Angiotensin AT1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin.

Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT1 receptor) signaling. Here, we report that losartan, a selective AT1 receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT1 receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The in vivo browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, in vivo apelin knockdown by adeno-associated virus carrying-apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT1 receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders.

CO Sensing Properties of Chemiresistive In2O3/SnO2 Composite Nanoparticle Sensors.

In2O3/SnO2 composite nanoparticles (NPs) were synthesized by a hydrothermal method. Fringes and spotty patterns were observed in high-resolution TEM images and corresponding selected area electron diffraction pattern, respectively, suggesting the nanoparticles were single crystals. X-ray diffraction results revealed that the In2O3/SnO2 composite NP sensor consisted of three phases: In2O3, SnO2 and In2Sn2O7-x (indium tin oxide: ITO). Energy-dispersive X-ray spectrum of the 9:1 In2O3/SnO2 composite NPs showed the atomic ratio of In2O3 to SnO2 was close to 9:1. The response of the chemiresistive sensor to CO was 9.2, which is within the highest 15% among the response values reported for the past 10 years. The ITO NP-based gas sensor is selective toward CO against other reducing gases such as toluene, acetone and benzene. The enhanced response of the 9:1 In2O3/SnO2 composite NP sensor to CO compared to the pure In2O3 NP sensor can be explained mainly by the stronger resistance modulation at the In2O3/SnO2 junctions.

Molecular and biochemical characteristics of ß-propeller phytase from marine Pseudomonas sp. BS10-3 and its potential application for animal feed additives.

Phytate is an antinutritional factor that impacts the bioavailability of essential minerals such as Ca(2+), Mg(2+), Mn(2+), Zn(2+), and Fe(2+) by forming insoluble mineral-phytate salts. These insoluble mineral-phytate salts are hydrolyzed rarely by monogastric animals, because they lack the hydrolyzing phytases and thus excrete the majority of them. The ß-propeller phytases (BPPs) hydrolyze these insoluble mineral-phytate salts efficiently. In this study, we cloned a novel BPP gene from a marine Pseudomonas sp. This Pseudomonas BPP gene (PsBPP) had low sequence identity with other known phytases and contained an extra internal repeat domain (residues 24-279) and a typical BPP domain (residues 280-634) at the C-terminus. Structurebased sequence alignment suggested that the N-terminal repeat domain did not possess the active-site residues, whereas the C-terminal BPP domain contained multiple calcium-binding sites, which provide a favorable electrostatic environment for substrate binding and catalytic activity. Thus, we overexpressed the BPP domain from Pseudomonas sp. to potentially hydrolyze insoluble mineral-phytate salts. Purified recombinant PsBPP required Ca(2+) or Fe(2+) for phytase activity, indicating that PsBPP hydrolyzes insoluble Fe(2+)-phytate or Ca2+-phytate salts. The optimal temperature and pH for the hydrolysis of Ca(2+)-phytate by PsBPP were 50°C and 6.0, respectively. Biochemical and kinetic studies clearly showed that PsBPP efficiently hydrolyzed Ca(2+)-phytate salts and yielded myo-inositol 2,4,6-trisphosphate and three phosphate groups as final products. Finally, we showed that PsBPP was highly effective for hydrolyzing rice bran with high phytate content. Taken together, our results suggest that PsBPP has great potential in the animal feed industry for reducing phytates.