Obesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential.

Although there have been a few studies investigating the location of teleost fish aquaporins. To date little is still known concerning this topic. In the eel, eleven aquaporin genes have been cloned and sequenced from osmoregulatory tissues such as gill, gut and kidney and custom antibodies raised against specific aquaporin peptide antigens. Results show that eel aquaporin 1 (aquaporin 1) is expressed in the apical membranes of a subset of renal tubules and in endothelial cells lining blood vessels as shown previously. A duplicate copy of aquaporin1, AQP1dup (AQP1b using zebrafish nomenclature) was also expressed in a subset of renal tubules but was located in vesicles in the apical pole of the tubule cells rather than in the apical membrane. Aquaporin 8 (AQP8ab in zebrafish) was also expressed in a subset of renal tubules but was located in the basal pole of cells and also stained red blood cells, whereas AQP8b (AQP8aa in zebrafish) expression was located in and adjacent to, cells expressing chromogenic pigment granules. Aquaporin 4b, a novel eel aquaporin was expressed in lines or rings of cells, in unknown structures not associated with either renal tubules or blood vessels. For aquaglyceroporins, AQP3 stained only red blood cells whereas AQPe (AQP10b in zebrafish), stained connective tissue with weak staining in the basal pole of some renal tubules.C.P. Cutler is funded by the National Science Foundation NSF IOS 0844818.