Angiotensinogen-deficient mice exhibit impairment of diet-induced weight gain with alteration in adipose tissue development and increased locomotor activity

White adipose tissue is known to contain the components of the renin-angiot ensin system, which gives rise to angiotensin II from angiotensinogen (AGT) . Recent evidence obtained in vitro and ex vivo is in favor of angiotensin II acting as atrophic factor of adipose tissue development. To determine wh ether AGT plays a role in vivo in this process, comparative studies were pe rformed in AGT-deficient (agt(-/-)) mice and control wild-type mice. The re sults showed that agt(-/-) mice gain less weight than wild-type mice in res ponse to a chow or high fat diet. Adipose tissue mass from weaning to adult hood appeared altered rather specifically, as both the size and the weight of other organs were almost unchanged. Food intake was similar for both gen otypes, suggesting a decreased metabolic efficiency in agt(-/-) mice. Consi stent with this hypothesis, cellularity measurement indicated hypotrophy of adipocytes in agt(-/-) mice with a parallel decrease in the fatty acid syn thase activity. Moreover, AGT-deficient mice exhibited a significantly incr eased locomotor activity, whereas metabolic rate and mRNA levels of uncoupl ing proteins remained similar in both genotypes. Thus, AGT appears to be in volved in the regulation of fat mass through a combination of decreased lip ogenesis and increased locomotor activity that may be centrally mediated.