Researchers in the UNC Gillings School of Global Public Health have found that it is possible to control inflammation in fat tissue by manipulating the presence of a specific metabolic protein in a type of white blood cell called a macrophage. This metabolic reprogramming may provide a crucial strategy for weakening the link between obesity and illnesses such as diabetes.
This research is the topic of a new study by the lab of Dr. Liza Makowski, assistant professor of nutrition at UNC’s Gillings School and lead author of the paper about the findings. The researchers examined a fatty acid transporter protein that has never been studied before in connection to macrophages.
[Photo: Dr. Liza Makowski]
The full article, “Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation,” was published online April 23 in Molecular Metabolism.
Macrophages can be recruited into tissue in response to stress signals such as the presence of bacteria or defective cells. However, they also enter into fat tissue, or adipose tissue, in response to stress from obesity. By triggering macrophage infiltration, obesity causes a chronic inflammatory response that can lead to dire health consequences like diabetes.
As macrophages continually respond to the obese state, they can eventually comprise up to 50 percent of the cells in adipose tissue. Accordingly, understanding how macrophages function, and determining whether their actions can be controlled, is of critical importance to obesity research.
In this study, the researchers showed that by opening or closing the door to certain fatty acids by increasing or eliminating the presence of Fatty Acid Transport Protein 1 (FATP1), they could alter the standard macrophage inflammatory response. In particular, they demonstrated that when FATP1 was absent, inflammation in fat tissue increased.
Additionally, research showed that obese mice with macrophages lacking FATP1 gained more weight and had higher blood glucose levels while obese. This finding suggests that, without FATP1 availability, the mice developed glucose dysregulation.
This dysregulation occurred because, when macrophages could not access FATP1, the cells switched from using fatty acids as a fuel source to using glucose. This change caused an increase in inflammation, a reaction that can lead to diabetes. On the other hand, when researchers exposed macrophages to extra levels of FATP1, the cells utilized fuel from fatty acids rather than glucose and became less responsive to inflammation – an effect that could slow or prevent the development of diabetes.
Using large databases, the researchers also discovered gene variants in FATP1 that are associated with how the protein is expressed in human adipose tissue. In the future, studies using human white blood cells will be necessary to determine whether these genetic variants have effects specific to human macrophage biology and disease.
“Macrophage inflammation and metabolism has been the topic of much debate in the field,” Dr. Makowski said. “It is a bit of a ‘which came first: the chicken or the egg?’ [dilemma]. We are excited to show that through first changing cellular metabolism, we can then alter the macrophage inflammatory response. This opens the door to many new possibilities for controlling inflammation in the human body.”
Co-first authors of the paper are Dr. Amy R. Johnson, former postdoctoral fellow, and Dr. Yuanyuan Qin, former graduate student, both with the Department of Nutrition at UNC Gillings. Other study co-authors affiliated with the Gillings School include Ms. Alyssa J. Cozzo, doctoral student, Dr. Alex J. Freemerman, research associate, Ms. Megan J. Huang, undergraduate alumna, Ms. Liyang Zhao, doctoral student, Dr. Brante P. Sampey, former postdoctoral fellow, Dr. J. Justin Milner, alumnus, and Dr. Melinda A. Beck, professor, all with the nutrition department. Dr. Naim Rashid is a research assistant professor in the UNC Gillings School’s Department of Biostatistics.