Leptin in the regulation of the immunometabolism of adipose tissue‐macrophages

Obesity is a pandemic disease affecting around 15% of the global population. Obesity is a major risk factor for other conditions, such as type 2 diabetes and cardiovascular diseases. The adipose tissue is the main secretor of leptin, an adipokine responsible for the regulation of food intake and energy expenditure. Obese individuals become hyperleptinemic due to increased adipogenesis. Leptin acts through the leptin receptor and induces several immunometabolic changes in different cell types, including adipocytes and M phi s. Adipose tissue resident M phi s (ATMs) are the largest leukocyte population in the adipose tissue and these ATMs are in constant contact with the excessive leptin levels secreted in obese conditions. Leptin activates both the JAK2-STAT3 and the PI3K-AKT-mTOR pathways. The activation of these pathways leads to intracellular metabolic changes, with increased glucose uptake, upregulation of glycolytic enzymes, and disruption of mitochondrial function, as well as immunologic alterations, such as increased phagocytic activity and proinflammatory cytokines secretion. Here, we discuss the immunometabolic effects of leptin in M phi s and how hyperleptinemia can contribute to the low-grade systemic inflammation in obesity.