Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet

Abstract

Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism.

GLP-1/Glucagon Coagonism Restores Leptin Responsiveness in Obese Mice Chronically Maintained on an Obesogenic Diet

“…Plasma levels of insulin (Crystal Chem, Inc., Downers Grove, IL), cholesterol (Wako Chemicals, Neuss, Germany), leptin (ALPCO Diagnostics, Salem, NH), and adiponectin (Millipore, Schwalbach, Germany) were measured using commercially available kits according to the manufacturers' instructions. Levels of liver triglycerides were assessed as previously described (21).…”

Markers of endothelial cell dysfunction are increased in human omental adipose tissue from women with pre-existing maternal obesity and gestational diabetes

“…It is thus possible that increased secretion of angiogenic molecules from obese and GDM adipose tissue may be responsible for the increase in placental and adipose tissue inflammation observed in these conditions [27,[74][75][76][77][78]. They may also act as physiological mediators of lipid and glucose metabolism; heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels [79]. Therefore, it is feasible that increased adipose tissue endoglin secretion may lead to higher circulating lipid levels leading to excess substrate supply that drives maternal-fetal energy transfer and increased neonatal adiposity.…”