Impact of Dietary Fatty Acids on Macrophage Lipid Metabolism, Signaling and Function

Abstract Leukocytes are potent regulators of adipose tissue biology and whole-body metabolic homeostasis. In lean, non-obese conditions (insulin-sensitive), adipose tissue has innate and adaptive immune cells, including eosinophils, regulatory T cells, invariant NK cells, and M2 macrophages. A vast expansion in adipose tissue occurs in obesity, and this is associated with a marked alteration in the tissue leukocyte profile. There is a marked increase in B cells, CD8+ T cells, NK cells, neutrophils, and M1 macrophages. This condition induces a state of low-grade, chronic inflammation in the adipose tissue, which disrupts whole-body metabolism. Macrophages were the first leukocyte to be discovered in adipose tissue. Due to their proximity to nearby adipocytes, the macrophages are exposed to high levels of fatty acids and other lipids reported in obesity. Lipid uptake by tissue-resident macrophages is essential for their biological actions. Specifically, lipid uptake and metabolism, particularly of long-chain saturated fatty acids, activate inflammatory signaling pathways, potentiating adipose tissue inflammation, and metabolic dysfunction. Obesity exhibits increased fatty acid levels within the adipose tissue microenvironment. The increased lipid accumulation in the resident macrophages reflects the fatty acid composition of the adipocytes. The dietary fatty acid determines the fatty acid composition of the adipose tissue. Macrophages then accumulate fatty acids indirectly provided by the diet. The composition varies with the acyl chain length, e.g., short-, medium-, or long-chain, and saturated fatty acids. These fatty acids have wide-ranging effects on macrophages. We described herein in detail the impact of the different dietary fatty acids on macrophage functions. Shortly, long-chain saturated fatty acids are pro-inflammatory, whereas medium-chain fatty acids are relatively benign. Long-chain unsaturated fatty acids often antagonize the pro-inflammatory effects of long-chain saturated fatty acids.