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An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: effect of
Donato Santovito1, Velia De Nardis, Pamela Marcantonio
1Geriatric Clinic, European Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, (D.S., V.D.N., P.M., C.M., C.P., E.V., M.B., A.M., F.C.) Clinical Research Center, Center of Excellence on Aging (D.S., V.D.N., P.M., C.M., C.P., M.B., A.M., A.C., F.C.), Center of Predictive Molecular Medicine, Center of Excellence on Aging (F.B.), Diabetes and Metabolism Unit, Department of Medicine and Aging Sciences (A.C.), "G. d'Annunzio" University, 66100 Chieti, Italy; and Institute for Cardiovascular Prevention (D.S.), Ludwig-Maximilians University, 80336 Munich, Germany.
Context:
Type 2 diabetes is a chronic disease characterized by inadequate β-cell response to the progressive insulin resistance. MicroRNAs (miRNAs) are short, endogenous, noncoding RNAs representing a class of powerful gene expression modulators. Previous population studies observed a modulation of circulating miRNAs in diabetic patients; however, few data are presently available on miRNA modulation in diabetic patients naïve to pharmacological treatment as well as the effect of glycemic control on this.
Objective:
We aimed at studying circulating miRNA expression in diabetic patients naïve to treatment and at investigating the influence on this of glycemic control.
Design:
This was a case-control study.
Participants:
Eighteen treatment-naïve diabetic patients with poor metabolic control and 12 control patients participated in the study.
Main Outcome Measures:
Wide miRNA expression profiling was performed, and the expression of miRNAs found to be dysregulated was then validated by quantitative RT-PCR. Finally, algorithm-identified putative miRNA targets were evaluated by quantitative RT-PCR and ELISA.
Results:
In diabetic patients, microarray analysis showed that four miRNAs are increased, whereas 21 miRNAs are decreased. Quantitative RT-PCR validation confirmed the significant up-regulation of miR-326 (P = .004) and down-regulation of let-7a (P < .001) and let-7f (P = .003). Notably, an inverse negative correlation was found between circulating miR-326 and its putative target adiponectin (p = -0.479, P = .009). After 12 months of antidiabetic treatment, quantitative RT-PCR data analysis showed that miR-326 levels were unaffected, whereas the levels of let-7a and let-7f were significantly increased.
Conclusions:
Treatment-naïve, poorly controlled diabetic patients show a significant dysregulation of miRNAs involved in the regulation of the adiponectin pathway, a phenomenon that may be reversed, at least in part, by improved glycemic control.
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