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Changes in Circulating MicroRNA Profiles During Arctic Military Training Target Inflammatory Pathways Independent of
Lee M Margolis1, Hilde K Teien2, Adrienne Hatch-McChesney1
1Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States.
Background:
Circulating microRNA (c-miRNA) are sensitive to exercise, energy status, and macronutrient intake, and facilitate adaptations to physiological stress. Whether changes in c-miRNA during Arctic military training differ based on macronutrient intake and if such differences alter their regulatory function is unknown.
Objectives:
This study aimed to determine whether consuming essential amino acid (EAA)-dense (EAA-dense), high-fat energy-dense (EN-dense), or high-carbohydrate (CHO) supplemental nutrition daily during Arctic military training affected c-miRNA.
Methods:
Soldiers participating in an 8-d Arctic military training were randomly assigned to receive 3 standard rations plus 4 EAA-dense (n = 27; 31g protein), EN-dense (n = 22; 35 g fat), or CHO (n = 19; 70 g carbohydrate) snack bars providing ∼5000 kcal/d. Macronutrient intake (wrapper/food waste collection) was assessed daily. c-miRNA were measured using qRT-PCR pretraining and posttraining. Bioinformatics and in vitro analysis were used to identify function of the c-miRNA, with the most significant fold change from pretraining to posttraining.
Results:
There was no difference in energy intake, although protein, fat, and carbohydrate intakes were highest (P < 0.05) in EAA-dense, EN-dense and CHO, respectively. Whether participants consumed the EAA-dense, EN-dense, or CHO snack bars during 8-d training had no effect on c-miRNA profiles. Twenty-six c-miRNA changed (24 decreased and 2 increased; P < 0.05) from pretraining to posttraining, independent of treatment. miR-146a-5p exhibited the most robust change from pretraining to posttraining and was identified to target inflammatory signaling. In vitro overexpression of miR-146a-5p in C2C12 myoblasts reduced (P < 0.05) Il6, Tnfα, and Traf6 gene expression and suppressed inflammatory responses within cells.
Conclusions:
In summary, miR-146a-5p is a potential regulator of the inflammatory response to physiological stress, independent of dietary macronutrient composition. This trial was registered at www.
Clinicaltrials:
gov as NCT05210205 (https://clinicaltrials.gov/study/NCT05210205).
Insights
Arctic military training impacts circulating microRNA (c-miRNA) profiles, independent of macronutrient intake. MiR-146a-5p emerges as a key regulator of inflammatory responses to physiological stress.
Area of Science:
- Exercise physiology
- Molecular biology
- Nutritional science
Background:
- Circulating microRNAs (c-miRNAs) are responsive to physiological stressors like exercise and energy status.
- Understanding c-miRNA changes during intense training and their modulation by diet is crucial for optimizing performance and health.
- The specific impact of varying macronutrient intake on c-miRNA during Arctic military training remains unexplored.
Purpose of the Study:
- To investigate the effect of essential amino acid-dense (EAA-Dense), energy-dense high-fat (EN-Dense), and high-carbohydrate (CHO) supplemental nutrition on c-miRNA profiles during Arctic military training.
- To determine if dietary macronutrient composition influences the regulatory function of c-miRNAs in response to extreme environmental conditions and physical exertion.
Main Methods:
- Soldiers underwent an 8-day Arctic training regimen, receiving standard rations plus one of three supplemental snack bars (EAA-Dense, EN-Dense, or CHO).
- Macronutrient intake was meticulously tracked daily. Circulating microRNAs (c-miRNAs) were quantified using RT-qPCR before and after training.
- Bioinformatics and in vitro analyses identified the functional role of significantly altered c-miRNAs, focusing on miR-146a-5p.
Main Results:
- No significant differences in overall energy intake were observed across groups.
- While specific macronutrient intakes varied as intended (highest protein in EAA-Dense, fat in EN-Dense, carbohydrate in CHO), the type of supplemental nutrition did not alter c-miRNA profiles.
- Twenty-six c-miRNAs showed significant changes from pre- to post-training, irrespective of the dietary intervention. MiR-146a-5p demonstrated the most pronounced change and was found to target inflammatory signaling pathways.
Conclusions:
- MiR-146a-5p plays a significant role in regulating inflammatory responses to physiological stress during intense training.
- Dietary macronutrient composition, within the tested parameters, did not influence the observed changes in c-miRNA profiles or the function of miR-146a-5p.
- This study identifies miR-146a-5p as a potential biomarker and therapeutic target for managing inflammation in physically stressed individuals.
