The impact of mitochondrial oxidative stress on bile acid-like molecules in C. elegans provides a new perspective on human metabolic diseases

Abstract

C. elegans is a model used to study cholesterol metabolism and the functions of its metabolites. Several studies have reported that, in worms, cholesterol is not a structural component of the membrane as it is in vertebrates. However, as in other animals, it is used for the synthesis of steroid hormones that regulate physiological processes such as dauer formation, molting and defecation. After cholesterol is taken up by the gut, mechanisms of transport of cholesterol between tissues in C. elegans involve lipoproteins, as in mammals. A recent study shows that both cholesterol uptake and lipoprotein metabolism in C. elegans are regulated by molecules whose activities, biosynthesis, and secretion strongly resemble those of mammalian bile acids, which are metabolites of cholesterol that act on metabolism in a variety of ways. Importantly, it was found that oxidative stress upsets the regulation of the synthesis of these molecules. Given the known function of mammalian bile acids as metabolic regulators of lipid and glucose homeostasis, future investigations of the biology of C. elegans bile acid-like molecules could provide information on the etiology of human metabolic disorders that are characterized by elevated oxidative stress.