Palmitic Acid Activation of Dendritic Cells: Implications for Type 2 Diabetes
Infiltration of immune cells into visceral adipose tissue is observed in type 2 diabetes development. Monocytes are recruited to obese visceral adipose tissue in large numbers and retain the ability to differentiate into dendritic cells, important antigen presenting cells in the immune system. Differentiation of monocytes into dendritic cells likely accounts for the increased number of dendritic cells observed in the adipose tissue of type 2 diabetic patients. We have demonstrated this differentiation process is regulated in part by a major reduction of linker histone proteins. In adipose tissue, dendritic cells are exposed to high levels of saturated fatty acids. Increased saturated fatty acid levels derived from high fat diets are strongly associated with chronic adipose tissue inflammation. Palmitic acid, the most abundant of saturated fatty acids, is pro-inflammatory and has been linked to insulin resistance. However, the mechanisms underlying palmitic acid induction of inflammation remain unknown. We have confirmed palmitic acid binding to Toll-like receptor 4 (TLR4) on human dendritic cells. In response to palmitic acid activation of TLR4, dendritic cells were shown to secrete pro-inflammatory cytokines that may lead to insulin resistance. In addition, we identified anti-palmitic acid IgG antibodies in the serum of patients with unmanaged type 2 diabetes. In conclusion, diet-derived saturated fatty acids may act as mediators of chronic inflammation associated with type 2 diabetes. Together, the experimental data presented support the hypothesis that palmitic acid is an inducer of dendritic cell induced inflammation and is an important target for type 2 diabetes therapy.
Biochemical Phenomena, Metabolism, and Nutrition, Medical Biochemistry, Adipose Tissue - Cytology; Antigen-Presenting Cells; Dendric Cells; Diabetes Mellitus - Type 2; Diet - High Fat; Dietary Fats; Fatty Acids; Inflammasomes; Insulin Resistance; Macrophage Inflammatory Proteins; Palmitic Acid; Toll-Like Receptors, Immune cells; Monocytes; Linker Histone Proteins; Chronic Adipose Tissue Inflammation;
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