Scope: Insulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL-1β inflammation and IR. Interactions between SFA intake and NLRP3-related genetic variants may alter T2D risk factors. Methods: Meta-analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3-related single-nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance. Results: SFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL−1 (SE ± 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (β ± SE = −0.0058 ± 0.002, p = 0.004) to increase insulin by 0.0058 IU mL−1, per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression. Conclusion: Two NLRP3-related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3-related genetic variants.

Additional Metadata
Keywords Cohorts for Heart and Ageing Research in Genomic Epidemiology consortium, genome-wide interaction studies, insulin resistance, meta-analyses, NLRP3 inflammasomes, saturated fats
Persistent URL dx.doi.org/10.1002/mnfr.201900226, hdl.handle.net/1765/120429
Journal Molecular Nutrition & Food Research (Print)
Citation
Murphy, A.M. (Aoife M.), Smith, C.E, Murphy, L.M. (Leanne M.), Follis, J.L, Tanaka, T. (Toshiko), Richardson, K. (Kris), … Roche, H.M. (Helen M.). (2019). Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta-Analysis of 19 005 Individuals. Molecular Nutrition & Food Research (Print). doi:10.1002/mnfr.201900226