Perilipin 2 (PLIN2) is a lipid-droplet protein that is up-regulated in alcoholic steatosis and associated with hepatic accumulation of ceramides, bioactive lipids implicated in alcoholic liver disease pathogenesis. The specific role of ceramide synthetic enzymes in the regulation of PLIN2 and promotion of hepatocellular lipid accumulation is not well understood. We examined the effects of pharmacologic ceramide synthesis inhibition on hepatic PLIN2 expression, steatosis, and glucose and lipid homeostasis in mice with alcoholic steatosis and in ethanol-incubated human hepatoma VL17A cells. In cells, pharmacologic inhibition of ceramide synthase reduced lipid accumulation by reducing PLIN2 RNA stability. The subtype ceramide synthase (CerS)6 was specifically up-regulated in experimental alcoholic steatosis and and was up-regulated in zone 3 hepatocytes in human alcoholic steatosis. ceramide reduction by inhibition of ceramide synthesis reduced PLIN2 and hepatic steatosis in alcohol-fed mice, but only synthesis inhibition, not sphingomyelin hydrolysis, improved glucose tolerance and dyslipidemia. These findings implicate CerS6 as a novel regulator of PLIN2 and suggest that ceramide synthetic enzymes may promote the earliest stage of alcoholic liver disease, alcoholic steatosis.-Williams, B., Correnti, J., Oranu, A., Lin, A., Scott, V., Annoh, M., Beck, J., Furth, E., Mitchell, V., Senkal, C. E., Obeid, L., Carr, R. M. A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.

A regional long-offset 2D seismic reflection program undertaken along the Labrador margin of the Labrador Sea, Canada, and complemented by the acquisition of coincident gravity data, has provided an extensive data set with which to image and model the sparsely investigated outer shelf, slope, and deepwater regions. Previous interpretation of the seismic data revealed the extent of Mesozoic and Cenozoic basins and resulted in the remapping of the basin configuration for the entire margin. To map the synrift package and improve understanding of the geometry and extent of these basins, we have undertaken joint seismic interpretation and gravity forward modeling to reduce uncertainty in the identification of the prerift basement, which varies between Paleozoic shelfal deposits and Precambrian crystalline rocks, with similar density characteristics. With this iterative approach, we have obtained new depth to basement constraints and have deduced further constraints on crustal thickness variations along the Labrador margin. At the crustal scale, extreme localized crustal thinning has been revealed along the southern and central portions of the Labrador margin, whereas a broad, margin-parallel zone of thicker crust has been detected outboard of the continental shelf along the northern Labrador margin. Our final gravity models suggest that Late Cretaceous rift packages from further south extend along the entire Labrador margin and open the possibility of a Late Cretaceous source rock fairway extending into the Labrador basins.

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Starting in 2011, a multiyear modern 2D long offset broadband seismic survey was acquired offshore Labrador, Canada, by TGS and PGS in partnership with Nalcor Energy. This regional survey covers the slope and deepwater portions of the margin. Three Mesozoic and Cenozoic-aged basins were informally defined from these data, the Chidley, Henley, and Holton; also, the poorly constrained Hawke Basin was remapped. The 2D data set imaged for the first time a very large Cenozoic-aged delta adjacent to the mouth of Lake Melville. We have mapped this delta on a [Formula: see text] 2D seismic grid. The delta is 5–8 km thick, and its aerial extent is [Formula: see text]. The age of this delta has been interpreted to be Eocene to Miocene. Adjacent to this Cenozoic delta on the Labrador shelf, there is a working petroleum system within the proximal Hopedale and Saglek Basins where there are five gas discoveries and one oil discovery. The modern long-offset 2D data set appears to indicate a working petroleum system within the newly mapped Cenozoic delta, and two phases of hydrocarbons may be present.