ESPE Abstracts

Background: Brown adipose tissue (BAT) was thought to exist only from birth to infancy and not in adults. However, it has recently been found to be present in adults as well, drawing significant attention as a target for anti-obesity drugs due to its characteristic of energy expenditure independent of exercise. ACE2 converts Angiotensin II (AngII) to Angiotensin 1-7 and antagonizes the ACE/AngII system through Mas receptor. We have previously reported that administration of ACE2/Ang1-7 activates BAT and exhibits anti-obesity effects in young obese model mice. However, the age-related differences in the response to this effect are not yet understood.

Objective: To investigate the age-related differences in the anti-obesity effects of Ang1-7

Methods: We created groups of mice by feeding 4-week-old C57/BL6 mice high-fat diet (HFD) for one month (young obese group) followed by one month of Ang1-7 administration, and another group by feeding HFD for three months (aged obese group) followed by one month of Ang1-7 administration. After Ang1-7 administration, we conducted intraperitoneal glucose tolerance tests (IPGTT), intraperitoneal insulin tolerance tests (IPITT), measurement of oxygen consumption, rectal temperature measurement under cold stimulation, measurement of various organ weights, tissue evaluation, and lipidome analysis.

Results: In the young obese group, Ang1-7 administration decreased body weight concomitant with increased oxygen consumption and increased rectal temperature under cold stimulation. However, in the aged obese group, there was no difference compared to the control group, and no decrease in body weight was observed even with Ang1-7 administration. BAT weight increased in the young obese group but decreased in the aged obese group. The number of large adipocytes decreased in the young obese group compared to the aged obese group. Lipidome analysis showed differences in lipid composition, such as an increase in linolenate and capric acid in the young obese group, while they decreased in the aged obese group.

Conclusion: Activation of BAT by Ang1-7 administration shows age-related differences, and it is considered more effective to initiate anti-obesity treatment targeting BAT in childhood. Additionally, these data suggest differences in fatty acid composition may be involved in BAT differentiation, leading to the development of BAT activation-based therapies in the future.