Location: Jean Mayer Human Nutrition Research Center On Aging
Title: 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 individualsAuthor
MURPHY, AOIFE - University College Dublin | |
SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
MURPHY, LEANE - University College Dublin | |
FOLLIS, JACK - University Of St Thomas | |
TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH) | |
RICHARDSON, KRIS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
NOORDAM, RAYMOND - Leiden University Medical Center | |
LEMAITRE, ROZENN - University Of Washington | |
KAHONEN, MIKA - University Of Tampere | |
DUPUIS, JOSEE - Boston University | |
VOORTMAN, TRUDY - Erasmus Medical Center | |
MAROULI, EIRINI - Queen Mary University Of London | |
MOOK-KANAMORI, DENNIS - Leiden University Medical Center | |
RAITAKARI, OLLI - University Of Turku | |
HONG, JAEYOUNG - Boston University | |
DEHGHAN, ABBAS - Erasmus Medical Center | |
DEDOUSSIS, GEORGE - Harokopio University Of Athens | |
DE MUTSERT, RENEE - Leiden University Medical Center | |
LEHTIMAKI, TERHO - University Of Tampere | |
LIU, CHING-TI - Boston University | |
RIVADENEIRA, FERNANDO - Erasmus Medical Center | |
DELOUKAS, PANAGIOTIS - Queen Mary University Of London | |
MIKKILA, VERA - University Of Helsinki | |
MEIGS, JAMES - Massachusetts General Hospital | |
UITTERLINDEN, ANDRE - Erasmus Medical Center | |
IKRAM, MOHAMMAD - Erasmus Medical Center | |
FRANCO, OSCAR - Erasmus Medical Center | |
HUGHES, MARIA - University College Dublin | |
O'GAORA, PEADAR - University College Dublin | |
ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
ROCHE, HELEN - University College Dublin |
Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 8/20/2019 Publication Date: 11/19/2019 Citation: Murphy, A.M., Smith, C.E., Murphy, L.M., Follis, J.L., Tanaka, T., Richardson, K., Noordam, R., Lemaitre, R.N., Kahonen, M., Dupuis, J., Voortman, T., Marouli, E., Mook-Kanamori, D.O., Raitakari, O.T., Hong, J., Dehghan, A., Dedoussis, G., De Mutsert, R., Lehtimaki, T., Liu, C., Rivadeneira, F., Deloukas, P., Mikkila, V., Meigs, J.B., Uitterlinden, A., Ikram, M.A., Franco, O.H., Hughes, M., O'Gaora, P., Ordovas, J.M., Roche, H.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 and Food Research. 63(22):1900226. https://doi.org/10.1002/mnfr.201900226. DOI: https://doi.org/10.1002/mnfr.201900226 Interpretive Summary: Insulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D), and there is evidence in support that saturated fat consumption may induce both of them. There is a metabolic sensor known as the "nod-like receptor pyrin domain containing-3" (NLRP3) inflammasome, which is activated by saturated fatty acids (SFA) initiating inflammation and IR. Interactions between SFA intake and NLRP3-related genetic variants may modulate the development of T2D. To uncover these relationships, we analyzed data combined from six different cohorts (n = 19 005). Our results reveal that Two NLRP3-related genetic variants showed an interaction with SFA to modulate fasting insulin and in those subjects carrying the genetic variants a higher dietary SFA intake accentuates T2D risk. Technical Abstract: 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-1beta 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. |