Mechanisms of Innate Immune Modulation by High-Fat Diet: Implications for Obesity and Asthma

The innate immune system plays a critical role in mediating many of the physiological consequences of high-fat diet consumption. Dietary lipids, and specifically saturated fatty acids like palmitate and stearate, directly activate innate immune cells and alter the composition of the gut microbiome. Moreover, long-term high-fat diet feeding can induce chronic inflammation, adipose expansion, and the development of obesity. High-fat diet consumption and obesity also worsen the risk for chronic diseases like asthma.

It is well known that high-fat diet feeding activates innate immune cells and alters the gut microbiome. However, emerging research provides new insight into the mechanisms by which high-fat diet feeding and obesity affect innate immunity and further disease development. These emerging mechanisms include the induction of lipid-associated macrophages (LAMs), innate immune memory, and innate-adaptive crosstalk leading to T cell exhaustion and granzyme K production. These novel mechanisms help us better understand the effect of high-fat diets on innate immunity, and future studies in these areas may help us better identify new therapeutic strategies for managing obesity and asthma.