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Kinase and obesity

Protein kinase is the switch controlling obesity and diabetes

The results could have potential clinical implications for the treatment of obesity and related diseases like diabetes

Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have uncovered the mechanism by which brown fat cells are activated to generate heat and eliminate excess fat. The results could have potential clinical implications for the treatment of obesity and related diseases like diabetes.

The study, ‘p38α blocks brown adipose tissue thermogenesis through p38δ inhibition’, published in PLoS Biology, led by Dr Guadalupe Sabio and in collaboration with the Instituto de Investigación Biomédica de Salamanca (IBSAL) and Salamanca University Hospital, identified a new mechanism with future clinical applications. In more than 150 human samples, the researchers have demonstrated that the protein kinase p38 alpha is more abundant in the adipose tissue of obese individuals.

According to researcher Nuria Matesanz, the finding suggested that "p38 alpha may regulate UCP1, an important protein for brown fat activation that dissipates the energy generated from burning excess fat as heat."

Thermographic image illustrating that mice lacking p38 alpha in adipose tissue do not gain weight when fed a high-fat diet and generate more heat (white areas) due the activation of brown fat. Credit: CNIC

In experiments with mice genetically modified to lack p38 alpha, the research team found that the absence of this protein in adipose tissue prevents the mice from becoming obese even when fed a high-fat diet. This protection, explained research team member Ivana Nikolic, "is due to the fact that the lack of p38 alpha activates brown adipose tissue, which eliminates excess white fat in the form of heat." Just as important, the study shows that mice lacking p38 alpha are protected against diabetes and fatty liver disease.

"These results suggest that pharmacological inhibition of p38 alpha could offer a route to the treatment of obesity,” said Dr Sabio.

The study also reveals another important finding: p38 alpha controls the activation of another protein of the same family, p38 delta, which is responsible for temperature regulation. The authors explained, "When mice are exposed to low temperatures, p38 delta is activated, increasing the activity of brown fat." In mice lacking p38, p38 delta is overactivated, resulting in protection against obesity.

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