A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
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
Tekijät: Murphy AM, Smith CE, Murphy LM, Follis JL, Tanaka T, Richardson K, Noordam R, Lemaitre RN, Kahonen M, Dupuis J, Voortman T, Marouli E, Mook-Kanamori DO, Raitakari OT, Hong J, Dehghan A, Dedoussis G, de Mutsert R, Lehtimaki T, Liu CT, Rivadeneira F, Deloukas P, Mikkila V, Meigs JB, Uitterlinden A, Lkram MA, Franco OH, Hughes M, O'Gaorajose P, Ordovas JM, Roche HM, Roche HM
Kustantaja: WILEY
Julkaisuvuosi: 2019
Journal: Molecular Nutrition and Food Research
Tietokannassa oleva lehden nimi: MOLECULAR NUTRITION & FOOD RESEARCH
Lehden akronyymi: MOL NUTR FOOD RES
Artikkelin numero: ARTN 1900226
Vuosikerta: 63
Numero: 22
Sivujen määrä: 9
ISSN: 1613-4125
DOI: https://doi.org/10.1002/mnfr.201900226
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/42517263
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
