Supporting this notion, increasing HMW adiponectin via fat-specific overexpression of DsbA-L, an adipose-abundant protein that promotes adiponectin multimerization, stimulates hepatic AMPK-α phosphorylation at Thr172 that is essential for 5′-AMP-activated protein kinase (AMPK) activation, and ameliorates high-fat diet-induced insulin resistance and hepatosteatosis (Liu et al., 2008, 2012), without affecting AMPK activity in skeletal muscle (Liu et al., 2012). The gene discussed is ADIPOQ; the disease is Insulin resistance.