Nav: Home

Blood pressure hormone promotes obesity

July 28, 2016

New research by University of Iowa scientists helps explain how a hormone system often targeted to treat cardiovascular disease can also lower metabolism and promote obesity.

The renin-angiotensin system (RAS) controls blood pressure and is important for cardiovascular health. Many of the drugs used to treat hypertension (high blood pressure) and heart failure block or inhibit the RAS.

Increasing evidence suggests the RAS also plays a role in controlling energy balance and metabolic rate and therefore may be important in obesity. But, depending on where in the body this hormone system is operating, it can have opposing effects on weight gain.

When the RAS is elevated in the brain, it increases energy expenditure by increasing resting metabolism, resulting in weight loss. However, increased activity of the RAS circulating in the body (the peripheral RAS) -- which occurs during obesity in humans and experimental animals -- has the opposite effect, decreasing resting metabolism and increasing weight gain.

"At a very simplistic 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," explains Justin Grobe, PhD, UI assistant professor of pharmacology and senior author of a new study that shows how the peripheral RAS suppresses resting metabolism.

The new findings, published Aug. 9 in the journal Cell Reports, shows that in mice, circulating angiotensin reduces resting metabolic rate by activating its less common receptor (angiotensin II type 2 receptor or AT2) specifically on subcutaneous fat cells.

A more precise understanding of how the RAS acts in tissue-specific and receptor-specific ways to influence energy balance may ultimately be useful for developing new ways to treat obesity and the health problems associated with it.

Grobe and his colleagues, including lead study author Nicole Littlejohn, PhD, studied genetically modified mice that have a hyper-activated brain RAS. These mice have increased resting metabolic rate and weight loss compared to control mice despite having similar levels of food intake and physical activity.

The researchers discovered that the increased resting metabolic rate in the mice is due to increased heat production (thermogenesis) in the pads of subcutaneous fat at the animals' hips. This type of fat is often considered "healthy." In contrast, the abdominal fat surrounding the internal organs, which is thought to be "unhealthy," did not show increased thermogenesis.

When the researchers activated AT2 receptors on the subcutaneous fat cells, the mice gained weight without changing feeding behavior, suggesting that activating AT2 receptors decreases resting metabolic rate. Activating AT2 mimics what would happen when the peripheral RAS is elevated.

Specifically, the team found that activating AT2 receptors reduces the amount of UCP1 protein made in the subcutaneous fat cells. This protein is important for non-shivering heat production. Reduced amounts of UCP1 interferes with the capacity of the fat cells to make heat.

"If the fat cell is the thermogenic tissue (generating heat by burning calories), you can either have a bigger engine or you can push the gas pedal harder to create a larger effect," Grobe says. "Our study shows that angiotensin is modulating the size of the engine (amount of UCP1), not how hard the gas pedal is being pushed."

The team also looked for other signaling pathways affected by AT2 activation. Using gene expression profiling, they homed in on a set of genes involved in the epidermal growth factor (EGF) signaling pathway. EGF signaling is known to contribute to the differentiation of fat cells. The new findings suggest that angiotensin activating AT2 receptors in subcutaneous fat cells interferes with this process, although the precise molecular mechanism is not yet known.

"In multiple ways, activation of the AT2 receptor [by increasing the peripheral RAS] is interfering with the capacity of the cell to make heat," Grobe says. "It is very consistent with the clinical observation that peripheral angiotensin goes up during obesity. This is probably at least one of the mechanisms by which that excess angiotensin is perpetuating obesity. Because it is telling the body to slow down its metabolism as the body gets bigger."
-end-
The research involved collaboration between several UI labs in the Department of Pharmacology (led by Grobe; Curt Sigmund, the department chair; Kamal Rhamouni; and Matthew Potthoff) and the Department of Microbiology (led by Aloysius Klingelhutz). Study team members also belong to the following UI research centers and initiatives: the Fraternal Order of Eagles Diabetes Research Center, the Francois M. Abboud Cardiovascular Research Center, the Center for Hypertension Research, and the Obesity Research and Education Initiative.

The research was funded in part by grants from the American Diabetes Association, the American Heart Association, and the National Institutes of Health, including the Program Project Grant "Genetic and Signaling Mechanisms in the Central Regulation of Blood Pressure," led by Sigmund that has been continuously funded since 2006.

University of Iowa Health Care

Related Obesity Articles:

Should obesity be recognized as a disease?
With obesity now affecting almost a third (29%) of the population in England, and expected to rise to 35% by 2030, should we now recognize it as a disease?
Is obesity associated with risk of pediatric MS?
A single-center study of 453 children in Germany with multiple sclerosis (MS) investigated the association of obesity with pediatric MS risk and with the response of first-line therapy in children with MS.
Women with obesity prior to conception are more likely to have children with obesity
A systematic review and meta-analysis identified significantly increased odds of child obesity when mothers have obesity before conception, according to a study published June 11, 2019 in the open-access journal PLOS Medicine by Nicola Heslehurst of Newcastle University in the UK, and colleagues.
Obesity medicine association announces major updates to its adult obesity algorithm
The Obesity Medicine Association (OMA) announced the immediate availability of the 2019 OMA Adult Obesity Algorithm, with new information for clinicians including the relationship between Obesity and Cardiovascular Disease, Diabetes Mellitus, Dyslipidemia, and Cancer; information on investigational Anti-Obesity Pharmacotherapy; treatments for Lipodystrophy; and Pharmacokinetics and Obesity.
Systematic review shows risk of a child developing overweight or obesity is more than trebled by maternal obesity prior to pregnancy
New research presented at this year's European Congress on Obesity (ECO) in Glasgow, Scotland (April 28- May 1) reveals that the risk of a child becoming overweight or obese is more than trebled by maternal obesity prior to getting pregnant.
More Obesity News and Obesity Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...