Altered miR-30c and miR-127 expression and NF-κB/NLRP3-related transcriptional changes are associated with metabolic and inflammatory dysregulation in adult males with sleep deprivation and habitual coffee consumption

Abstract Background Chronic sleep deprivation and habitual coffee consumption are common overlapping behaviours, yet the post-transcriptional expression patterns associated with their metabolic and inflammatory correlates remain poorly defined. This study examined alterations in the regulatory microRNAs miR-30c and miR-127 and transcript-level expression changes consistent with involvement of the NF-κB/NLRP3 inflammatory axis, together with their metabolic and inflammatory correlates, in adult males. Methods Two hundred male volunteers aged 30–50 years were classified into four groups of 50 according to sleep pattern and coffee intake: healthy controls (HC; normal sleep, no habitual coffee consumption), habitual coffee consumers (CF), sleep-deprived subjects (SD), and a combined sleep-deprived, coffee-consuming group (SD + CF). Expression of miR-30c, miR-127, NLRP3, and NF-κB p65 (RELA) was assessed by quantitative real-time PCR. Fasting glucose was measured by the glucose oxidase method, the lipid profile by enzymatic colorimetry, and serum IL-6, IL-1β, TNF-α, and IL-10 by ELISA. Results Compared with healthy controls, the SD + CF group showed marked downregulation of miR-30c and miR-127 and pronounced upregulation of NLRP3 mRNA (all p < 0.001), accompanied by increased NF-κB p65 expression (3.79-fold; p < 0.001). These molecular changes were paralleled by significantly elevated IL-6, IL-1β, and TNF-α and reduced IL-10, as well as higher fasting glucose (108.5 ± 12.3 vs. 89.2 ± 8.6 mg/dL; p < 0.001), total cholesterol, LDL-cholesterol, and triglycerides, with reduced HDL-cholesterol (all p < 0.05). In pairwise comparisons, the CF group differed significantly from HC only in fasting glucose, whereas the combined SD + CF group showed the most pronounced metabolic, inflammatory, and molecular alterations. Two-way factorial analysis identified significant Sleep × Coffee interactions for LDL-cholesterol, triglycerides, IL-6, IL-1β, TNF-α, NF-κB p65, miR-30c, miR-127, and NLRP3. Conclusions Chronic sleep deprivation, particularly when accompanied by habitual coffee consumption, is associated with altered miR-30c and miR-127 expression and an expression pattern consistent with involvement of the NF-κB/NLRP3 axis, alongside metabolic and inflammatory dysregulation in adult males, with statistical evidence of a combined, potentiating association between the two exposures for several inflammatory and molecular outcomes. These findings add a post-transcriptional dimension to the understanding of how insufficient sleep and habitual coffee consumption relate to cardiometabolic risk.