Abstract
The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases.
Highlights
The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1 release
In human primary monocytes primed with LPS to increase expression of both NLRP3 and pro-IL-1 (Fig. 1A, bottom), we showed that stearate (C18:0) was able to induce IL-1 release with similar efficiency as palmitate when compared with vehicle alone (BSA) (Fig. 1A, top)
Oleate (C18:1) and linoleate (C18:2) had no effect on IL-1 secretion, showing opposite effects of saturated fatty acid (SFA) compared with unsaturated fatty acid (UFA)
Summary
The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1 release. We reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1 secretion in a caspase-1/ASC/NLRP3-dependent pathway. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, IL-1 processing. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages. A second stimulus is required to induce NLRP3 inflammasome assembly, caspase-1 activation, and, IL-1 maturation
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