Increasing a Protein in Adipose Tissue Can Improve Metabolism

Scientists at UT Southwestern Medical Center (UTSW) found that increasing a protein in brown adipose tissue can lower blood sugar, promote insulin sensitivity, and prevent fatty liver disease by reshaping white fat into a healthier state. Their mouse research may one day eventually lead to new treatments and options for type 2 diabetes and other metabolic-related diseases.

Brown fat, also known as brown adipose tissue (BAT), is a type of body fat that is activated when we feel cold. Brown fat has always been an interesting topic because researchers have discovered that it can use regular body fat as fuel, and exercise may stimulate hormones to activate it. Now, a new study by scientists at UT Southwest Medical Center (UTSW) shows that raising a protein found in BAT can lower blood glucose, promote insulin sensitivity, and prevent fatty liver disease by remodeling white fat to a healthier state.

Their research was published in Nature Communications. This discovery may eventually provide new treatment options for type 2 diabetes (T2D) and metabolic-related diseases.

"Mice or humans exposed to the cold can promote significant changes in BAT in histology, lipid content, gene expression, and mitochondrial quality and function. Here, we report the lipid droplet coat protein Perilipin 5 (PLIN5) in BAT. It increased significantly when mice were exposed to cold."

"By taking advantage of this natural system, we may be able to help make fat storage more metabolically healthier, and potentially prevent or treat obesity-related diabetes," explained research leader Perry E. Bickel, MD, associate professor of internal medicine at UTSW.

Researchers genetically engineered mice to produce extra PLIN5 in BAT. In the glucose tolerance test, compared with mice with normal PLIN5 levels, these animals have significantly lower blood glucose concentrations and higher insulin sensitivity.

They also found that the BAT mitochondria in the transgenic mice had adapted to burn more fat, similar to animals placed in a cold environment. After careful observation, the researchers found that animals with additional PLIN5 in the brown fat cells had smaller white fat cells and reduced some markers of inflammation. These changes were related to the improvement of insulin sensitivity and glucose metabolism.

"The next problem we want to solve is," Bickel said, "what is the factor, and can we use it to treat it."

"Human brown or beige adipose tissue is a promising target for the development of drugs for the treatment of type 2 diabetes, and the idea is supported by our results that increasing PLIN5 in BAT of mice promotes glucose tolerance, healthy remodeling of iWAT, and the protective effect of diet (HFD) on hepatic steatosis," the researchers wrote. "We have shown that more PLIN5 in brown adipocytes enhances the oxidation function of mitochondria and promotes the uptake and oxidation of BAT fatty acids. Our research shows that PLIN5 may mimic the effect of low temperature on bats, thus improving systemic glucose tolerance and preventing Diet-induced liver steatosis."