Heart hormones protect against obesity and insulin resistance

August 25, 2017, Sanford-Burnham Prebys Medical Discovery Institute
Hematoxylin and eosin staining of gonadal white adipose tissue from a control mouse on a high-fat diet. Credit: Wei Wu/Sanford Burnham Prebys Medical Discovery Institute, Orlando, USA, and Fudan University, Shanghai, China

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) in Lake Nona, Florida have shown that enhanced natriuretic peptide (NP) signaling in adipose tissue protects against obesity and insulin resistance. The findings suggest that boosting levels of NPs in adipose tissue may be an important avenue to explore for combating metabolic disease. The study was published in Science Signaling.

"For years we have known that NPs control blood pressure and can promote the conversion of energy-storing 'bad' into energy-burning 'good' , says Sheila Collins, Ph.D., professor in the Integrative Metabolism Program at SBP Lake Nona and senior author on the paper. "What we discovered in this study is the important role for NPs in managing metabolism and resisting the deleterious effects of a high-fat diet."

Made in the heart, atrial and B-type natriuretic peptides (NPs) are hormones that were originally discovered to modulate salt and water to control blood pressure. These peptides transmit their signals through natriuretic peptide receptor A (NPRA). Meanwhile, natriuretic peptide receptor C (NPRC) removes NPs from circulation.

"We wanted to explore the difference between elevated levels of NPs in compared to . Understanding the distinctions can help us devise strategies and treatments to potentially improve metabolic health—including obesity and ," says Collins.

To study this interplay, the researchers studied mice with NPRC receptors selectively knocked out in either adipose or skeletal muscle . While deleting NPRC in muscle provided no protection from a high-fat diet, eliminating the receptor in adipose tissue improved insulin sensitivity, prevented obesity and increased sugar uptake in metabolism-boosting brown fat. In addition, the adipose knockout mice showed higher energy expenditure and less inflammation.

"Usually when you feed mice high-fat diets they get fatty liver," says Collins. "In mice without NRPCs in adipose tissue the liver was completely clean and completely devoid of stored lipids, which I'm sure contributes to their improved overall metabolic performance."

These findings dovetail with clinical research that has shown naturally lean people tend to have higher NP concentrations in their blood. By contrast, NP clearance tends to rise in fat tissue, removing these peptides from the blood and making it more difficult for effective NP signaling to happen.

Around a third of adults in the U.S. are obese, increasing their risk for type 2 diabetes, metabolic syndrome, fatty liver disease and other conditions. With these results, scientists can begin exploring NPs as therapeutic targets. This will require intense investigation, as any effective treatment must avoid adverse effects on . While this study increased the NP signal by knocking out NPRCs, another approach might be to focus on NPRAs.

"I think this further reinforces that it is really the adipose tissue that's an important site to take advantage of this signaling mechanism," says Collins. "We could make versions of these that bind to the signaling form (NPRA) of the receptor better than the clearance form, or we could make agents that are only are recognized by the clearance receptor, thus providing better access of the NPs to NPRA.

"However, before any therapy can move forward, more work must be done to better understand these protective mechanisms and unwind the complex interrelationships between NPs, white fat, brown fat and possibly other players," adds Collins.

Explore further: Researchers reveal new links between heart hormones, obesity, and diabetes

More information: Wei Wu et al, Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity and insulin resistance, Science Signaling (2017). DOI: 10.1126/scisignal.aam6870

Related Stories

Researchers reveal new links between heart hormones, obesity, and diabetes

February 17, 2016
A new research study has revealed an important relationship between proteins secreted by the heart and obesity, glucose intolerance, and insulin resistance. The findings, published today in Obesity, offer a new approach to ...

Heart hormone helps shape fat metabolism

February 6, 2012
It's well known that exercising reduces body weight because it draws on fat stores that muscle can burn as fuel. But a new study at Sanford-Burnham Medical Research Institute (Sanford-Burnham) suggests that the heart also ...

More blood vessels in adipose tissue may alleviate type 2 diabetes

April 12, 2016
Researchers at Wihuri Research Institute and University of Helsinki, Finland, in collaboration with scientists from Vanderbilt and Groningen Universities used recombinant gene transfer technologies to discover a fine-tuning ...

Scientists propose novel therapy to lessen risk of obesity-linked disease

July 24, 2017
With obesity related illnesses a global pandemic, researchers propose in the Journal of Clinical Investigation using a blood thinner to target molecular drivers of chronic metabolic inflammation in people eating high-fat ...

Omega-3 fatty acids stimulate brown adipose tissue metabolism

November 22, 2016
Omega-3 fatty acids are able to stimulate the activation of brown and beige adipose tissues, a discovery that would promote the development of new therapies for obesity and other metabolism diseases, according to a research ...

Study examines role of ghrelin receptor in fat tissue inflammation and insulin resistance  

August 23, 2016
Scientists have proposed that inflammation is the harbinger of aging and central to the aging process, a phenomenon described as 'inflamm-aging,' said Dr. Yuxiang Sun.

Recommended for you

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Researchers give new insight to muscular dystrophy patients

December 13, 2018
New research by University of Minnesota scientists has revealed the three-dimensional structure of the DUX4 protein, which is responsible for the disease, facioscapulohumeral muscular dystrophy (FSHD). Unlike the majority ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.