In This Issue of Diabetes

摘要

Mueller et al. studied the role of the glucocorticoid receptors in adipose tissue, revealing a central role for the receptor in controlling energy metabolism and partitioning of nutrients during times of fasting and feeding. Involving a mouse model with the gene for the receptor knocked out only in adipocytes and controls, the study used metabolomics and a series of biological and molecular techniques to pick apart how much of an impact the receptor likely has on global metabolism. The authors report considerable changes in circulating metabolites relating to lipid metabolism or amino acid metabolism and reduced lipolytic and gluconeogenic capacity in the mice lacking the receptor genes. Furthermore, exposing these mice to cold reportedly resulted in reduced thermogenesis capacity, again supporting impaired lipolytic function. Subsequent molecular analyses suggested that the receptor knockout was likely responsible for the impaired signal transduction from β-adrenergic receptors to adenylate cyclase and the normal activation of the lipolytic cascade in adipose tissue. They report further that diet-induced or aging-associated obesity was reduced and the development of liver steatosis and deterioration of glucose metabolism was attenuated in mice with no glucocorticoid receptors. Taken together, the results suggest that the glucocorticoid receptor in adipocytes likely exerts central but diverging roles in metabolic homeostasis that are dependent on energetic state and, in certain circumstances, might promote adiposity and associated disorders. Commenting more widely on the study, authors Richard Moriggl and Jan P. Tuckermann told Diabetes. "Apart from underlining that systemic energy metabolism, at least in part, is controlled centrally via the adipocyte glucocorticoid receptor, our studies suggest that inhibition of the glucocorticoid pathway in adipose tissue may lead to conditions which prevent the gain of fat mass in a metabolically harmful manner. Age- and malnutrition-associated diseases like obesity can promote serious diseases such as liver cancer or cardiovascular disease. If we can better define the role of glucocorticoids in adipose tissue under these conditions, we might be able to identify new strategies to counteract obesity-related complications. Future studies to reveal underlying mechanisms and potential therapeutic implication are thus warranted."