Phenotypic Switch of Adipose Tissue Macrophages as a Target to Reduce Obesity-Associated Metabolic Risk

Obesity, a chronic inflammatory disease, is caused by a positive balance between energy intake and energy expenditure. Adipose tissue (AT) inflammation is the main cause of local and systemic inflammation and oxidative stress and is the link between systemic inflammation and obesity-associated metabolic abnormalities, such as dyslipidemia, hypertension, insulin resistance (IR), fatty liver disease, and dysfunction of pancreatic β-cells. AT macrophages are derived from bone marrow and blood monocytes that, upon arrival and under the pressure of the AT microenvironment, are differentiated into AT-associated macrophages (ATMs). The AT microenvironment in obesity causes the activation of transcription factors that control the expression of a number of inflammatory genes, leading to an ATM M1 phenotype or classically activated ATM. These M1 macrophages express a number of proinflammatory genes and are the main cause of AT inflammation. Herein, we reviewed recently published information on the molecular mechanisms leading to the phenotypic switch of macrophages under the pressure of obese AT. This information is needed to develop novel mechanism-based therapeutics to reduce AT inflammation and thus the metabolic risk associated with obesity.