Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3''UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration.     

Production of Particle‐Stabilized Nonspherical Emulsion Drops in Simple Shear Flow

Nonspherical drops are of interest in the formation of microcapsules in life sciences like food, pharmacy, and cosmetics, agro and fine chemicals as well as material sciences. Out of many systems, particle‐stabilized emulsion drops, so‐called Pickering emulsions, exhibit an interesting formulation. Systems with Pickering particles applied in an excess amount were investigated. During deformation, the particles fully covered the enlarged drop interfaces and prevented its relaxation to a spherical drop shape. Nonspherical drops could be produced in simple shear flow using an adequate process routine. The production in a simple device is a promising high‐throughput alternative to microfluidic devices.     

Depth‐Resolved Modulation of Metal–Oxygen Hybridization and Orbital Polarization across Correlated Oxide Interfaces

Interface‐induced modifications of the electronic, magnetic, and lattice degrees of freedom drive an array of novel physical properties in oxide heterostructures. Here, large changes in metal–oxygen band hybridization, as measured in the oxygen ligand hole density, are induced as a result of interfacing two isovalent correlated oxides. Using resonant X‐ray reflectivity, a superlattice of SrFeO₃ and CaFeO₃ is shown to exhibit an electronic character that spatially evolves from strongly O‐like in SrFeO₃ to strongly Fe‐like in CaFeO₃. This alternating degree of Fe electronic character is correlated with a modulation of an Fe 3d orbital polarization, giving rise to an orbital superstructure. At the SrFeO₃/CaFeO₃ interfaces, the ligand hole density and orbital polarization reconstruct in a single unit cell of CaFeO₃, demonstrating how the mismatch in these electronic parameters is accommodated at the interface. These results provide new insight into how the orbital character of electrons is altered by correlated oxide interfaces and lays out a broadly applicable approach for depth‐resolving band hybridization.     

Intake of ruminant versus industrial trans fatty acids and risk of coronary heart disease – what is the evidence?

Several studies have reported a positive association between intake of trans fatty acids and risk of heart disease. It has been suggested that trans fatty acids from ruminant sources are less detrimental than trans fatty acids from industrial sources. Legislation or advice on limiting trans fatty acids has, in some instances, been restricted to trans fatty acids from industrial sources. However, comparisons of ruminant and industrial trans fatty acids have been based on few studies using relative intake data (e.g. quintiles of intakes). Therefore, we have reviewed data describing the associations between absolute intake (g eaten per day) of ruminant and industrial trans fatty acids and risk of coronary heart disease, and examined the associations graphically. Where direct comparison is possible, there are no differences in risk of coronary heart disease between total, ruminant and industrial trans fatty acids for intakes up to 2.5 g/d. At higher intakes (more than 3 g/d) total and industrial trans fatty acids are associated with an increased risk of coronary heart disease but there is insufficient data available on ruminant trans fatty acids at this level of intake. The scarce data do not support discrimination between ruminant and industrial trans fatty acids in dietary recommendations or legislation.     

Biological Evaluation and X‐ray Co‐crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase,an Enzyme from the Redox Metabolism of Trypanosoma

The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure‐based design. The best inhibitors were freely soluble and showed competitive inhibition constants (K_i) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half‐maximal inhibitory concentration, IC₅₀) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X‐ray co‐crystal structures confirmed the binding of the ligands to the hydrophobic wall of the “mepacrine binding site” with the new, solubility‐providing vectors oriented toward the surface of the large active site.     

Textural and ultrastructural changes during processing and storage of lightly preserved salmon (Salmo salar) products

The effect of a controlled lactic fermentation on textural and ultrastructural properties of salmon fillets was evaluated. When compared with a non‐inoculated cured sample, fermented salmon had unique textural properties since it exhibited significantly higher force (p < 0.05) and work (p < 0.001) values in a penetration test on two sampling days but a consistently lower hardness (p < 0.05) in a Texture Profile Analysis (TPA) rheological test. Study of the myofibrillar ultrastructure showed that basic structures were drastically damaged during processing and storage of fermented and cured salmon. Nevertheless, Z‐lines were better preserved in fermented samples. It is suggested that the slight protective effect of lactic fermentation with the starter L sake may be the consequence of a lower pH, by putatively inhibiting neutral or alkaline proteolytic enzymes. © 2000 Society of Chemical Industry     

Nutrient contents,rumen protein degradability and antinutritional factors in some colour- and white-flowering cultivars of Vicia faba beans

Six colour-flowering (Scirocco, Alfred, Carola, Condor, Tina and Herz Freya) and six white-flowering (Caspar, Albatros, Gloria, Tyrol, Vasco and Cresta) cultivars of Vicia faba were studied. The crude protein contents of colour- and white-flowering cultivars were 267±13·6 and 283±18·8 g kg⁻¹, respectively, which did not differ significantly at P<0·05. The levels of lipids, crude fibre, starch and ash varied from 14 to 22 g kg⁻¹, 88 to 143 g kg⁻¹, 407 to 485 g kg⁻¹ and 32 to 42 g kg⁻¹, respectively. The calculated organic matter digestibility (OMD) and metabolisable energy (ME) of the white-flowering cultivars were significantly higher (P<0·001) than those of the colour-flowering cultivars (OMD: 889·1±26·6 g kg⁻¹ vs 797·5±17·1 g kg⁻¹; ME: 13·97±0·49 vs 12·30±0·34 MJ kg⁻¹). In all cultivars, sulphur amino acids were lower than adequate concentration when compared with recommended amino acid pattern of FAO/WHO/UNO reference protein for a 2–5-year-old child. The in vitro rumen nitrogen degradability of colour-flowering cultivars was significantly lower (P<0·01) compared to that of white-flowering cultivars (71·4±9·3% vs 88·0±11·1%). Amongst colour-flowering varieties, the contents of total phenols (TP), tannins (T) and condensed tannins (CT) were highest in Alfred (28·3, 21·0 and 35·4 g kg⁻¹, respectively). The contents of TP and T were similar (about 15 and 10 g kg⁻¹, respectively) in Carola, Tina and Herz Freya, and the CT were in the order: Condor>Herz Freya>Carola. The CT were not detected in white-flowering varieties, T were virtually absent and TP were extremely low (4·0–4·9 g kg⁻¹). The activities of other antinutritional factors (white- and colour-flowering cultivars, respectively: trypsin inhibitor activity 3·05±0·34 and 1·85±0·09 mg trypsin inhibited g⁻¹; lectin 27·2±9·4 and 27·1±5·1 mg ml⁻¹ assay medium producing haemagglutination; phytate 15·0±2·7 and 16·6±2·3 g kg⁻¹) were very low. A strong negative correlation (r=-0·92, P<0·001) between tannins and in vitro rumen protein degradability was observed which suggested that tannins have adverse effect on protein degradability. Similarly negative correlations between tannin levels and metabolisable energy (r=-0·89; P<0·001) and organic matter digestibility (r=-0·89; P<0·001) were observed. The correlation coefficient between trypsin inhibitor activity and tannins was negative and highly significant (r=-0·88, P<0·001), whereas between tannins and saponins it was significantly positive (r=0·96, P<0·001). ©1997 SCI     

6‐Dihydroparadol,a Ginger Constituent,Enhances Cholesterol Efflux from THP‐1‐Derived Macrophages

1 Scope

Ginger is reported to be used for the prevention and treatment of cardiovascular diseases (CVD). Cholesterol efflux from macrophage foam cells is an important process in reverse cholesterol transport, whose increase may help to prevent or treat CVD. In this study, we investigated the effects of 6‐dihydroparadol from ginger on macrophage cholesterol efflux.

2 Methods and results

We show that 6‐dihydroparadol concentration‐dependently enhances both apolipoprotein A1‐ and human plasma–mediated cholesterol efflux from cholesterol‐loaded THP‐1‐derived macrophages using macrophage cholesterol efflux assay. 6‐Dihydroparadol increases protein levels of both ATP‐binding cassette transporters A1 and G1 (ATP‐binding cassette transporter A1 [ABCA1] and ATP‐binding cassette transporter G1 [ABCG1]) according to Western blot analysis. The ABCA1 inhibitor probucol completely abolishes 6‐dihydroparadol‐enhanced cholesterol efflux. Furthermore, increased ABCA1 protein levels in the presence of 6‐dihydroparadol were associated with both increased ABCA1 mRNA levels and increased ABCA1 protein stability. Enhanced ABCG1 protein levels were only associated with increased protein stability. Increased ABCA1 protein stability appeared to be the result of a reduced proteasomal degradation of the transporter in the presence of 6‐dihydroparadol.

3 Conclusion

We identified 6‐dihydroparadol from ginger as a novel promoter of cholesterol efflux from macrophages that increases both ABCA1 and ABCG1 protein abundance. This newly identified bioactivity might contribute to the antiatherogenic effects of ginger.