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

Autor: Ching-Ti Liu, Leanne M Murphy, Fernando Rivadeneira, Peadar Ó Gaora, Jose M. Ordovas, George Dedoussis, Renée de Mutsert, Abbas Dehghan, Aoife M. Murphy, Caren E. Smith, Jack L. Follis, Raymond Noordam, Terho Lehtimäki, André G. Uitterlinden, Rozenn N. Lemaitre, Panagiotis Deloukas, Mika Kähönen, Dennis O. Mook-Kanamori, Jaeyoung Hong, Vera Mikkilä, Oscar H. Franco, Trudy Voortman, Kris Richardson, Olli T. Raitakari, Mohammad Arfan Ikram, Maria Hughes, James B. Meigs, Eirini Marouli, Toshiko Tanaka, Helen M. Roche, Josée Dupuis
Přispěvatelé: Science Foundation Ireland, Epidemiology, Internal Medicine
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
medicine.medical_specialty
Diabetes risk
Inflammasomes
medicine.medical_treatment
Single-nucleotide polymorphism
Type 2 diabetes
Biology
Pyrin domain
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Cohorts for Heart and Ageing Research in Genomic Epidemiology consortium
Insulin resistance
SDG 3 - Good Health and Well-being
Internal medicine
insulin resistance
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Humans
Allele
saturated fats
030109 nutrition & dietetics
Insulin
Genetic Variation
food and beverages
Inflammasome
medicine.disease
Dietary Fats
Genome-wide interaction studies
030104 developmental biology
Endocrinology
Saturated fats
Diabetes Mellitus
Type 2
meta-analyses
Meta-analyses
NLRP3 inflammasomes
genome-wide interaction studies
Food Science
Biotechnology
medicine.drug
Zdroj: Molecular Nutrition and Food Research, 63(22). WILEY
Molecular Nutrition & Food Research, 63(22). Wiley-VCH
Repisalud
Instituto de Salud Carlos III (ISCIII)
ISSN: 1613-4125
Popis: 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.
Databáze: OpenAIRE
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