Brown adipose tissue (BAT) plays a critical role in thermogenesis, converting fat into heat, thus providing protection against obesity, type 2 diabetes, and cardiovascular diseases. A recent study led by the University of Barcelona has uncovered a key molecular process involved in the decline of BAT activity as the body ages. This discovery paves the way for new strategies aimed at enhancing BAT function and preventing chronic metabolic and cardiovascular conditions in an aging population.
The research, published in Science Advances, is spearheaded by Professor Joan Villarroya from the Faculty of Biology and the Institute of Biomedicine at the University of Barcelona, alongside collaborators from the Albert Einstein College of Medicine in New York. The study focuses on the role of chaperone-mediated autophagy (CMA), a cellular process that selectively degrades specific proteins, in regulating BAT activity.
As organisms age, the efficiency of CMA diminishes, leading to reduced BAT activity. “Acting on chaperone-mediated autophagy may play a key role in modulating the tissue activity,” states Professor Villarroya. The research indicates that CMA is responsible for the degradation of proteins that repress thermogenic activity, thus facilitating BAT functionality.
Efforts to design drugs that activate BAT have historically been hindered by adverse side effects. However, Professor Villarroya notes that effective experimental drugs are now emerging, capable of modulating CMA. In trials involving aging mice, these drugs maintained BAT activity and improved metabolic function despite advancing age.
Preclinical drugs initially developed for neurodegenerative diseases show promise in activating CMA. Clinically, these compounds could potentially prevent BAT inactivation in aging populations or in individuals with obesity or diabetes, where low BAT activity poses significant risks.
The research team is actively exploring how CMA can be harnessed to enhance metabolic energy expenditure, aiming to control obesity and its cardiometabolic consequences. These investigations are being pursued in both experimental models and early-stage patient studies, in collaboration with several hospitals.
