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Genes Nutr. 2020 Feb 4;15:2. doi: 10.1186/s12263-020-0660-8. eCollection 2020.

Inflexibility of the plasma miRNA response following a high-carbohydrate meal in overweight insulin-resistant women.

Author information

1
1The Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag, 92019, Auckland, 1142 New Zealand.
2
2The Riddet Institute, Palmerston North, New Zealand.
3
3School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
4
4Food Nutrition & Health Team, AgResearch Ltd, Palmerston North, New Zealand.
5
The High-Value Nutrition National Science Challenge, Auckland, New Zealand.
6
6Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.
7
7Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, 117609 Singapore.
8
8School of Kinesiology, The University of British Columbia, Vancouver, Canada.
9
9Food & Bio-Based Products Group, AgResearch Ltd, Palmerston North, New Zealand.
10
10Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (ASTAR), Singapore, 117609 Singapore.

Abstract

Context:

Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs).

Design:

The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women.

Participants:

Age-matched healthy weight IS (n = 20, BMI = 24.3 ± 0.70) and overweight IR (n = 20, BMI = 28.6 ± 0.67) women.

Methods:

An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ; 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs).

Results:

In healthy weight IS women, both miR-15a-5p (p = 0.03) and miR-17-5p (p < 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A (p = 0.01) and IL8 (p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women.

Conclusions:

The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs.

Trial registration:

The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505. Registered on 21 October 2015.

KEYWORDS:

Gene expression; Metabolic inflexibility; Noncoding-RNA; PBMCs; Substrate switching

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

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