The immune system is composed of many cells that defend the body against various pathogens. Macrophages are cells of the immune system that are best known for their ability to “eat” big particles, a phenomenon called phagocytosis. It is actually with this function that they earned their Greek name “big eaters” (Macro-Phage). In a situation of inflammation (e.g. injury, infection), while removing pathogens, macrophages also produce signals called inflammatory cytokines that alert the rest of the immune system. Subsequently, in order to resolve the inflammatory response, macrophages clear dead cells and produce growth factors and anti-inflammatory cytokines important in the healing process. In this regard, macrophages can have both pro-inflammatory and anti-inflammatory functions. Macrophages have been mostly studied in the context of inflammation, but more recently in the past 2 decades, their role in metabolism has come to light. They were the first immune cells to be described during the emergence of a new field, called immunometabolism, which investigates the cross-talk between immune cells and metabolic cells. The Aouadi lab focuses on the contribution of macrophages to metabolic diseases.
Obesity is a condition characterized by an excessive expansion of fat, termed adipose tissue. The prevalence of obesity is increasing rapidly both in westernized and developing countries. While obesity represents a high-risk factor for many serious illness, such as cancer, heart failure, and diabetes, it is often misconstrued to be an aesthetic issue rather than a major health concern. Obese patients can experience weight bias and stigma in media, schools, workplaces, and even in health care settings. This is because their condition is often aberrantly assumed to be a result of their unwillingness to eat less or to engage in a more active life style, rather than a problem of biological origin. The failure of health care systems in decreasing the rate of obesity is the first hint that life style intervention to lose weight and maintain it does not work. Many research groups have shown that the reason for this failure is the fact that these interventions often overlook the importance of genetic and epigenetic predispositions, which relate to information that is inherited or induced by the environment.
In the Aouadi lab we investigate the mechanisms involved in the development of diabetes and liver disease in obese patients. In a healthy individual, the pancreas produces insulin, a hormone that regulates the amount of glucose in the blood after a meal. However, especially in obese patients, a condition termed insulin resistance occurs before overt diabetes. This is a condition in which the body cannot respond to insulin and therefore produces high levels of insulin to compensate. Despite this compensation, glucose is still not properly metabolised. For instance, the adipose tissue cannot properly take up glucose and store it in forms of fat, which results in lipid accumulation in other organs, such as the liver. Fat accumulation in the liver is toxic and can lead to a disease called Non-Alcoholic SteatoHepatitis (NASH).
NASH is projected to become the leading cause of liver related morbidity and mortality within 20 years, and the most common indication for liver transplantation in the next few years. In spite of its high prevalence and potential life-threatening effects, no approved treatments are currently available due to a lack of understanding of the pathogenesis. Epidemiological studies show that individuals with obesity and insulin resistance are at the greatest risk of developing NASH. However, the underlying mechanisms causing liver disease in individuals with metabolic disorders such as obesity and insulin resistance remain unknown.
Our lab has discovered that macrophages in the liver and adipose tissue are crucial in the development of metabolic dysfunction in these tissues independently of their inflammatory profile. Our lab takes advantage of sophisticated methods to investigate the multiple roles of macrophages and their function in obesity-associated metabolic dysfunction. To learn more about our research, check out our specific projects or contact us!
The group is part of CIM at Karolinska Institutet: Aouadi Lab at Karolinska Institutet
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