Substituting dietary monounsaturated fat for saturated fat lowers inflammasome activation observed on a high saturated fat diet

Abstract

Altered lipid homeostasis (obesity) is linked to inflammation and defective insulin signaling. In the presence of palmitic acid (PA), but not oleic acid (OA), lipopolysaccharide (LPS)‐stimulated macrophages activate the NLRP3 inflammasome, secreting augmented levels of Interleukin (IL)‐1β and IL‐18 (Nat Immunol12:408). We hypothesized that lowering the PA/OA ratio of the PA‐rich, Western Diet would alter cytokine secretion from peripheral blood mononuclear cells (PBMC) harvested from 14 fasted, young adults (8 men/6 women), enrolled in a randomized, double‐masked, cross‐over trial comparing two 3‐week diets: (1) high PA (HPA), with a fatty acid pattern resembling their habitual diet; (2) low PA/high OA (HOA). Immediately after collection, PBMC were stimulated with 1 ng/ml LPS for 24 hr, and cytokines were measured. Log (base 10) transformed data, corrected for baseline values on a low fat diet, revealed that IL‐1β (P = 0.029), IL‐18 (P = 0.037), IL‐10 (P = 0.02), and Tumor Necrosis Factor‐1α, (P = 0.039) were higher during HPA, compared to HOA. These data suggest that, in healthy adults, the higher than recommended PA intake of the Western Diet facilitates augmented secretion of several cytokines, including those regulated by inflammasome activation. (Support: NIDDK: R01‐DK 082803).