F Ramzan1,2, R F D'Souza1, B R Durainayagam1, A M Milan1, J F Markworth1, V Miranda-Soberanis3, I R Sequeira4,5, N C Roy6,2,4,7, S D Poppitt2,4,5, C J Mitchell1,8, D Cameron-Smith9,10,11. 1. Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1142, New Zealand. 2. The Riddet Institute, Massey University, Palmerston North, New Zealand. 3. Department of Statistics, The University of Auckland, Auckland, New Zealand. 4. The High-Value Nutrition National Science Challenge, Auckland, New Zealand. 5. Human Nutrition Unit, Department of Medicine, School of Biological Sciences, The University of Auckland, Auckland, New Zealand. 6. Food Nutrition and Health Team, AgResearch Grasslands, Palmerston North, New Zealand. 7. Food and Bio-Based Products Group, AgResearch Ltd., Palmerston North, New Zealand. 8. School of Kinesiology, The University of British Columbia, Vancouver, Canada. 9. Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1142, New Zealand. d.cameron-smith@auckland.ac.nz. 10. The Riddet Institute, Massey University, Palmerston North, New Zealand. d.cameron-smith@auckland.ac.nz. 11. Food and Bio-Based Products Group, AgResearch Ltd., Palmerston North, New Zealand. d.cameron-smith@auckland.ac.nz.
Abstract
AIMS: Circulatory microRNAs (c-miRNAs) exert important roles in the molecular dysregulation of cardio-metabolic diseases. However, little is known whether dysregulated miRNA expression occurs when risk factors are elevated, as in the metabolic syndrome (MetS). This study quantified c-miRNA expression in individuals with MetS compared to healthy, further examining the relationship of gene pathways with the underlying pathogenesis. METHODS: Expression of 26 miRNAs was quantified in plasma from 40 women (20 healthy and 20 MetS) and 39 men (20 healthy and 19 MetS) by qPCR. In silico analysis was performed to investigate biological effects of the dysregulated miRNAs. Dysregulated miRNA expression was further validated in an independent cohort of 20 women (10 healthy and 10 MetS). RESULTS: Regression model adjusted for age and sex identified miR-15a-5p, miR-17-5p, miR-370-3p and miR-375 as important predictors of MetS presence. Analysis of predictive miRNAs in the validation cohort strengthened the relationship with miR-15a-5p and miR-17-5p expression. These miRNAs share genes involved in the regulation of metabolic pathways including insulin, wnt, fatty acid metabolism and AMPK. CONCLUSIONS: miR-15a-5p and miR-17-5p were identified as predictive biomarkers of MetS, irrespective of sexes, further demonstrating the relationship of c-miRNAs to known pathways of metabolic disturbances present in cardio-metabolic diseases.
AIMS: Circulatory microRNAs (c-miRNAs) exert important roles in the molecular dysregulation of cardio-metabolic diseases. However, little is known whether dysregulated miRNA expression occurs when risk factors are elevated, as in the metabolic syndrome (MetS). This study quantified c-miRNA expression in individuals with MetS compared to healthy, further examining the relationship of gene pathways with the underlying pathogenesis. METHODS: Expression of 26 miRNAs was quantified in plasma from 40 women (20 healthy and 20 MetS) and 39 men (20 healthy and 19 MetS) by qPCR. In silico analysis was performed to investigate biological effects of the dysregulated miRNAs. Dysregulated miRNA expression was further validated in an independent cohort of 20 women (10 healthy and 10 MetS). RESULTS: Regression model adjusted for age and sex identified miR-15a-5p, miR-17-5p, miR-370-3p and miR-375 as important predictors of MetS presence. Analysis of predictive miRNAs in the validation cohort strengthened the relationship with miR-15a-5p and miR-17-5p expression. These miRNAs share genes involved in the regulation of metabolic pathways including insulin, wnt, fatty acid metabolism and AMPK. CONCLUSIONS:miR-15a-5p and miR-17-5p were identified as predictive biomarkers of MetS, irrespective of sexes, further demonstrating the relationship of c-miRNAs to known pathways of metabolic disturbances present in cardio-metabolic diseases.
Authors: Yongxin Li; Yu Meng; Xiangyang Zhu; Andre Van Wijnen; Alfonso Eirin; Lilach O Lerman Journal: Front Endocrinol (Lausanne) Date: 2021-08-12 Impact factor: 5.555
Authors: F Ramzan; R F D'Souza; B R Durainayagam; A M Milan; N C Roy; M C Kruger; C J Henry; C J Mitchell; D Cameron-Smith Journal: Genes Nutr Date: 2020-02-04 Impact factor: 5.523