Brown fat, also known as brown adipose tissue (BAT), is a type of body fat that is activated when we get cold. Brown fat has been a topic of interest as researchers find it is able to use regular body fat as fuel and exercise may stimulate hormones that activate it. Now, a new study by UT Southwestern (UTSW) Medical Center scientists demonstrates that boosting a protein found in BAT lowers blood sugar, promotes insulin sensitivity, and protects against fatty liver disease by remodeling white fat to a healthier state.

Their study is published in an article in Nature Communications, titled “Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance.” Their findings may eventually lead to new therapeutic options for type 2 diabetes (T2D) and metabolic-related conditions.

“Exposure of mice or humans to cold promotes significant changes in BAT with respect to histology, lipid content, gene expression, and mitochondrial mass and function. Herein we report that the lipid droplet coat protein Perilipin 5 (PLIN5) increases markedly in BAT during exposure of mice to cold.”

“By taking advantage of this natural system, we may be able to help make fat depots more metabolically healthy and potentially prevent or treat obesity-associated diabetes,” explained study leader Perry E. Bickel, MD, associate professor of internal medicine at UTSW.

The researchers genetically engineered mice that made extra PLIN5 in BAT. The animals maintained significantly lower blood sugar concentrations and higher insulin sensitivity during glucose tolerance tests, compared with mice with normal PLIN5 levels.

They also found that the BAT’s mitochondria in the genetically engineered mice had adapted to burn even more fat, similar to what’s seen in animals placed in cold temperatures. Upon closer observation, the researchers discovered that the white adipocytes of animals that had extra PLIN5 in their brown adipocytes were smaller and had reductions in some markers of inflammation, which are changes that are associated with improved sensitivity to insulin and metabolism of sugar.

“The next question we want to address,” said Bickel, “is what that factor is and whether we can harness it for therapeutic benefit.”

“The idea that human brown or beige adipose tissue is a promising target for the development of therapeutics to address type 2 diabetes is reinforced by our finding that increasing PLIN5 in mouse BAT promotes glucose tolerance, healthy remodeling of iWAT, and protection against hepatic steatosis on a high-fat diet (HFD),” write the researchers. “We have shown that more PLIN5 in brown adipocytes augments mitochondrial oxidative function, and promotes the uptake and oxidation of fatty acids in BAT…Our studies reported here suggest the potential of PLIN5 to mimic the effect of cold temperature on BAT and, thereby, to improve systemic glucose tolerance and protect against diet-induced hepatic steatosis.”

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