Heart hormones protect against obesity and insulin resistance

August 25, 2017

Orlando, Fla., Aug. 25, 2017 - 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' white fat into energy-burning 'good' brown fat, 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 adipose tissue compared to skeletal muscle tissue. Understanding the distinctions can help us devise strategies and treatments to potentially improve metabolic health--including obesity and insulin resistance," says Collins.

To study this interplay, the researchers studied mice with NPRC receptors selectively knocked out in either adipose or skeletal muscle tissue. 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 blood pressure. 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 peptides 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.
-end-
This work was supported by the NIH (R01 DK10305).

DOI: 10.1126/scisignal.aam6870

About SBP

Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare children's diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its world-class NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs about 1,100 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

Sanford-Burnham Prebys Medical Discovery Institute

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.