The GR-KLF15 axis promotes suppression of hepatic lipogenesis during fasting.

Abstract

Fasting leads to many physiological changes in peripheral tissues, including the liver, where suppression of de novo lipogenesis through inhibition of sterol regulatory element-binding protein 1 (SREBP-1) expression and/or activity is a key adaptation to preserve glucose for maintenance of blood glucose levels. Yoshinori Takeuchi and colleagues provide novel mechanistic insights into the regulation of SREBP-1 expression during fasting and highlight the importance of the hypothalamic-pituitary-adrenal axis and, particularly, glucocorticoid-induced binding of the glucocorticoid receptor to enhancer regions of the KLF15 (Kruppel-like factor 15) gene as a novel mechanism underlying the suppression of SREBP-1 during fasting.