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

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 ( = 20, BMI = 24.3 ± 0.70) and overweight IR ( = 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 ( = 0.03) and miR-17-5p ( < 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, ( = 0.01) and ( = 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.