Decreased miR-181a expression in monocytes of obese patients is associated with the occurrence of metabolic syndrome and coronary artery disease.

Abstract

CONTEXT:

Inflammation during obesity is associated with higher risk of metabolic syndrome and coronary artery disease (CAD). Activation of the inflammatory toll-like receptor (TLR)/nuclear factor κB (NFκB) signaling in monocytes contributes to inflammation. Weight loss after bariatric surgery leads to significant improvement of obesity-related comorbidities. MicroRNA (miR), a class of small noncoding RNA, have been implicated as negative regulators of inflammatory processes.

OBJECTIVE:

This study sought to identify dysregulated miR in monocytes of obese patients associated with TLR/NFκB signaling, metabolic syndrome, and CAD.

DESIGN, SETTING, AND PATIENTS:

This retrospective study included two independent cohorts of 21 morbidly obese and 125 high-risk obese and nonobese patients in a hospitalized care setting.

INTERVENTION:

INTERVENTION included bariatric surgery (n = 21) with a 3-month follow-up.

MAIN OUTCOME MEASURES:

miR expressions in CD14(+) monocytes were determined by microarray analysis. TLR/NFκB-related miR were identified by an in silico target prediction analysis. Their expression was validated by quantitative RT-PCR. Their association with metabolic syndrome and angiographically documented CAD was assessed.

RESULTS:

miR-181a, -181b, and -181d, identified as possible regulators of the TLR/NFκB signaling, were decreased in obese monocytes, and weight loss normalized their expression to levels observed in monocytes of lean persons. miR-181a but not miR-181b and miR-181d was associated with a higher number of metabolic syndrome components and with CAD even after adjustment for traditional risk factors, obesity and the metabolic syndrome.

CONCLUSION:

This study demonstrates that the TLR/NFκB-related miR-181a is down-regulated in monocytes of obese patients and suggests that it is a putative biomarker of metabolic syndrome and CAD.

• Authors: Maarten Hulsmans, Peter Sinnaeve, Bart Van der Schueren, Chantal Mathieu, Stefan Janssens, Paul Holvoet
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 97 Issue 7 Pg. E1213-8 (Jul 2012) ISSN: 1945-7197 [Electronic] United States
• PMID: 22535975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIrn181 microRNA, human
• MicroRNAs

Topics

• Adult
• Bariatric Surgery (rehabilitation)
• Case-Control Studies
• Cohort Studies
• Comorbidity
• Coronary Artery Disease (complications, epidemiology, genetics, pathology)
• Down-Regulation (genetics)
• Female
• Follow-Up Studies
• Gene Expression Regulation
• Humans
• Incidence
• Male
• Metabolic Syndrome (complications, epidemiology, genetics, pathology)
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Monocytes (metabolism, pathology)
• Obesity (epidemiology, genetics, pathology, surgery)
• Retrospective Studies
• Validation Studies as Topic