Serum miR-365b-5p/miR-222-5p as a potential diagnostic biomarker for long-term weight loss in patients with morbid obesity after bariatric surgery

Abstract

Background

The successful weight loss following bariatric surgery is not achieved in all patients with morbid obesity (MO). This study aims to determine whether a serum miRNA profile can predict this outcome.

Design

Thirty-three patients with MO were classified in “Good Responders” (GR, percentage of excess weight loss (%EWL) ≥ 50 %) or “Non-Responders” (NR, %EWL < 50 %) according to the %EWL 5–8 year following bariatric surgery. Baseline serum miRNA sequencing was performed to find predictor biomarkers and human adipocyte culture were performed to determine their effect.

Results

Fifty-six differentially expressed miRNAs were found between GR and NR. Logistic regression models showed two miRNAs, hsa-miR-365b-5p (upregulated in GR) and hsa-miR-222-5p (upregulated in NR) associated to %EWL. Receiver operating characteristic curves showed that the combination of these miRNAs was the best serum miRNAs profile that distinguished between GR and NR. The experimentally validated target genes of these miRNAs were involved in processes related to the response to stress, cell cycle, transduction, and development and proliferation processes. The in vitro expression of six genes involved in adipogenesis and adipocyte differentiation (STAT3, ILR7, PARP1, SOD2, FGF2 and TMEM18) was downregulated in lipogenic and upregulated in lipolitic conditions in human adipocytes incubated with the combination of a hsa-miR-365b-5p mimic and a hsa-miR-222-5p inhibitor.

Conclusions

Baseline serum hsa-miR-365b-5p and hsa-miR-222-5p were able to predict %EWL 5–8 years following bariatric surgery. The combination of these potential predictive biomarkers was involved in regulating the expression levels of genes associated with obesity. However, these effects could be modified depending of other stimuli.