The glucocorticoid-induced leucine zipper (GILZ) serves as an anti-inflammatory regulator of gene expression in different tissues and is also expressed in human skeletal muscle. GILZ mediates the anti-myogenic and myotoxic side effects of statins via a shift in the Akt/FoxO signaling pathways. Recent evidence suggests that GILZ suppression is regulated by physical exercise, with external load being the decisive factor. Interestingly, statin treatment is rarely tolerated by habitually exercising individuals due to statin-associated muscle symptoms (SAMS). The opposing regulation of GILZ underpins this detrimental interaction of key measures of cardiovascular prevention. This interaction hypothetically differs between diverging exercise modalities in a mechanosensitive manner. To verify emerging evidence, we conducted a systematic search of the Gene Expression Omnibus (GEO) repository for studies reporting the acute effects of either endurance (END), conventional resistance (RT), or eccentric resistance training (ECC). 15 studies with 204 participants (22 females; 182 males, 18 to 90 years of age) were included in the analysis. Participants' activity levels ranged from sedentary to trained. RT resulted in the highest GILZ suppression, significantly differing from the expressional change after END (-0.46 ± 1.11 vs. -0.07 ± 1.08; p = 0.03), but not from ECC (-0.46 ± 1.11 vs. -0.46 ± 0.95; p = 0.19). Furthermore, subgrouping revealed that RT-experienced participants exhibited a more pronounced GILZ suppression than their inexperienced counterparts (-0.98 ± 0.66 vs. -0.34 ± 1.16; p = 0.001). Our results strengthen the assumption that mechanical loading can be considered a key mediator of exercise-induced changes in GILZ expression.

The authors have declared no competing interest.

This study did not receive any funding.

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The study used only openly available human data that were originally located at the Gene Expression Omnibus (GEO) repository [https://www.ncbi.nlm.nih.gov/gds]. Included trials are referenced in the manuscript with the corresponing GEO accession number. Further, data extraction and processing is highlighted in the methods section.

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The data were obtained from the publicly available GEO repository [https://www.ncbi.nlm.nih.gov/gds], included trials are referenced with their respective GEO accession number in Table 1.