The flow of bile secretion into the human digestive system was simulated by the dilution of a bile salt-lipid micellar solution. The structural development upon the dilution of the fed state bile model FeSSIF(mod6.5) to the fasted state bile model FaSSIF(mod) was investigated by small-angle neutron scattering (SANS) and dynamic light scattering (DLS) in crossed beam experiments to observe small and large structures in a size range of 1 nm to 50 μm in parallel. Because of the physiologically low lipid and surfactant concentrations of 2.625 mM egg-phosphatidylcholine and 10.5 mM taurocholate the sensitivity of the neutron-structural investigations was improved by partial solvent deuteration with 71% D(2)O, with control experiments in H(2)O. Static experiments of initial and end state systems after 6 days of development revealed the presence of mixed bile salt-lipid micelles of 5.1 nm size in the initial state model FeSSIF(mod6.5), and large liposomes in FaSSIF(mod), which represent the late status after dilution of bile secretion in the intestine in the fasted state. The liposomes depicted a size of 34.39 nm with a membrane thickness of 4.75 nm, which indicates medium to large size unilamellar vesicles. Crossed beam experiments with time-resolved neutron and light scattering experiments after fast mixing with a stopped-flow device revealed a stepwise structural dynamics upon dilution by a factor of 3.5. The liposome formation was almost complete five minutes after bile dilution. The liposomes 30 min after dilution resembled the liposomes found after 6 days and depicted a size of 44.56 nm. In the time regime between 3 and 100 s a kinetic intermediate was observed. In a further experiment the liposome formation was abolished when the dilution was conducted with a surfactant solution containing sodium dodecyl sulfate.

No abstract

No abstract

Transformation of white adipose tissue (WAT) to a brown adipose tissue-like (BAT-like) phenotype has emerged as an attractive approach against obesity e.g. using g ß3 adrenergic receptor agonists. These could however, produce side-effects following systemic exposure. The present study explored the possibility of local use of CL-316,243 - a selective ß3 agonist - to circumvent this problem. Rats treated s.c. for 2 weeks (0.3 and 1 mg/kg) showed decreased inguinal fat pad (IFP) weight/volume, increased UCP-1 staining and expressed BAT-like features in H&E stained micrographs. Interscapular BAT increased in weight/volume. In contrast, local treatment into the IFP was not efficacious in terms of weight/volume, despite slight increases in UCP-1 staining and changes in histological features. After local treatment, the exposure of the IFP was lower than after systemic treatment. In turn higher local doses (0.5 and 5 mg/ml) were then tested which produced a strong trend for decreased volume of the IFP, a significant increase in UCP-1 staining, and also a decrease in adipocytes size but increased number. However, after this treatment the systemic exposure was in the same range as following systemic treatment. In conclusion, we saw no evidence for the possibility of converting inguinal WAT to a BAT-phenotype solely through local activation of ß3 receptors. This is in concert with our in vitro experiments which detected direct effects of PPARγ agonists at the gene/protein expression and functional level, but were unable to detect any effect of CL-316,243.

No abstract