The work with mice models revealed how the functioning of a key receptor affects the body's ability to burn fat.
How does one hormone system affect both blood pressure and obesity? And how can it behave one way in the brain and differently in other parts of the body?
In a study for Cell Reports, researchers used mouse models to understand the role of the renin-angiotensin system, or RAS. This hormone system is often targeted in treating high blood pressure, but using drugs that block RAS.
In the brain, RAS acts to increase resting metabolism, cause more energy expenditure and weight loss. But when RAS activity is elevated in the body—known as peripheral RAS—it decreases resting metabolism and causes weight gain.
The study involved genetically modified mice with highly elevated brain RAS, which had higher resting metabolic rates—and resulting weight loss—than a control group of mice. Both sets of mice were given similar amounts of food and physical activity.
How does this occur? Mice with the elevated brain RAS had increased heat production in the fat around their hips. This subcutaneous fat is considered less of a health risk than visceral fat, which accumulates around the abdomen and key organs, such as the liver and pancreas.
But, when the researchers activated a key receptor in the subcutaneous fat cells, known as AT2, the mice began to gain weight even though their food intake did not change. This suggests that the AT2 behaved the same way peripheral RAS does in lowering the metabolic rate. Futhermore, the team identified found that their actions to activate the receptor reduced a key protein that generates heat in the fat cells.
Justin Grobe, PhD, a University of Iowa researcher involved in the study, said the work revealed how activating the AT2 receptors disrupts the process that fat cells use to create heat, or burn calories. Too much angiotension leads to obesity, he said, because the receptors are “telling the body to slow down its metabolism as the body gets bigger.”
This paradox, that the metabolism slows as obesity gets worse, explains why it is so hard for people to lose weight once they gain it, and why keeping pound off after weight loss is so difficult.
Littlejohn NK, Keen HL, Weidemann BJ, et al. Suppression of resting metabolism by the angiotensin AT2 receptor [published online July 28, 2016]. Cell Reports. 2016; DOI: http://dx.doi.org/10.1016/j.celrep.2016.07.003