The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

摘要: The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 the regulation of energy balance metabolism. is expressed hypothalamic brain regions that regulate both metabolism HPA axis activity, suggesting may also modulate function. In order test this possibility, plasma corticosterone levels were measured KO wildtype (WT) before (pre-stress) after (post-stress) a mild stressor (intraperitoneal injection). deficiency increased pre- post-stress corticosterone, loss elevated glucocorticoid tone. Consistent idea, thymus suggestive glucocorticoid-induced thymic involution. decreased mRNA expression receptor (GR), mineralocorticoid (MR), vasopressin 1A hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin expression. whether MR GR affected negative feedback, dexamethasone suppression was performed. Dexamethasone WT mice, feedback unaltered by deficiency. summary, these data suggest obesity-associated normally acts diminish circulating glucocorticoids. This might occur via actions on HPA-regulatory circuitry, and/or indirectly ETV5-induced alterations metabolic factors then influence axis.