Blood microRNA patterns distinguish metabolic disease in people of any body weight

Researchers in Qatar have identified circulating microRNA signatures that separate people with metabolic dysfunction from those who are metabolically healthy, regardless of whether they live with obesity or have a normal body weight. The study, published in Diabetology & Metabolic Syndrome, examined plasma samples from 240 Qatari adults.

The team classified participants into four groups of 60 each: metabolically healthy people with obesity, metabolically unhealthy people with obesity, metabolically healthy normal-weight individuals, and metabolically unhealthy normal-weight individuals. This design allowed the investigators to search for molecular markers tied to metabolic health status independent of body mass index.

Differential microRNA expression was assessed using chemometric analyses, followed by target-gene and pathway enrichment analyses. The researchers report that distinct circulating microRNA profiles differentiated the metabolic phenotypes, meaning the patterns in the blood differed between the groups.

Among the key molecules, hsa-miR-122-5p and hsa-miR-195-5p were highlighted as microRNAs that helped distinguish metabolically healthy people with obesity from their metabolically unhealthy counterparts, with additional microRNAs also contributing to the separation between groups.

The pathway analysis pointed to different biological territory depending on the phenotype. Predicted targets of microRNAs associated with metabolically unhealthy obesity were enriched in pathways related to lipid metabolism, insulin signaling, inflammation, oxidative stress, and apoptosis.

In contrast, microRNAs associated with metabolically unhealthy normal weight were linked to a different set of processes: immune regulation, inflammatory signaling, leukocyte migration, and lipid transport. This suggests that metabolic dysfunction in people of normal weight may involve molecular mechanisms that differ from those seen in obesity.

Beyond the individual microRNAs, the study also found that several microRNAs and microRNA ratios showed strong discriminatory performance across the metabolic phenotypes, indicating potential value as biomarkers for identifying metabolic dysfunction in clinical settings.

The authors conclude that circulating microRNA signatures distinguish metabolic health phenotypes independent of BMI and highlight distinct molecular pathways associated with metabolic dysfunction in people with obesity and in people of normal weight. The work is published as an open-access article, and the version currently available is an early, peer-reviewed, accepted manuscript that remains subject to further edits before the final version of record.

The study was conducted by Olfa Khalifa, Neyla S. Al-Akl, Alberto de la Fuente, Khalid Ouararhni, and Abdelilah Arredouani, and published on 15 October 2026. Because the analysis is cross-sectional and based on a single cohort of Qatari adults, the findings describe associations between microRNA profiles and metabolic status rather than establishing causal effects, and further validation in other populations will be needed to confirm their clinical utility.

Subject of Research: Circulating microRNA signatures associated with metabolic health status independent of body mass index in Qatari adults

Article Title: Circulating miRNA signatures reveal metabolic dysfunction beyond obesity

Article References: Khalifa, O., Al-Akl, N. S., de la Fuente, A., Ouararhni, K., & Arredouani, A. (2026). Circulating miRNA signatures reveal metabolic dysfunction beyond obesity. Diabetology & Metabolic Syndrome. https://doi.org/10.1186/s13098-026-02315-9

Image Credits: AI Generated

DOI: 10.1186/s13098-026-02315-9

Keywords: microRNA, metabolic health, obesity, body mass index, biomarkers, insulin signaling, inflammation, lipid metabolism, Qatar, plasma, Diabetology & Metabolic Syndrome, pathway analysis