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Brown fat

Mechanism for brown fat regulation discovered

Findings may lead to new therapies to treat obesity
lead author of the study Dr Yu-Hua Tseng

Researchers at Joslin Diabetes Center have discovered a mechanism that regulates the production of brown adipose tissue (BAT or brown fat), which plays an important role in heat production and energy metabolism. The findings, which appear in the journal Nature, could lead to new therapies that increase brown fat formation to treat obesity.

“These data suggest an important physiological cross-talk between constitutive and recruitable brown fat cells,” said lead author of the study Dr Yu-Hua Tseng, assistant professor of Medicine at Harvard Medical School. “This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease. This new type of therapy would be especially beneficial to individuals who cannot lose weight through diet or have a limited ability to exercise.”

Previous studies have shown that brown fat provides a natural defence against obesity by metabolising glucose and fatty acids, crucial in the development of diabetes and metabolic diseases.

Joslin researchers have already established that that one type of bone morphogenetic protein - BMP-7 - plays a key role in the control of brown fat formation.

For this study, the researchers created a genetically mutant mouse model deficient in type 1A BMP-receptor (BMPR1A), a key receptor for BMP-7. Mice are known to have two types of BAT: constitutive BAT (cBAT), which develops before birth; and recruitable BAT (rBAT), which is found in WAT and skeletal muscle. The mice lacking BMPR1A were born with a deficiency of cBAT.

Despite the lack of cBAT, the mutant mice were able to maintain their body temperature perfectly. The researchers discovered that when cBAT is deficient, cBAT cells send a signal through the sympathetic nervous system to increase production of rBAT within white fat. The increased rBAT was sufficient to maintain normal body temperature and also protect against diet-induced obesity. When the control and mutant mice were fed a high-fat diet, the mutant mice did not gain more weight than the control mice.

Tseng said that future research will examine the function of human brown fat cells, including whether humans have two types of BAT, and understanding how BMP and related factors affect human brown fat production.

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