Link between Renin-angiotensin System and Weight Gain

Discovering new approaches to battle obesity is a key target for investigators, given that the problem is an increasing public health concern. Now, a new research presented in the journal Cell Reports, sheds light on how the renin-angiotensin system, the hormone system that manages blood pressure – may also promote unwanted weight gain. The finding provides a possible target for obesity therapy.

While the role of the renin-angiotensin system (RAS) in blood pressure management is well recognized, earlier research have suggested the RAS is also engaged in energy balance and metabolism, indicating the hormone system impacts weight.

According to a Senior study author Justin Grobe and colleagues, whether RAS promotes weight gain or weight loss relies upon where in the body it is active. For instance, if the RAS is extremely active in the brain, it raises energy expenditure by enhancing resting metabolism, which results in weight loss.

However, if peripheral RAS activity is enhanced – that is, if there are great levels of the RAS hormone angiotensin circulating in the remaining body – it decreases resting metabolism, resulting in weight gain. Heightened peripheral RAS is usually identified in obese persons.

“At a very simple level, you can think of the brain RAS as the gas pedal on metabolism and the peripheral (circulating) RAS as the brake, with angiotensin as the driver,” describes Grobe.

For their research, Grobe and colleagues determined to examine the mechanisms by which the peripheral RAS dampens resting metabolism, with the purpose of bringing us nearer to an approach that could stop this process.

Peripheral RAS promotes obesity via decreased thermogenesis

The research team examined mice that had been genetically modified to have extremely heightened RAS activity in the brain.

In comparison with control mice, the genetically modified mice had higher resting metabolic rate and weight loss, although they had the same diet and physical exercise levels.

On examining the fat tissue of the two groups of mice, the investigators identified that the subcutaneous fat on the hips of the genetically modified mice demonstrated enhanced heat production – or thermogenesis – while visceral fat surrounding the inner organs did not.

Subcutaneous fat relates to fat that is directly under the skin, and it is regarded by some health experts as a “healthy” fat. Visceral fat, however, which is placed deep in the abdominal area, is regarded an “unhealthy” fat, increasing the risk of obesity-related diseases, like as diabetes and heart disease.

Next, the study team triggered a receptor known as angiotensin II type 2 (AT2) in the subcutaneous fat cells of the mice. AT2 is generally activated when the peripheral RAS is enhanced.

Following the AT2 receptor was triggered, the investigators identified the mice obtained weight, regardless of experiencing no modifications in diet or food consumption.

In detail, they identified that AT2 activation decreases the production of a protein known as UCP1 in subcutaneous fat cells, which is essential for non-shivering thermogenesis. Decreased UCP1 levels impair fat cells’ capability to generate heat, the team notes.

“If the fat cell is the thermogenic tissue (producing heat by burning calories), you can either have a larger engine or you can push the gas pedal harder to generate a larger effect,” describes Grobe. “Our research demonstrates that angiotensin is modulating the size of the engine (amount of UCP1), not how tough the gas pedal is being pushed.”

Over-all, the investigators say their results recommend that enhanced peripheral RAS activity – via enhanced angiotensin levels – promotes obesity via AT2 activation and impaired thermogenesis.