ESR1 and Insulin resistance: Mice lacking ER have increased adipose tissue, higher fasting blood glucose and insulin30 and hepatic insulin resistance with altered hepatic lipid handling.26, 31 Furthermore, deletion of ERα in mice blocks the antiobesity effects of estrogen replacement.29 Male mice lacking ER specifically in the liver show reduced insulin sensitivity.26 Conversely, hepatic ERα overexpression is associated with markedly reduced hepatic triglyceride content and improved insulin sensitivity.32