Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism.

We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression during cold exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are increased; and 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4. In summary, our results demonstrate extensive and diverse gene expression changes related to glucose handling in activated BAT.

Intermodal and cross-polarization four-wave mixing in large-core hybrid photonic crystal fibers.

Degenerate four-wave mixing is considered in large mode area hybrid photonic crystal fibers, combining photonic bandgap guidance and index guidance. Co- and orthogonally polarized pump, signal and idler fields are considered numerically by calculating the parametric gain and experimentally by spontaneous degenerate four-wave mixing. Intermodal and birefringence assisted intramodal phase matching is observed. Good agreement between calculations and experimental observations is obtained. Intermodal four-wave mixing is achieved experimentally with a conversion efficiency of 17%.

Polarization switch of four-wave mixing in large mode area hybrid photonic crystal fibers.

Degenerate spontaneous four-wave mixing is considered in a large mode area hybrid photonic crystal fiber. Numerical and experimental results show birefringence assisted four-wave mixing for a certain polarization state of the pump field. The parametric gain can be turned on and off by switching the polarization state of the pump field between the two principal axis of the hybrid photonic crystal fiber.

Large-mode-area hybrid photonic crystal fiber amplifier at 1178 nm.

Amplification of 1178 nm light is demonstrated in a large-mode-area single-mode ytterbium-doped hybrid photonic crystal fiber, relying on distributed spectral filtering of spontaneous emission at shorter wavelengths. An output power of 53 W is achieved with 29 dB suppression of parasitic lasing. Further power scaling is limited by parasitic lasing.

Extended parametric gain range in photonic crystal fibers with strongly frequency-dependent field distributions.

The parametric gain range of a degenerate four-wave mixing process is determined in the undepleted pump regime. The gain range is considered with and without taking the mode field distributions of the four-wave mixing components into account. It is found that the mode field distributions have to be included to evaluate the parametric gain correctly in dispersion-tailored speciality fibers and that mode profile engineering can provide a way to increase the parametric gain range.

Degenerate four wave mixing in large mode area hybrid photonic crystal fibers.

Spontaneous degenerate four wave mixing (FWM) is investigated in large mode area hybrid photonic crystal fibers, in which photonic bandgap guidance and index guidance is combined. Calculations show the parametric gain is maximum on the edge of a photonic bandgap, for a large range of pump wavelengths. The FWM products are observed on the edges of a transmission band experimentally, in good agreement with the numerical results. Thereby the bandedges can be used to control the spectral positions of FWM products through a proper fiber design. The parametric gain control combined with a large mode area fiber design potentially allows for power scaling of light at wavelengths not easily accessible with e.g. rare earth ions.

Optimizing single mode robustness of the distributed modal filtering rod fiber amplifier.

High-power fiber amplifiers for pulsed applications require large mode area (LMA) fibers having high pump absorption and near diffraction limited output. Photonic crystal fibers allow realization of short LMA fiber amplifiers having high pump absorption through a pump cladding that is decoupled from the outer fiber diameter. However, achieving ultra low NA for single mode (SM) guidance is challenging, thus different design strategies must be applied. The distributed modal filtering (DMF) design enables SM guidance in ultra low NA fibers with very large cores, where large preform tolerances can be compensated during the fiber draw. Design optimization of the SM bandwidth of the DMF rod fiber is presented. Analysis of band gap properties results in a fourfold increase of the SM bandwidth compared to previous results, achieved by utilizing the first band of cladding modes, which can cover a large fraction of the Yb emission band including wavelengths of 1030 nm and 1064 nm. Design parameters tolerating refractive index fabrication uncertainties of ± 10⁻4 are targeted to yield stable SM bandwidths.

Hybrid Ytterbium-doped large-mode-area photonic crystal fiber amplifier for long wavelengths.

A large-mode-area Ytterbium-doped photonic crystal fiber amplifier with build-in gain shaping is presented. The fiber cladding consists of a hexagonal lattice of air holes, where three rows are replaced with circular high-index inclusions. Seven missing air holes define the large-mode-area core. Light confinement is achieved by combined index and bandgap guiding, which allows for single-mode operation and gain shaping through distributed spectral filtering of amplified spontaneous emission. The fiber properties are ideal for amplification in the long wavelength regime of the Ytterbium gain spectrum above 1100 nm, and red shifting of the maximum gain to 1130 nm is demonstrated.

Activation of PPARgamma by metabolites from the flowers of purple coneflower (Echinacea purpurea).

Thiazolidinediones are insulin sensitizing drugs that target the peroxisome proliferator-activated receptor (PPAR) gamma. An n-hexane extract of the flowers of Echinacea purpurea was found to activate PPARgamma without stimulating adipocyte differentiation. Bioassay-guided fractionations yielded five alkamides, of which one was new, and three fatty acids that all activated PPARgamma. The new alkamide hexadeca-2E,9Z,12Z,14E-tetraenoic acid isobutylamide (5) was identified by analysis of spectroscopic data and found to activate PPARgamma with no concurrent stimulation of adipocyte differentiation. Compound 5 was further shown to increase insulin-stimulated glucose uptake. The data suggest that flowers of E. purpurea contain compounds with potential to manage insulin resistance and type 2 diabetes.

Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice.

Cyclooxygenases are known as important regulators of metabolism and immune processes via conversion of C20 fatty acids into various regulatory lipid mediators, and cyclooxygenase activity has been implicated in browning of white adipose tissues. We generated transgenic (TG) C57BL/6 mice expressing the Ptgs2 gene encoding cyclooxygenase-2 (COX-2) in mature adipocytes. TG mice fed a high-fat diet displayed marginally lower weight gain with less hepatic steatosis and a slight improvement in insulin sensitivity, but no difference in glucose tolerance. Compared to littermate wildtype mice, TG mice selectively reduced inguinal white adipose tissue (iWAT) mass and fat cell size, whereas the epididymal (eWAT) fat depot remained unchanged. The changes in iWAT were accompanied by increased levels of specific COX-derived lipid mediators and increased mRNA levels of interleukin-33, interleukin-4 and arginase-1, but not increased expression of uncoupling protein 1 or increased energy expenditure. Epididymal WAT (eWAT) in TG mice exhibited few changes except from increased infiltration with eosinophils. Our findings suggest a role for COX-2-derived lipid mediators from adipocytes in mediating type 2 immunity cues in subcutaneous WAT associated with decreased hepatic steatosis, but with no accompanying induction of browning and increased energy expenditure.