Could brown fat macrophages help in tackling metabolic disorders?Obesity and the diseases related to it have increased globally. The obesity-associated inflammation is mainly caused by immune system cells known as macrophages that reside in white body fat. On the other hand, brown body fat is known to be beneficial to our health, but its mechanisms of action are still largely unexplored.
Writer: Heli Jokela
It is known that macrophages residing in white body fat (white adipose tissue, WAT) are the main cause of the obesity-associated inflammatory state. Macrophages are ‘scavengers’, that is, immune system cells that destroy pathogens and other harmful particles. These tissue-specific macrophages interact with fat cells (adipocytes) and contribute to the pathogenesis of various metabolic diseases associated with obesity, such as Type 2 diabetes and atherosclerosis.
Unlike WAT, which stores fat, brown adipose tissue (BAT) burns calories and enhances lipid metabolism. Accordingly, brown fat is beneficial for, among other things, blood sugar (glucose) metabolism and weight management, and it also lowers the level of the ‘bad’ cholesterol in the body.
According to current knowledge, adults have deposits of brown fat that is activated, for example, when we are exposed to cold temperatures. The health benefits of brown fat have been demonstrated by researchers, but our knowledge about the BAT immunology is still limited. The known health benefits of brown fat inspired me to explore the possibility of treating or even preventing obesity and diabetes through the modification of BAT resident macrophages.
The development of optimal therapeutic methods requires fundamental scientific knowledge about the origin and evolution of macrophages, as well as the mechanisms to maintain their homeostasis. The purpose of my research is to investigate the origin of brown adipose tissue-specific macrophages, analyse the role of macrophages in the development and functioning of brown fat and to explore the ways in which the activation or inhibition of macrophages of different origins could be used to activate brown fat to help protect our bodies against obesity.
Similar cells derive from different sources
In addition to defending our bodies as part of the immune system, tissue-specific macrophages are involved in the evolution of the particular tissues and maintenance of their homeostasis. Moreover, they play a role in pathological conditions, such as in the development of cancer.
In mice, the tissue-specific macrophages derive from three different sources: from the yolk sac and liver during the embryonic development phase and, after birth, from the monocytes (a type of immune cell) produced in the bone marrow. They are transported by blood circulation to the various tissues to differentiate into tissue-specific macrophages.
In adults, all tissues feature a unique collection of these macrophages of different origins. Our general hypothesis is that the origin will define the function of different macrophages and, in particular, their response under different conditions, such as obesity. This is true for brown fat as well: the BAT macrophages are either pro- or anti-inflammatory depending on their origin. Inês Félix, a doctoral candidate under my supervision, and I myself have studied macrophages by using single-cell sequencing techniques and the latest imaging technologies at Turku Bioscience. Currently, we are investigating, in particular, the functions of those macrophages that are developed during the embryonic phase and their role in the development and functioning of brown fat in adulthood.
A focus on the development of new treatments
This research is aimed at finding methods to prevent the inflammatory responses of macrophages in brown fat by means of modifying the macrophages. On the other hand, the activation of BAT by boosting the functioning of anti-inflammatory macrophages would open entirely new opportunities to improve, for example, glucose balance in the body. The support granted by the Sakari Alhopuro Foundation provides a solid base for my research project, which aims at investigating the potential offered by BAT macrophages for the development of new immunological therapies. We hope for the research results to bring about concrete help in terms of the treatment of patients suffering from diabetes and metabolic disorders.
PhD Heli Jokela is working as a Senior Researcher in the research group led by Pia Rantakari at Turku Bioscience (previously known as the Turku Centre for Biotechnology). She earned her doctoral degree in 2018 from the University of Turku, Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology. The Rantakari Group is part of the Academy of Finland Flagship Programme InFLAMES.