Increasing a protein concentrated in brown fat appears to lower blood sugar, boost insulin sensitivity, and protect against fatty liver disease by converting white fat to a healthier state, suggests a new study led by scientists at UT Southwestern. The results, published online in Nature Communications, could eventually lead to new solutions for patients with diabetes and related diseases.
By using this natural system, we can potentially help make fat deposits metabolically healthier and potentially prevent or treat obesity-associated diabetes. “
Perry E. Bickel, MD, study director, associate professor of internal medicine at UTSW
Ten million Americans have type 2 diabetes, a disease characterized by high blood sugar and resistance to insulin, the hormone that enables cells to use blood sugar for energy. This disease has been linked to obesity, and excess white adipose tissue (WAT) – fat tissue that contains most of the energy stored in the body – has been linked to increased blood sugar and insulin resistance in susceptible people. Humans and other mammals also have a second type of fat known as brown adipose tissue (BAT) that is capable of burning fat to increase body heat in cold temperatures. BAT has been studied as a potential target for weight loss, says Bickel, but it may also play a role in improving blood sugar regardless of weight loss.
In the study, Bickel and his colleagues, including co-director Violeta I. Gallardo-Montejano, MD, an instructor at UTSW, found that brown fat could play an important protective role against diabetes. The researchers made this discovery while studying perilipin 5 (PLIN5), a protein that coats lipid droplets in cells, particularly BAT.
When the team genetically engineered mice that produced additional PLIN5 in BAT, the animals retained significantly lower blood sugar levels and higher insulin sensitivity compared to mice with normal PLIN5 levels during the glucose tolerance tests. They also had fewer levels of fatty liver, a condition linked to type 2 diabetes.
While searching for the mechanism behind these positive changes, the scientists found that the mitochondria of the BAT in the genetically engineered mice had adapted to burn even more fat, similar to animals kept in cold temperatures. However, the adjustment was insufficient to explain the hypoglycemic effects. Upon closer inspection, the researchers found that the white adipocytes of animals that had extra PLIN5 in their brown adipocytes were smaller and some markers of inflammation were reduced – changes associated with improved sensitivity to insulin and sugar metabolism.
Bickel notes that when the PLIN5 levels in brown adipocytes rise, BAT appears to communicate with WAT in an unknown manner, possibly sending a molecular factor through the bloodstream.
“The next question we want to ask ourselves,” says Bickel, “is what kind of factor that is and whether we can use it therapeutically.”
UT Southwestern Medical Center
Gallardo-Montejano, VI, et al. (2021) Perilipin 5 combines mitochondrial decoupled breathing in brown fat with healthy conversion of white fat and systemic glucose tolerance. Nature communication. doi.org/10.1038/s41467-021-23601-2.