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
Lkram MA; Raitakari OT; Noordam R; Smith CE; Richardson K; Hughes M; Dehghan A; Dedoussis G; Murphy AM; Roche HM; Lehtimaki T; Tanaka T; Liu CT; Ordovas JM; Dupuis J; Franco OH; Uitterlinden A; Lemaitre RN; Deloukas P; Meigs JB; Kahonen M; Rivadeneira F; Voortman T; Hong J; O'Gaorajose P; Follis JL; Marouli E; Murphy LM; Mikkila V; de Mutsert R; Mook-Kanamori DO
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
Lkram MA
Raitakari OT
Noordam R
Smith CE
Richardson K
Hughes M
Dehghan A
Dedoussis G
Murphy AM
Roche HM
Lehtimaki T
Tanaka T
Liu CT
Ordovas JM
Dupuis J
Franco OH
Uitterlinden A
Lemaitre RN
Deloukas P
Meigs JB
Kahonen M
Rivadeneira F
Voortman T
Hong J
O'Gaorajose P
Follis JL
Marouli E
Murphy LM
Mikkila V
de Mutsert R
Mook-Kanamori DO
WILEY
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042821118
https://urn.fi/URN:NBN:fi-fe2021042821118
Tiivistelmä
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-1 beta 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 (beta +/- 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.
Kokoelmat
- Rinnakkaistallenteet [19207]