.e., the determination of the optimum level of adhesion for a specific tire, however, remains unanswered. The viscoelastic properties of the composites decrease with time of cycling but the rate of decrease depends upon the level of adhesion in the starting material. This result could be important in the development of a more realistic dynamic adhesion test. Attempts to use the viscoelastic experiments with small amplitude, high frequency strain to determine the onset of fracture in the composite specimen appears to be promising. Work is in progress to determine the potential of this method in the analysis of adhesion.</jats:p