Insights into fat signaling could boost the fight against obesity and diabetes

Natriuretic peptides, or NPs, send signals in adipose tissue that can turn harmful white fat into energy-burning brown fat. But NP signaling may have an even broader role in protecting against metabolic disease.

NPs are made in the heart and are known to modulate water and salt in the control of blood pressure. Now, scientists at Florida’s Sanford Burnham Prebys Medical Discovery Institute have discovered that when they dial up NP signaling in adipose tissue of mice, they can prevent obesity and increase sugar uptake in brown fat. The research was published in the journal Science Signaling.

The researchers made the discovery by studying mice that lack certain receptors that normally remove NPs from circulation. When those receptors were removed from adipose tissue and the animals were fed a high-fat diet, they not only showed improved insulin sensitivity, they also suffered less inflammation and burned more energy.

"Usually when you feed mice high-fat diets they get fatty liver," said senior author Sheila Collins, Ph.D., professor in the Integrative Metabolism Program at Sanford Burnham, in a press release. "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."

Previous research has shown that naturally thin people have higher levels of NPs in their blood. But when NP clearance is elevated in fat tissue, the amount of the peptide in the blood falls, making it difficult for healthy signaling to occur.

There is a major effort underway in the scientific community to promote the conversion of unhealthy white fat to beneficial brown fat. Last year, a team at the University of Pennsylvania discovered that the protein FLCN works with the mTOR protein complex to suppress the browning of white fat, and when they deleted FLCN in mice, their white cells started to turn brown.

Collins and her colleagues believe their findings validate approaches that target adipose tissue. Possibilities for translating their findings into anti-obesity drugs might include making peptides that do a better job of binding to the signaling form of the NP receptor than they do to the clearance version, she says. Alternately, they could develop agents that inhibit the clearance receptor. The researchers are planning further studies to better understand the relationships between NPs, white fat and brown fat.