Obesity, diabetes and cardiovascular diseases are increasingly present in the population. Brown adipose tissue has a protective function against these prevalent diseases, as it burns calories and can produce body heat from fat. But as the body ages, the activity of brown adipose tissue decreases. This inactivation of brown adipose tissue — also typical of obese people — remains poorly studied in the scientific literature.
Now, a study by the University of Barcelona has identified, for the first time, a molecule that represses the activity of brown adipose tissue. The paper opens new paths to understand why and how the inactivation of this key tissue for metabolizing fat in the body takes place, and especially to determine wether this repressor function can be reversed and help design strategies for the treatment of obesity and cardiometabolic diseases.
The study, published in Molecular Metabolism, is led by Professor Francesc Villarroya, from the UB’s Faculty of Biology and the UB Institute of Biomedicine (IBUB) — headquartered at the Barcelona Science Park (PCB) —, Sant Joan de Déu Research Institute (IRSJD) and the CIBER area for Pathophysiology of Obesity (CIBEROBN). The article is the core of the research of the doctoral thesis of the expert Albert Blasco Roset, first author of the paper and doctoral student at the UB.
Shifting perspectives: beyond the activators
There are two types of adipose tissue in the body: white adipose tissue (it stores energy in the form of lipids) and brown adipose tissue (the main heat-generating organ in the body through thermogenesis).
“Although the problem is to know what reduces the activity of brown fat, until now, research has focused on identifying the factors that activate its function in the organism, but not the factors with a repressive function”, says Francesc Villarroya, a member of the Department of Biochemistry and Molecular Biomedicine at the Faculty of Biology.
“As a result, it was generally assumed that the low activity of brown fat in ageing and obesity could be explained by the fact that its activators do not work properly”.
The new study, conducted in animal models, describes a repressor factor that blocks brown fat activity: the ACBP protein. Under normal conditions, this protein would regulate when brown fat activity is not needed (e.g. in a warm environment). However, this molecule would also be involved in ageing and in the pathological blocking of brown adipose tissue that leads to obesity.
Why does climate change increase obesity?
The ACBP protein’s control activity reveals further biomedical implications in the fight against diseases such as cancer. “In some cancers, brown adipose tissue becomes pathologically overactive and causes uncontrolled metabolic energy expenditure, leading to cachexia (extreme malnutrition and muscle wasting). In this case, the function of the ACBP protein as a repressor factor could become a therapeutic tool of interest in cancer patients”, says Villarroya.
In another context, it is also known that global warming caused by climate change is contributing to rising obesity rates, as an increasingly warmer environment leads to inactive brown adipose tissue. “An excess action of the ACBP protein blocking the activity of brown fat would be the molecular basis of this phenomenon. Once this factor has been identified, we can design intervention tools to promote a healthier lifestyle”, concludes the researcher.