First discovered in 1979, natriuretic peptides (NPs) play a variety of roles in the body, some not yet understood. But atrial and B-type NPs, hormones produced by the heart, have been discovered as vital for regulating metabolism, and scientists from the Sanford Burnham Prebys Medical Discovery Institute (SBP) see potential for NPs as therapeutic targets in treating obesity and diabetes.
Scientists already knew that NPs could balance levels of salt and water in the body to play a part in blood pressure regulation. But, depending on the specific tissue type that NPs reside and are active in, these hormones could be extremely important for preventing obesity and insulin resistance.
"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,” explained senior author Sheila Collins, PhD. "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."
NP activity is largely determined by two natriuretic peptide receptors (NPRs), A and C. NPs use NPRA to “transmit their signals,” but NPRA, a “clearance receptor,” binds NPs and takes them away from the circulation. A 2014 study reported that NPRC levels are greater than NPRA and another receptor, NPRB, in most tissues.
However, depending on which tissue NPRCs are present or absent in, the protective capabilities of NPs change drastically. In the SBP study, researchers illustrated the impact of a lack of NPRCs in skeletal muscle tissue versus in adipose tissue (fat).
Their study included mice with NPRC receptors knocked out in each tissue type. Although all mice were fed a high-fat diet, the lack of NPRC receptors in skeletal muscle tissue, meaning that NPs were free to be active, had no protective effect from obesity and insulin resistance. But in adipose tissue, the absence of NPRCs reflected several desirable effects:
Increased sugar uptake in brown fat, which is particularly capable of burning energy
Improved sensitivity to insulin, which reduces the risk of diabetes development
Less inflammation, which can promote several chronic diseases
"In mice without NRPCs in adipose tissue the liver was completely clean and completely devoid of stored lipids,” Collins said. In normal situations, mice fed this diet would be expected to develop fatty deposits in the liver.
The image shows 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
The findings from the present study highlight NPs as potential therapeutic targets for preventing diseases stemming from dysfunctional metabolism as a result of a high-fat diet. However, applying this type of therapy is tricky, because NPs are also involved with regulating blood pressure.
“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,” Collins clarified.
Whether it’s suppressing NPRC receptors, promoting NPRA receptors, or a mixture of both, there are several possibilities for Collins and her team to pursue in the future.
The present study was published in the journal Science Signaling.