Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod.

Lipid metabolism is essential in maintaining energy homeostasis in multicellular organisms. In vertebrates, the peroxisome proliferator-activated receptors (PPARs, NR1C) regulate the expression of many genes involved in these processes. Atlantic cod (Gadus morhua) is an important fish species in the North Atlantic ecosystem and in human nutrition, with a highly fatty liver. Here we study the involvement of Atlantic cod Ppar a and b subtypes in systemic regulation of lipid metabolism using two model agonists after in vivo exposure. WY-14,643, a specific PPARA ligand in mammals, activated cod Ppara1 and Ppara2 in vitro. In vivo, WY-14,643 caused a shift in lipid transport both at transcriptional and translational level in cod. However, WY-14,643 induced fewer genes in the fatty acid beta-oxidation pathway compared to that observed in rodents. Although GW501516 serves as a specific PPARB/D ligand in mammals, this compound activated cod Ppara1 and Ppara2 as well as Pparb in vitro. In vivo, it further induced transcription of Ppar target genes and caused changes in lipid composition of liver and plasma. The integrative approach provide a foundation for understanding how Ppars are engaged in regulating lipid metabolism in Atlantic cod physiology. We have shown that WY-14,643 and GW501516 activate Atlantic cod Ppara and Pparb, affect genes in lipid metabolism pathways, and induce changes in the lipid composition in plasma and liver microsomal membranes. Particularly, the combined transcriptomic, proteomics and lipidomics analyses revealed that effects of WY-14,643 on lipid metabolism are similar to what is known in mammalian studies, suggesting conservation of Ppara functions in mediating lipid metabolic processes in fish. The alterations in the lipid profiles observed after Ppar agonist exposure suggest that other chemicals with similar Ppar receptor affinities may cause disturbances in the lipid regulation of fish. Model organism: Atlantic cod (Gadus morhua). LSID: urn:lsid:zoobank.org:act:389BE401-2718-4CF2-BBAE-2E13A97A5E7B. COL Identifier: 6K72F.

Precision cut tissue slices to investigate the effects of triclosan exposure in Mytilus galloprovincialis.

Precision-cut tissue slices (PCTS) are frequently used in mammalian research, but its application in the area of aquatic toxicology is still humble. This work proposes the use of PCTS to investigate the effects of the antimicrobial triclosan (TCS) in the mussel Mytilus galloprovincialis. PCTS sectioned from the digestive gland (400 µm) were exposed to 10, 100, and 500 nM TCS for 24 h, and the expression of selected genes, together with the biomarkers, carboxylesterases (CbE) and glutathione S-transferases (GST), and the analysis of lipids in PCTS and culture medium, were used to investigate the molecular initiating events of triclosan in the digestive gland of mussels. Significant dysregulation in the expression of phenylalanine-4-hydroxylase (PAH), glutamate dehydrogenase (GDH), fatty acid synthase (FASN), and 7-dehydrocholesterol reductase (DHCR7), involved in energy, phenylalanine and lipid metabolism, were detected. The analysis of lipids evidenced significant changes in cholesteryl esters (CEs) and membrane lipids in the culture medium of exposed PCTS, suggesting dysregulation of energy and lipid metabolism that can affect lipid dynamics in mussels exposed to triclosan.

Proteomics and lipidomics analyses reveal modulation of lipid metabolism by perfluoroalkyl substances in liver of Atlantic cod (Gadus morhua).

The aim of the present study was to investigate effects of defined mixtures of polycyclic aromatic hydrocarbons (PAHs) and perfluoroalkyl substances (PFASs), at low, environmentally relevant (1× = L), or high (20× = H) doses, on biological responses in Atlantic cod (Gadus morhua). To this end, farmed juvenile cod were exposed at day 0 and day 7 via intraperitoneal (i.p.) injections, in a two-week in vivo experiment. In total, there were 10 groups of fish (n = 21-22): two control groups, four separate exposure groups of PAH and PFAS mixtures (L, H), and four groups combining PAH and PFAS mixtures (L/L, H/L, L/H, H/H). Body burden analyses confirmed a dose-dependent accumulation of PFASs in cod liver and PAH metabolites in bile. The hepatosomatic index (HSI) was significantly reduced for three of the combined PAH/PFAS exposure groups (L-PAH/H-PFAS, H-PAH/L-PFAS, H-PAH/H-PFAS). Analysis of the hepatic proteome identified that pathways related to lipid degradation were significantly affected by PFAS exposure, including upregulation of enzymes in fatty acid degradation pathways, such as fatty acid ß-oxidation. The increased abundances of enzymes in lipid catabolic pathways paralleled with decreasing levels of triacylglycerols (TGs) in the H-PFAS exposure group, suggest that PFAS increase lipid catabolism in Atlantic cod. Markers of oxidative stress, including catalase and glutathione S-transferase activities were also induced by PFAS exposure. Only minor and non-significant differences between exposure groups and control were found for cyp1a and acox1 gene expressions, vitellogenin concentrations in plasma, Cyp1a protein synthesis and DNA fragmentation. In summary, our combined proteomics and lipidomics analyses indicate that PFAS may disrupt lipid homeostasis in Atlantic cod.

Partial characterization of the lipidome of the cold-water scallop, Chlamys islandica.

Fingerprinting of the main lipid components of the digestive gland of the Icelandic scallop-Chlamys islandica-has been performed by ultra-high-performance liquid chromatography coupled with time of flight high-resolution mass spectrometry, UHPLC-HRMS/ToF. This method allowed the identification of 224 lipids, including phosphatidylcholines (PC), plasmanyl (PC-O)/plasmenyl (PC-P) phosphatidylcholines, lyso-phosphatidylcholines (LPC), and their plasmanyl/plasmenyl forms (LPC-O/LPC-P). Diacylglycerols (DG), triacylglycerols (TG), and cholesteryl esters (CE) were the neutral lipids (NL) analyzed. While all of the lipids showed a strong seasonal dependence in terms of quantity, only NLs presented significant qualitative changes. Principal component analysis (PCA) of TG and DG profiles evidenced a prevalence of low unsaturated TGs and DGs in spring, which were replaced by species with a higher degree of unsaturations in summer. In autumn, long and highly unsaturated TGs constitute the lipid fraction of the digestive gland of the scallop, while DG species offer a mixed profile. This study contributes to the characterization and the elucidation of the lipidome of Chlamys islandica and provides baseline data for further study of the effects of pollutants on the lipidome of the Icelandic scallop, often used as a sentinel species in biomonitoring programs.

Formation of a stable biradical triplet state cation versus a closed shell singlet state cation by oxidation of adducts of 3,6-dimethoxycarbazole and polychlorotriphenylmethyl radicals.

We report an experimental and theoretical study of two stable radical adducts of the triphenylmethyl series, 1 and 2, whose composition and molecular structure are distinguished by the content and position of chlorine atoms in phenyls. The electrochemical study through cyclic voltammetry of these open layer species shows the existence of two reversible processes, related to reduction and oxidation, to stable charged species. The chemical oxidation of both radical adducts gives rise to stable cations, whose fundamental state has a biradical triplet electronic structure or a closed shell singlet character, depending on the electronic conjugation between the donor and acceptor electron moieties. The presence of chlorines adjacent to the nitrogen in 1 breaks the conjugation between both halves, facilitating the formation of a triplet electronic state of the cation, while the absence of chlorines in these positions in 2 facilitates partial conjugation and stabilizes the closed shell singlet electronic state of the cation.