(P04-022-25) Differentially Expressed microRNA between Individuals With Higher and Lower Body Mass Indexes Regulate Inflammatory Pathways Within Skeletal Muscle

Objectives: microRNA (miRNA) are regulators of biological processes governing the expression of mRNA involved in metabolism, anabolism, and catabolism. Whether miRNA profiles differ between adults with a higher or lower body mass index (BMI), and what impact these differences have on their target mRNA regulating skeletal muscle homeostasis is unclear. The objective of this study was to compare miRNA expression profiles in individuals with lower BMI (LOW: 18.5-25 kg/m²) or higher BMI (HIGH: >30 kg/m²) and assess what impact differences may have on mRNA targets within skeletal muscle.

Methods: Twenty-three adults completed this cross-sectional study, of those 12 met the criteria for LOW (BMI: 23.4 ± 3.6 kg/m², age: 21.2 ± 3.1 y, sex: 10 M/2 F) and 11 for HIGH (BMI: 31.3 ± 1.5 kg/m², age: 22.8 ± 3.1 y, sex: 11 M). A single muscle biopsy was conducted in the vastus lateralis under a local anesthetic (1% lidocaine) following a 10-hour overnight fast. Leg lean and fat mass were determined using dual-energy X-ray absorptiometry. Expression of miRNA (Qiagen microarray) and mRNA (Taqman probes) were assessed using RT-qPCR. Bioinformatics (miRTargetLink 2.0) were performed on significant miRNA.

Results: Leg lean mass and fat mass were lower (P < 0.05) in LOW (19.2 ± 2.3 kg, 4.7 ± 1.3 kg, respectively) compared with HIGH (24.0 ± 1.5 kg, 7.6 ± 1.9 kg, respectively). Of the 84 miRNA assessed, six miRNA (let-7f-5p, miR-133b, miR-19a-3p, miR-204-5p, miR-23b-3p, miR-26a-5p, miR-27b-3p, miR-335-5p) were higher (P < 0.05) in LOW compared with HIGH. Assessing targeted mRNA, expression of CXCR4, SMAD4, IL6, IL6R, TGFB1, and PIK3CB were lower (P < 0.05) in LOW compared with HIGH and were all positively associated with leg lean mass (P < 0.05). IL6 and PIK3CB were positively associated with leg fat mass (P < 0.05).

Conclusions: These findings identify differences in miRNA between adults with higher and lower BMI. In individuals with higher BMI, lower expressions of these miRNA results in the higher expression of target mRNA markers of inflammation and are associated with leg lean and fat mass. Overall, these data suggest that divergent miRNA may be a contributing underlying mechanism increasing inflammation in individuals with higher BMI and body fat.

Funding Sources: Supported by USAMRDC. The opinions expressed in this abstract are the author’s own and do not reflect the view of the U.S. Army or DoD policy.