The Role of Meta-Inflammation in The Adipose Tissue Dysfunction and Obesity

The term “meta-inflammation” refers to chronic metabolic inflammation, which is thought to have an important role in the pathogenesis of numerous metabolic diseases. Majority of authors agree that inflammation, as a component of immune system, may serve as a link between obesity and numerous diseases. Hence, the role of meta-inflammation in the pathogenesis of obesity-related diseases is extensively investigated. Mitochondrial dysfunction in adipocytes is lately regarded as a primary cause of adipose tissue inflammation. This newly proposed hypothesis contradicts currently prevailing concept that “adipose tissue hypoxia” underlies adipose tissue dysfunction in obesity. Infiltration of adipose tissue by immune cells is one of the hallmarks of adipose tissue dysfunction. Based on the current knowledge, adipose tissue (AT) macrophages are considered to have a pivotal role in the development of adipose tissue inflammation and dysfunction. Macrophages that infiltrate the adipose tissue are divided into: pro-inflammatory (M1) and anti-inflammatory (M2) AT macrophages. Studies have shown that M1 AT macrophages contribute to insulin resistance by producing pro-inflammatory cytokines. Conversely, M2 AT macrophages are involved in the repair or remodeling of tissues. In obesity, adipose tissue becomes inflamed and goes through cellular remodeling. Adipocytes increase in number (hyperplasia) and size (hypertrophy), become infiltrated by macrophages and undergo fibrosis. Hypertrophic adipocytes secrete more pro-inflammatory molecules that lead to a shift of M2 to M1 AT macrophages. Adipose tissue dysfunction in obesity is characterized by changes on cellular and molecular level, which include immune cells such as T cells, B cells and dendritic cells. However, their role in meta-inflammation and adipose tissue dysfunction remains to be fully elucidated. Novel findings suggest that dysregulation of autophagy in adipose tissue has an important role in metainflammation. Studies have shown that there is a strong relationship between the prenatal and perinatal environment and obesity-related diseases. Childhood obesity is associated with meta-inflammation that affects not only adipose tissue but other organs as well. Since adipose tissue dysfunction in obesity plays a pivotal role in disturbing homeostatic processes in the human body, it is of essential importance that health care systems at the global level work on implementation of precautionary strategies in order to prevent the development and progression of meta-inflammation and obesity-related metabolic complications starting at early stages of life.

Keywords: Adipose tissue dysfunction, Adipose tissue dendritic cells, Antiinflammatory cytokines, Autophagy, B cells, Macrophages, Macrophage polarization, Meta-inflammation, Obesity, Pro-inflammatory cytokines, T regulatory cells.