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Background: The first stage of alcoholic liver disease is hepatic steatosis. While alcohol is known to profoundly impact hepatic lipid metabolism, gaps in our knowledge remain regarding the mechanisms leading to alcohol‐induced hepatic triglyceride (TG) accumulation. As the sole enzymes catalyzing the final step in TG synthesis, diacylglycerol O‐acyltransferase (DGAT) 1 and 2 are potentially important contributors to alcoholic steatosis. Our goal was to study the effects of dietary fat content on alcohol‐induced hepatic TG accumulation, and the relative contribution of DGAT1 and DGAT2 to alcoholic steatosis. Methods: These studies were carried out in wild‐type (WT) mice fed alcohol‐containing high‐fat or low‐fat formulations of Lieber‐DeCarli liquid diets, as well as follow‐up studies in Dgat1−/− mice. Results: A direct comparison of the low‐fat and high‐fat liquid diet in WT mice revealed surprisingly similar levels of alcoholic steatosis, although there were underlying differences in the pattern of hepatic lipid accumulation and expression of genes involved in hepatic lipid metabolism. Follow‐up studies in Dgat1−/− mice revealed that these animals are protected from alcoholic steatosis when consumed as part of a high‐fat diet, but not a low‐fat diet. Conclusions: Dietary macronutrient composition influences the relative contribution of DGAT1 and DGAT2 to alcoholic steatosis, such that in the context of alcohol and a high‐fat diet, DGAT1 predominates. The pathogenesis of alcoholic fatty liver disease is an active area of research. As the only enzymes capable of catalyzing the final step in triglyceride synthesis, Diacylglycerol O‐acyltransferase (DGAT) 1 and 2 are important contributors to alcoholic steatosis. Our data indicate that the relative contribution of DGAT1 and DGAT2 to alcohol‐induced hepatic triglyceride accumulation depends on dietary macronutrient composition. Thus, in the context of chronic alcohol consumption and a high‐fat diet, DGAT1 is the predominant contributor to alcoholic steatosis. [ABSTRACT FROM AUTHOR]

Sinonasal carcinosarcomas represent rare neoplasms, with aggressive character and unfavourable prognosis. We present a case of extensive sinonasal carcinosarcoma extending into the anterior cranial fossa and into the orbit and also a review of the current international literature regarding this rare yet aggressive neoplasm. There is currently a lack of specific guidelines on the optimal management of sinonasal carcinosarcoma and the treatment represents a challenge for the clinician. The key message that we would like to disseminate to our colleagues is the importance of suspicion and early detection, as well as the necessity to adopt a holistic approach when counselling patients. [ABSTRACT FROM AUTHOR]

Retinoic acid signaling is required for maintaining a range of cellular processes, including cell differentiation, proliferation, and apoptosis. We investigated the actions of all-trans-retinoic acid (atRA) signaling in pancreatic β-cells of adult mice. atRA signaling was ablated in β-cells by overexpressing a dominant-negative retinoic acid receptor (RAR)-α mutant (RARdn) using an inducible Cre-Lox system under the control of the pancreas duodenal homeobox gene promoter. Our studies establish that hypomorphism for RAR in β-cells leads to an age-dependent decrease in plasma insulin in the fed state and in response to a glucose challenge. Glucose-stimulated insulin secretion was also impaired in islets isolated from mice expressing RARdn. Among genes that are atRA responsive, Glut2 and Gck mRNA levels were decreased in isolated islets from RARdn-expressing mice. Histologic analyses of RARdn-expressing pancreata revealed a decrease in β-cell mass and insulin per β-cell 1 mo after induction of the RARdn. Our results indicate that atRA signaling mediated by RARs is required in the adult pancreas for maintaining both β-cell function and mass, and provide insights into molecular mechanisms underlying these actions. [ABSTRACT FROM AUTHOR]

Retinoids (vitamin A and its analogs) are highly potent regulators of cell differentiation, cell proliferation, and apoptosis. Because of these activities, retinoids have been most extensively studied in the contexts of embryonic development and of proliferative diseases, especially cancer and skin disease. Recently, there has been considerable new research interest focused on gaining understanding of the roles that retinoids and/or retinoid-related proteins may have in the development of metabolic diseases, primarily obesity, diabetes, and dyslipidemia. This review will summarize recent advances that have been made in these areas, focusing on the role of retinoids in modulating adipogenesis, the roles of retinoids and retinoid-related proteins as signaling molecules linking obesity with the development of type II diabetes, the roles of retinoids in pancreatic β-cell biology/insulin secretion, and the actions of retinoids in hepatic steatosis. © 2012 BioFactors, 2013 [ABSTRACT FROM AUTHOR]