Study Explores Role of Macrophages in Obesity

Obesity_Remi BENALI/Gamma-Rapho via Getty Images

Remi BENALI/Gamma-Rapho via Getty Images

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States in 2017-2018 was 42.4%. Research on obesity is essential, as the condition can lead to serious health consequences, such as heart disease, stroke, Type II Diabetes and certain types of cancer. Researchers are now turning to the immune system for answers about the condition.

A team of researchers from the Boston University School of Medicine recently studied mice models of obesity, taking a special interest in macrophages. Macrophages are specialized immune cells involved in detecting and destroying bacteria and other foreign invaders in the body. Macrophages are often found within fat or adipose tissue, making them a target of interest to researchers interested in obesity.

Researchers discovered that macrophages in models of obesity become senescent, meaning that the cells permanently stop dividing but do not die. In healthy individuals, macrophages contribute to cleaning tissue from dead adipocytes or cells specialized in fat storage, helping in cellular turnover. In obese animal models, macrophages lose this ability, contributing to fat tissue fibrosis or fat accumulation. 

In addition to accelerating fat accumulation, these macrophages also secrete various pro-inflammatory factors such as osteopontin. Osteopontin is implicated in a variety of chronic inflammatory diseases, and the researchers found that it was responsible for adipose tissue fibrosis. Combining these results, the team proposes that targeting senescent macrophages or using osteopontin inhibition could be used as an approach for obesity treatment and adverse complications of obesity, such as Type II Diabetes.

In their research publication, the authors state that dysfunctional macrophages promoted by obesity may also play a role in the inability of the body to return to homeostasis after injury or an inflammatory reaction and could promote a favorable environment for chronic disease. Additionally, the authors cite that senescent immune cells, including macrophages, have been found to play a role in the pathogenesis of other severe diseases, including Alzheimer’s, osteoporosis, cancer, and atherosclerosis.

These results add to the growing field of research concerning how obesity impacts the immune system. Another immune process impacted by obesity is autophagy, or the process by which a body cleans out damaged cells in order to regenerate new and healthy cells. Autophagy is also essential for the regulation of the cell’s responses to different stresses and functional states and constitutes an important pathway for the generation of an immune response. Obesity can influence autophagy negatively, hindering the immune system’s ability to defend the body against pathogens and infection.

For example, having obesity increases the risk of severe illness from COVID-19 and may triple the risk of hospitalization. Researchers dedicated to understanding this connection have stated that in individuals who are obese, the fat tissue becomes unhealthy, leading to the secretion of hormones and chemical signals that promote chronic low-grade inflammation, which can impair the immune system’s response to infection and create further chaos when infection ensues.

Although there is much research to support the immune system targeting treatments for obesity in humans, there are currently no therapeutics in clinical trials. Instead, current guidelines for promoting good immune system health in obese individuals include eating a healthy diet, being active, getting enough sleep, and improving coping skills for stress.

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