PDE5 inhibition ameliorates visceral adiposity targeting the miR-22 / SIRT1 pathway: evidence from the CECSID trial (original) (raw)

The Journal of clinical endocrinology and metabolism, 2016

Abstract

Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients (T2DM). To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (EAT), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated miRNAs. Randomized, double-blind, placebo-controlled study in T2DM. Patients & Intervention: 59 diabetic patients were randomized to receive 100 mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected. Main Outcomes and Measures: Anthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging (CMR), array of 2005 circulating miRNAs, qPCR and flow cytometry of VAT. Compared to placebo, sildenafil reduced waist circumference (...

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