Obesity is a complex metabolic disorder characterized by an excess accumulation of adipose tissue. It is a global public health problem that affects both children and adults.

The prevalence of obesity has more than doubled worldwide in the past few decades. Obesity is associated with increased morbidity and mortality, as well as increased healthcare costs.

Obesity is associated with a low-grade systemic inflammation that has been linked to the development of insulin resistance, type 2 diabetes, cardiovascular disease, and other metabolic disorders. In this article, we will discuss the immune system dysregulation seen in obesity and its implications.

Adipose tissue as an endocrine organ

Adipose tissue is an endocrine organ that releases several hormones and cytokines. Adipocytes secrete adipokines, which are involved in regulating glucose and lipid metabolism, inflammation, and insulin sensitivity.

Adiponectin, an adipokine that is predominantly secreted by adipocytes, has anti-inflammatory and insulin-sensitizing properties. However, the secretion of adipokines is dysregulated in obesity, leading to low-grade inflammation.

Immune system dysregulation

Obesity is associated with the infiltration of immune cells into adipose tissue. The immune cells in adipose tissue include macrophages, T cells, B cells, and natural killer cells. Macrophages are the most abundant immune cells in adipose tissue.

In obesity, adipose tissue becomes hypoxic, leading to the secretion of chemokines, which attract macrophages. The infiltrating macrophages differentiate into two subtypes based on their phenotype. M1 macrophages release pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, leading to chronic inflammation.

M2 macrophages have anti-inflammatory properties and are involved in tissue repair. In obesity, there is an imbalance between M1 and M2 macrophages, leading to a pro-inflammatory state.

T cells and B cells are also present in adipose tissue. CD4+ T cells differentiate into T helper 1 (Th1) and T helper 2 (Th2) cells.

Th1 cells produce pro-inflammatory cytokines, such as IFN-γ and TNF-α, while Th2 cells produce anti-inflammatory cytokines, such as IL-10. In obesity, there is an imbalance between Th1 and Th2 cells, leading to a pro-inflammatory state. B cells produce antibodies and play a role in the adaptive immune response.

In obesity, there is an increase in the number of B cells in adipose tissue, which may contribute to the chronic inflammation seen in obesity.

Implications of immune system dysregulation

The dysregulation of the immune system in obesity has several implications. Chronic inflammation plays a role in the development of insulin resistance, type 2 diabetes, and cardiovascular disease.

Inflammation also contributes to the development of non-alcoholic fatty liver disease. In addition, chronic inflammation may contribute to the development of cancer.

Therapeutic approaches

Therapeutic approaches for the dysregulation of the immune system in obesity are being developed. These approaches include targeting inflammatory cytokines, such as TNF-α.

Anti-TNF-α therapy has been shown to improve insulin sensitivity and reduce inflammation in obese individuals. Another approach is to target the infiltration of immune cells into adipose tissue. One study showed that blocking the chemokine receptor CCR2 decreased macrophage infiltration and improved insulin sensitivity in obese mice.

In addition, lifestyle interventions, such as weight loss and exercise, have been shown to improve immune function in obese individuals.

Conclusion

Obesity is associated with immune system dysregulation, leading to chronic inflammation and metabolic dysfunction. The dysregulation of the immune system in obesity has several implications for health.

Therapeutic approaches are being developed to target the dysregulation of the immune system in obesity. Lifestyle interventions, such as weight loss and exercise, can also improve immune function in obese individuals.