Chronic overnutrition is linked to ER stress in a variety of tissues,16, 17, 18 and ER stress is implicated in pathophysiological mechanisms involving metabolic hormones.19, 20 Here, uroguanylin loss by DIO (P<0.01; Figure 2a) was associated with increased expression of the canonical ER stress marker, BiP (GRP78, HSPA5),21 in jejunal epithelia (P<0.001; Figure 2b). The gene discussed is GUCA2B; the disease is overnutrition.