UCLA geneticists
have created a technique to hunt for hormones that influence how organs
and tissues communicate with each other. The method enabled them to find
naturally occurring molecules that play major roles in Type 2 diabetes,
obesity and cardiovascular disease.
In particular, they discovered:
- Two hormones called “notum” and “lipocalin-5” that speed up the body’s ability to burn fat.
- Lipocalin-5 protected mice from developing diabetes — or cured the disease after they developed it.
- Lipocalin-5 also enhanced muscle tissue’s ability to metabolize and
absorb dietary nutrients, reducing the risk of obesity and diabetes.
The findings could deepen scientists’ understanding of the mechanisms
behind obesity and common risk factors for heart disease and diabetes.
BACKGROUND
Diseases such as obesity and diabetes disrupt how individual tissues
and organs communicate with one another. The technique developed by the
UCLA researchers reverses this disruption by pursuing alternate routes
of tissue-to-tissue communication.
METHOD
The researchers developed a data-driven approach to unravel the wide
array of functions for hormones that circulate in the bloodstream. They
initially identified and studied the hormonal networks in mice. Next
they tested whether the functions they assigned to the hormones remained
consistent in humans. The team discovered a strong overlap between
these hormones’ functions in mice and humans. By studying how hormonal
functions change in people with diabetes and cardiovascular disease, the
scientists were able to identify new ways that tissues signal each
other and restore normal communication.
IMPACT
Future studies will address how the newly identified hormones in
humans communicate between unrelated types of tissue. The investigators
will also apply the new method to evaluate tissue-to-tissue
communication across different ethnicities and diseases. The hope is to
use these hormones as the basis for drug development — specifically to
halt development of obesity and Type 2 diabetes.
AUTHORS
Authors include
Jake Lusis, a professor of human genetics at the
David Geffen School of Medicine at UCLA, and Marcus Seldin, a postdoctoral fellow in Lusis’ lab. They are available for interviews.
JOURNAL
Cell Metabolism
published the findings on May 1.
FUNDING
The research was supported by grants from the National Heart, Lung and Blood Institute and the Leducq Foundation.
