Estrogen receptor knockout ER−/−(ERKO, BERKO or viral-mediated ER suppression mouse):↓ glucose tolerance; whole body and hepatic insulin sensitivity; insulin-stimulated glucose uptake by skeletal muscle; blood adiponectin, testosterone; sexual behavior↑ body weight; abnormalities in vascular smooth muscle cells (ion channel function); systolic and diastolic blood pressure; arterial pressure; heart failure; hepatic lipid biosynthesis; adipose tissue mass; blood glucose, insulin, leptin. Here, ESR1 is linked to heart failure.