Ahdc1 is a potent regulator of obesity and energy metabolism

Abstract

AT-hook DNA-binding domain protein 1 (AHDC1) is a causal gene of intellectual disability/developmental delay in humans. The biological role of AHDC1 is unclear. Recently some clues from AHDC1 mutation carriers hinted that AHDC1 may participate in body-weight regulation. In this first metabolic phenotype study of Ahdc1 deficiency, we generated a Ahdc1-deficienct mouse line and found that Ahdc1 deficiency in both male and female mice led to adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient, with progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. Our findings show that Ahdc1 is a novel key regulator of obesity and energy metabolism, which provides new insight into the physiologic mechanisms of obesity.