Angiotensinogen-Deficient Mice Exhibit Impairment of Diet-Induced Weight Gain with Alteration in Adipose Tissue Development and Increased Locomotor Activity

Abstract

White adipose tissue is known to contain the components of the renin-angiotensin 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 a trophic factor of adipose tissue development. To determine whether AGT plays a role in vivo in this process, comparative studies were performed in AGT-deficient (agt(-/-)) mice and control wild-type mice. The results showed that agt(-/-) mice gain less weight than wild-type mice in response to a chow or high fat diet. Adipose tissue mass from weaning to adulthood appeared altered rather specifically, as both the size and the weight of other organs were almost unchanged. Food intake was similar for both genotypes, suggesting a decreased metabolic efficiency in agt(-/-) mice. Consistent with this hypothesis, cellularity measurement indicated hypotrophy of adipocytes in agt(-/-) mice with a parallel decrease in the fatty acid synthase activity. Moreover, AGT-deficient mice exhibited a significantly increased locomotor activity, whereas metabolic rate and mRNA levels of uncoupling proteins remained similar in both genotypes. Thus, AGT appears to be involved in the regulation of fat mass through a combination of decreased lipogenesis and increased locomotor activity that may be centrally mediated.

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats

“…On the other hand, by treating mice with benazepril hydrochloride, another ACEi, Yamamoto et al [23] have observed an improved locomotor activity in the animals. Using a genetic approach to determine whether angiotensinogen acts as a trophic factor of adipose tissue development, Massiera et al [24] analyzed the phenotype of angiotensinogen knockout mice. The results showed that those mice gain less weight than wildtype mice in response to a regular chow or high fat diet, with specific alteration of adipose tissue mass.…”

Control of Energy Balance by the Brain Renin-Angiotensin System

“…Pharmacological blockade or genetic deletion of any component of the RAS in rodent models results in significant changes in body weight, body composition, food intake, digestive efficiency, physical activity, and/or metabolic rate [10][11][12][13][14][15][16][17][18], while transgenic expression of renin in rats results in obesity [19]. It is surprising to find, then, that the beneficial metabolic effects of modulating the RAS are largely unimpressive in human subjects [59-61, 62•, 63, 64].…”

“…Nonetheless, the relationship between circulating RAS activity and obesity is likely bi-directional. The RAS contributes to energy balance, as genetic [10][11][12][13] and pharmacological [14][15][16][17][18] inhibition of the RAS in rodent models generally results in a negative energy balance (lean animals and/or resistance to weight gain), and chronic elevations in plasma renin activity can lead to obesity [19].…”

Cardiometabolic syndrome: Pathophysiology and treatment

“…Among the local effects, angiotensin II is thought to act as a growth factor for fat cells. Systemically, researchers have expressed the AGT gene in adipose tissue of AGT-knockout mice, creating a transgenic-knockout mouse model in which production of AGT is limited to adipose tissue [72]. In these animals, systemic levels of AGT increased to 10% of wild-type levels, demonstrating that AGT produced in fat cells can enter the circulation.…”