A novel esterase, PpEst, that hydrolyses the co-aromatic-aliphatic polyester poly(1,4-butylene adipate-co-terephthalate) (PBAT) was identified by proteomic screening of the Pseudomonas pseudoalcaligenes secretome. PpEst was induced by the presence of PBAT in the growth media and had predicted arylesterase (EC 3.1.1.2) activity. PpEst showed polyesterase activity on both whole and milled PBAT film releasing terephthalic acid and 4-(4-hydroxybutoxycarbonyl)benzoic acid while end product inhibition by 4-(4-hydroxybutoxycarbonyl)benzoic acid was observed. Modelling of an aromatic polyester mimicking oligomer into the PpEst active site indicated that the binding pocket could be big enough to accommodate large polymers. This is the first report of a PBAT degrading enzyme being identified by proteomic screening and shows that this approach can contribute to the discovery of new polymer hydrolysing enzymes. Moreover, these results indicate that arylesterases could be an interesting enzyme class for identifications of polyesterases.

Histone deacetylase inhibition counteracts adverse left ventricular remodeling, improves pulmonary function, and reverses diastolic dysfunction.

Although the epidemiology of high-density lipoprotein (HDL) cholesterol and cardiovascular risk has been consistent, pharmacologic interventions to increase HDL-cholesterol by delaying HDL catabolism did not translate into reduction in cardiovascular risk. HDL particles are small, protein-rich when compared to other plasma lipoprotein classes. Latest progresses in proteomics technology have dramatically increased our understanding of proteins carried by HDL. In addition to proteins with well-established functions in lipid transport, iron transport proteins, members of the complement pathway, and proteins involved in immune function and acute phase response were repeatedly identified on HDL particles. With the unraveling of the complexity of the HDL proteome, different laboratories have started to monitor its changes in various disease states. In addition, dynamic aspects of HDL subgroups are being discovered. These recent studies clearly illustrate the promise of HDL proteomics for deriving new biomarkers for disease diagnosis and to measure the effectiveness of current and future treatment regimens. This review summarizes recent advances in proteomics and lipidomics helping to understand HDL function in health and disease.

Anita Sahu-Osen, Gabriela Montero-Moran, Matthias Schittmayer, Katarina Fritz, Anna Dinh, Yu-Fang Chang, Derek McMahon, Andras Boeszoermenyi, Irina Cornaciu, Deanna Russell, Monika Oberer, George M. Carman, Ruth Birner-Gruenberger, Dawn L. Brasaemle

Histone acetylation depends on the abundance of nucleo-cytoplasmic acetyl-CoA. Here, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. N-acetylaspartate (NAA) is a highly abundant brain metabolite catabolized by aspartoacylase yielding aspartate and acetate. The latter can be further used for acetyl-CoA production. Prior to this work, the presence of NAA has not been described in adipocytes. Here, we show that accumulation of NAA decreases the brown adipocyte phenotype. We increased intracellular NAA concentrations in brown adipocytes via media supplementation or knock-down of aspartoacylase and measured reduced lipolysis, thermogenic gene expression and oxygen consumption. Combinations of approaches to increase intracellular NAA levels showed additive effects on lipolysis and gene repression, nearly abolishing the expression of Ucp1, Cidea, Prdm16 and Ppara. Transcriptome analyses of aspartoacylase knock-down cells indicate deficiencies in acetyl-CoA and lipid metabolism. Concordantly, cytoplasmic acetyl-CoA levels and global histone H3 acetylation were decreased. Further, activating histone marks (H3K27ac and H3K9ac) in promoters/enhancers of brown marker genes showed reduced acetylation status. Taken together, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. Thereby, we mechanistically connect the NAA pathway to the epigenomic regulation of gene expression, modulating the phenotype of brown adipocytes.